Evaluation of rice palatability.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"1536",leadTitle:null,fullTitle:"Material Recycling - Trends and Perspectives",title:"Material Recycling",subtitle:"Trends and Perspectives",reviewType:"peer-reviewed",abstract:"The presently common practice of wastes' land-filling is undesirable due to legislation pressures, rising costs and the poor biodegradability of commonly used materials. 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Patients are demanding better treatment for a variety of spinal disorders. Patients expect faster recoveries, better outcomes, and techniques and technologies for treating spinal disorders that reduce surgical complications and post-operative pain. Minimally invasive spinal procedures work to limit damage to normal anatomical structures of the spine that can achieve patients' goals to quick recovery and better outcomes. Surgeons wish to learn minimally invasive spinal techniques and technologies that improve patient outcomes.
\r\n\r\n\tThis book will focus on innovative techniques and technologies that can be used to improve patient outcomes and have been developed by minimally invasive spine experts. The textbook is well illustrated with the inclusion of a variety of cases. These cases will be presented to show pre-operative patient evaluation and radiographic studies, rational to technique and technology selected intra-operative images, and post-operative images and patient outcomes. It is hoped that this technique will instruct patients and surgeons as to the best operative minimally invasive procedures to achieve optimal clinical outcomes.
",isbn:"978-1-83962-302-8",printIsbn:"978-1-83962-301-1",pdfIsbn:"978-1-83962-303-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"b6658fda99691e4942e550fb04dc3f8d",bookSignature:"Prof. Mick Perez-Cruet",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10634.jpg",keywords:"Minimally Invasive, Spine, Fusion, Improved Outcomes, Patient Outcomes, Quality of Life, Fast Recovery, Fusion Rates, Case Review, Radiographic Images, Patient Selection, Pre-Operative Workup",numberOfDownloads:1336,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:3,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 10th 2020",dateEndSecondStepPublish:"October 8th 2020",dateEndThirdStepPublish:"December 7th 2020",dateEndFourthStepPublish:"February 25th 2021",dateEndFifthStepPublish:"April 26th 2021",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 years",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Perez-Cruet is an internationally recognized pioneer in minimally invasive spine surgery. He is Vice-Chairman and Professor of the Department of Neurosurgery, Oakland University William Beaumont, School of Medicine, Royal Oak, MI. He has served as the Michigan delegate to the Council of State Neurosurgical Societies (CSNS) for 20 years, was president of the Michigan Association of Neurological Surgeons (MANS), and holds several administrative positions within Beaumont.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"62623",title:"Prof.",name:"Mick",middleName:null,surname:"Perez-Cruet",slug:"mick-perez-cruet",fullName:"Mick Perez-Cruet",profilePictureURL:"https://mts.intechopen.com/storage/users/62623/images/system/62623.jpg",biography:"Dr. Mick Perez-Cruet is an internationally recognized pioneer in the treatment of spinal disorders using minimally invasive surgical techniques. His experience spans more than thirty years. He is vice chairman and professor of the Department of Neurosurgery, Oakland University William Beaumont School of Medicine, MI. He is one of the core faculty for the recently established ACGME Neurosurgery Residency Program at the same university. He is the Beaumont Neurosurgeon Champion for the Michigan Spine Surgery Improvement Collaborative (MSSIC), which is the largest comprehensive spine surgery outcome registry in the country. He dedicates much of his time to teaching neurosurgeons, fellows, residents, and medical students. He has served as the Michigan delegate to the Council of State Neurosurgical Societies (CSNS) for more than twenty years, was president of the Michigan Association of Neurological Surgeons (MANS), and holds several administrative positions within Beaumont. 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Rice consumers need sufficient quantities and high‐quality rice grains.
\nThe rice quality depends on various aspects such as consumer safety, nutrition, appearance, price level, and palatability. Because rice is eaten every day, it is indispensable that it should be safe to eat and highly nutritious. Furthermore, because rice provides income for farmers and is prepared, milled, and sold by wholesalers and retailers, the rice yield and price are extremely important to the farmers. Consumers have been asking for more palatable rice because they have recently become more affluent. According to the Food Agency, 45.1% consumers purchase rice grains based on their palatability, 16.3% select it on the basis of its brand name, and 4.8% choose it on the basis of the location of rice production, implying that more than 66% Japanese consumers prefer palatable rice grains to cheaper, nonpalatable rice.
\nQuality evaluations of rice in Japan are performed by sensory testing and physicochemical measurements. The former is a basic method that requires large amounts of samples and several panelists. The latter is an indirect method that estimates the eating quality based on the chemical compositions, cooking quality, gelatinization properties, and physical properties of cooked rice.
\nA rapid, simple, and more accurate method is required to evaluate rice. Therefore, if a novel method that used near‐infrared spectroscopy could be developed, producers and consumers would have a rapid and nondestructive testing method which assessed the quality of the rice grains.
Sensory testing is the fundamental method that evaluates the eating quality of rice grains. The members of a trained panel taste cooked rice samples and give scores on the basis of appearance, flavor, taste, hardness, stickiness, and overall sensory evaluation. The test results can be expressed as numerical values and treated statistically; there are disadvantages to using this test. The results differ depending on the preference of panel members, and the results cannot be directly compared if the time or country differs.
Physicochemical evaluation [1] is only indirect evaluation of rice palatability, and its results are common all over the world if we use the same method and apparatus. Physicochemical measurements include component analysis, such as protein, amylose, and fibers, pasting properties of starch, texture measurements of the cooked rice grains, etc. For the sake of estimating the total palatability, statistical treatment is adopted using the results of each measurement as the variables. Multiple regression analysis, principal component analysis, and PLS analysis are very useful to clarify the characteristics of the rice samples. Recently, spectrophotometric analyses, such as NIR or visible‐light spectrometer, are utilized to estimate the chemical components and to develop the estimation formulae for palatability. “Taste Analyzer” is an example of the NIR system as a nondestructive estimation apparatus for palatability of rice grains. Examples of sensory test and physicochemical evaluation of rice palatability are shown in Table 1.
Sensory test | Physicochemical test |
---|---|
Appearance | Gloss meter, “Mido” meter |
Aroma | GC, GCMS, Electric nose |
Taste | HPLC, Enzyme kit, Taste sensor, Taste analyzer |
Texture | Texturometer, Texture analyzer, Tensipresser |
Overall evaluation | Multivariate analysis |
Evaluation of rice palatability.
Amylose content is the most important factor that determines rice quality because starch shares approximately 85% (w/w, dry basis) of the milled rice grains. Because Japanese consumers prefer soft and sticky cooked rice, low amylose rice is the dominant rice sold in the Japanese rice market. Amylose content is generally measured by the colorimetric method of Juliano [2].
Protein content is another extremely important factor that determines rice quality. Cooked rice with high protein content tends to be hard and nonsticky. Protein content is measured by the Kieldahl or the combustion method.
Moisture content affects the eating quality of cooked rice. Low‐moisture rice grains absorb water faster than high‐moisture grains. In cooked rice, the final moisture content from the low‐moisture rice grains is higher than that from the high‐moisture rice grains. Moisture content is generally measured by the oven dry method.
The maximum viscosity, final viscosity, and “break‐down” viscosity (maximum viscosity‐minimum viscosity) are measured in an Amylograph. These viscosity measurements were considered good indices for the eating quality of rice. The Rapid‐Visco‐Analyzer (RVA) was developed in Australia and was recently introduced in Japan (Figure 1) [3]. Time (13–19 min) and samples (3.5 g) can be saved using an RVA.
Rapid visco analyzer.
Fat acidity is a good index to measure the quality deterioration of rice grains during storage. In Japan, newly harvested rice is preferred to aged rice because consumers like soft and sticky cooked rice. Ohtsubo proposed a new colorimetric method to accurately measure fat acidity [4].
A cooking quality test was developed by the researchers of USDA in the 1950s [5]. An expanded volume and water uptake ratios are measured after cooking rice samples in excess amounts of water. Dissolved amylose is measured by color generation by combining iodine and amylose.
Physical properties of cooked rice grains, such as hardness and stickiness, are measured by a Texturometer, Tensipresser, Texture analyzer, or Rheolograph‐micro. Low‐compression and high‐compression test using a Tensipresser [6] is shown in Figure 2.
Tensipresser used for texture measurement of cooked rice grains.
Chikubu et al. developed a new equation to estimate the palatability of rice grains using a multiple regression analysis based on physicochemical measurements, such as an amylograph viscosity profile, protein assay, and iodine blue value measurements [7]. The formula showed a high correlation between the results of a sensory test (
Near‐infrared spectroscopy is a rapid, nondestructive, and extremely promising technique to evaluate qualities of the rice grains. In Japan, NIR spectroscopy was initially used to determine the protein and moisture content of the rice flours. Satake Co. Ltd subsequently combined NIR and palatability estimation formula and developed a new system called “Taste Analyzer.”
\nIwamoto et al. reported that NIR was equally sensitive to both rice and wheat proteins. A standard error of estimation (SEP) was decreased for calibrations using a derivative absorbance. However, the derivative procedure may possibly make an increment bias in cases that predict “unknown” samples [8]. Inatsu utilized NIR spectroscopy to select palatable rice cultivars by measuring the protein content of rice because low protein rice is preferred in Japan because of their palatability [9].
Japanese rice breeders have tried to develop palatable rice cultivars by selecting low amylose rice; however, the amylose content among Japanese rice grains are not significantly different (15–20%). NIR spectroscopy can easily compare protein and moisture; however, it does not easily differentiate amylose from amylopectin. Villareal and Delwiche had already developed excellent calibrations to detect amylose in various rice samples through NIR spectroscopy [11, 12]. Japanese consumers request high‐performance calibration for the measurement of narrow range amylose of Japanese rice cultivars. Apparent amylose content (AAC) analysis is a rapid and simple technique that uses NIT spectroscopy. It was developed based on the near-infrared transmission spectra and the reference value of AAC determined by the iodine colorimetric method. The wide AAC range (0–35.3%) PLS model was inadequate for the accurate prediction of the extremely narrow range of the AAC (13.2–20.7%) of Japanese milled rice samples. The statistics performed on the 11‐factor PLS model for the extremely narrow range of AAC analyses was 0.78, 0.74, and 2.01 in SECv, r2, and RPD, respectively. The performance of this model was 1.25 and 0.49 for SEP and r², respectively, on the validation set. The previous models developed a wide range of AAC samples, which were difficult to apply to the narrow range of AAC rice. The present AAC analysis technique is based on NIT spectroscopy, which can discriminate between the extremely narrow differences in AAC of Japanese milled rice in the same subfamily.
Satake Co. Ltd. developed a taste analyzer in the 1980s that combined the palatability estimation formula that was based on the physicochemical measurements and NIR. The taste analyzer principle is based on the multiple regression analysis that uses NIR data (protein, moisture, amylose, and fat acidity) against the sensory test results. A previous study by the Japanese Association of Milling Companies evaluated three different types of palatability evaluation system using NIR. The results showed that the taste scores correlated significantly with the results of the sensory test (
There were eight Japanese companies that developed the characteristic systems to evaluate the palatability of rice grains based on the spectroscopic technique. More than 1000 agricultural cooperatives, wholesalers, and retailers introduced these NIR systems to evaluate the quality of their rice grains (Figure 3). In 1996, the Japanese Food Agency conducted a survey regarding the palatability evaluation system, and the results showed that 67% users were satisfied with the performance of the system. The protein and moisture data was extremely reliable, but some users requested an improvement in the taste score and amylose accuracy.
Taste analyzer based upon NIR technology.
As described in Section 3, physicochemical test is very important because it is time‐saving and labor‐saving objective test for rice palatability. Main component of rice grains is starch, therefore, amylose content affects eating quality [15]. Low‐amylose rice generally becomes soft and sticky after cooking, whereas high‐amylose rice becomes hard with fluffy separated grains [16].
\nThe most widely used method for amylose determination is a colorimetric assay where iodine binds with amylose to produce a blue‐purple color, which is measured spectrophotometrically at a single wavelength (620 nm) [2].
\nWe here characterized the starch of various rice cultivars; evaluated the relationship between their iodine absorption curve and apparent amylose contents, amylopectin fractions, and resistant starch. We improved the iodine colorimetric method, and developed the novel estimation formulae against the amylose contents, resistant starch, or a certain fractions of definite chain‐length amylopectin. This novel method would lead to an easy and low‐cost spectroscopic method for analyses of starch characteristics.
We used Japonica rice, Iindica rice, Indica‐Japonica hybrid rice,
We polished brown rice to a milling yield of 90–91%, using an experimental friction‐type rice milling machine (Yamamotoseisakusyo, Co. Ltd., Tendoh, Japan). White rice flour was produced with a cyclone mill (SFC‐S1; Udy, Fort Collins, CO, USA). Starch granules were prepared from polished rice flour using the cold alkali method.
\nThe iodine absorption spectrum of the rice starch was measured using a Shimadzu UV‐1800 spectrophotometer. The AAC of rice starch was measured by the iodine colorimetric method of Juliano [2]. The iodine absorption spectrum was scanned from 200 to 900 nm. The absorbance was measured at 620 nm, at
Analysis of iodine absorption curve of various starch samples.
The area of F1 (from B to 400 nm), area of F2 (from 400 nm to
We developed a formula for apparent amylose content based on iodine colorimetric analysis. Estimation formula is as follows:
\nChain length distribution (CD) was carried out by the method of Hanashiro et al. using HPAEC‐PAD of isoamylase‐debranched materials of starch:
\nRS in the starch of rice flour was measured according to the AOAC method using a RS assay kit (Megazyme, Wicklow, Ireland) in which each sample (100 mg) was digested by pancreatin and amyloglucosidase at 37°C for 6 h, followed by the measurement of glucose at 510 nm:
\nFraction of DP10 (short chain glucans of amylopectin) and fraction of DP22 (medium chain glucans of amylopectin) were estimated based on F2 area and
Estimation of fraction DP10 and fraction DP22 based on iodine colorimetric analyses.
\n
We found that the iodine absorption curve differed between the Indica rice, Japonica rice, Japonica‐Indica hybrid rice,
We propose a novel index, “new
We developed the novel estimation formulae for AAC, RS contents, amylopectin chain lengths (Fa; DP ≦ 12, Fb3; DP≦ 37), and fraction of DP10 (short chain glucans of amylopectin) and fraction of DP22 (medium chain glucans of amylopectin) on the basis of the iodine absorption curve. These formulae would lead to an easy and low‐cost spectroscopic method for the starch characteristics.
As described in Section 3, in the case of physicochemical evaluation, we can get the common results for the rice samples produced in different countries if we use the same method. As an example, we report the results of physicochemical measurements of rice palatability using rice samples produced in Japan and China.
\nChina is the largest rice‐producing country, accounting for 32% of the global production from 20% of the global rice‐growing area. China produces Indica subspecies mainly in the southern region and Japonica subspecies mainly in the northern region (Heilongjiang, Liaoning), and eastern or southern region (Jilin, Jiangsu, Zhejiang, and Yunnan), whereas the other three countries, India, Indonesia, and Bangladesh, primarily grow Indica rice. In China, consumers are now choosing Japonica rice based on its shape and color as well as its texture and taste. Zhang et al. performed a sensory test of Chinese Japonica rice cultivars [17], in which a Chinese panel mainly determined the overall eating quality based on the stickiness and hardness. In the present section, we conducted physicochemical evaluations of some Chinese and Japanese Japonica rice cultivars using traditional and novel indicators based on the iodine absorption curve and RVA.
We used high‐quality premium Japanese Japonica rice (Koshihikari, Tsuyahime, Yumepirika, Sagabiyori, and Kinumusume) and Chinese Japonica rice cultivars (Kenjing 5, Shendao 529, Jinyuan 45, Changyou 5, Lianjing 7, Longjing 31, Nanjing 9108, Jinongda 878, Shennong 265, Daohuaxiang, and Jinchuan 1) as rice samples.
\nThe moisture content of the milled rice grains was measured using an oven‐drying method by drying 2 g flour samples for 1 h at 135°C.
Nitrogen was determined using a nitrogen analyzer based on the combustion method. The protein content was obtained by multiplying a nitrogen‐protein conversion factor of 5.95.
The iodine absorption spectrum of milled rice was measured using a Shimadzu UV‐1800 spectrophotometer. The apparent amylose content (AAC) of milled rice was estimated using the iodine colorimetric method (as described by Juliano [2]). The iodine absorption spectrum [14] was analyzed from 200 to 900 nm using a square cell of which inner dimension was 1 cm × 1 cm.
The pasting properties of starch rice flours were analyzed using an RVA (model Super 4; Newport Scientific Pty Ltd, Warriewood, Australia). A programmed heating and cooling condition was followed as described by Toyoshima et al. [3]. Novel indices, such as the setback/consistency (SB/Con) and maximum viscosity/minimum viscosity (Max/Fin) ratios, have very strong correlations with the proportion of intermediate and long chains of amylopectin: Fb1 + 2 + 3 (DP≧ 13) [14].
The boiled rice samples were kept in the vessel at 25°C for 2 h and then subjected to the measurements. The hardness and stickiness of the boiled rice grains were measured using a Tensipresser (My Boy System, Taketomo Electric Co., Tokyo, Japan) using “low compression (25%) and high compression (90%) test” [6]. The average of each parameter was calculated by measuring 20 individual grains. As a staling test of the cooked rice, the cooked samples were stored at 10°C for 16 h and measured again with a Tensipresser according to the previously described method [6].
Proteins were extracted from milled rice flour samples (0.5 g) by shaking with 2 mL of buffer A (50 mM Tris‐HCl, pH 6.8, 2% SDS, 5% 2‐mercaptoethanol) at 37°C for 30 min and then centrifuged for 5 min at 3000 ×
Protein is a very important component of milled rice, and it affects the physical properties of cooked rice grains. Higher protein content makes the rice grains harder and less sticky. The protein content of milled Japonica rice is around 6.5%. The protein contents of Chinese rice cultivars (6.8–9.0%; mean = 7.8%) were significantly higher than those of Japanese rice varieties (6.2–6.8%; mean = 6.5%).
\nAAC has been used as a good parameter for estimating the cooking or eating quality of rice grains, and the iodine colorimetric method for AAC measurement at 620 nm was developed by Juliano [2]. AAC comprises a large amount of amylose and a small amount of SLC in amylopectin. In general, low amylose rice becomes soft and sticky after cooking, whereas high amylose rice becomes hard and separated. The AAC values for Chinese rice cultivars (6.6–17.2%; mean = 14.3%) were higher than those of Japanese rice cultivars (9.7–14.6%; mean = 12.7%). In our previous study [14], we showed that the iodine absorption curve differed among various samples of rice cultivars, and we developed a novel formula for estimating AAC. (AAC = 73.31 ×
The molecular structures of many starches, including the molecular sizes of amylose and the amylopectin branch chain lengths, have been reported previously [19–22]. The high molecular weight amyloses tend to have a longer wavelength for
The “new
The starches in the rice cultivars grown under low temperatures have a significantly higher amylose contents than those of the rice cultivars grown under high temperature, whereas the SLC contents of the amylopectin were lower [23–27]. Thus, we consider that the starch properties of Japanese rice cultivars were influenced by the ambient temperatures during the development of the grain, which yielded high “new
There were differences in the values of physical properties of the cooked rice grains. The balance of -H1/H1, -H2/H2, A3/A1, and A6/A4 are important indices when evaluating the palatability of rice [16].
\nThe hardness of the surface layer (H1) was higher in the Chinese rice cultivars than the Japanese rice varieties, and the hardness of the overall layer (H2) of Chinese rice cultivars was higher than that of the Japanese rice varieties. The stickiness of the surface layer (-H1) was significantly lower in the Chinese rice cultivars than the Japanese rice cultivars, whereas the stickiness of overall layer (-H2) was higher in the Chinese rice varieties than the Japanese rice cultivars. The balance degree of the surface layer (-H1/H1) was significantly lower in the Chinese rice varieties than the Japanese rice varieties, and that of the surface layer (A3/A1) was significantly lower in the Chinese rice varieties than the Japanese rice varieties.
\nLow amylose rice cultivars are stale‐resistant according to Takami et al., who previously reported the staling characteristics of cooked low amylose rice [28]. In the staling test, we stored the cooked rice at 10°C for 16 h (Figure 6). The staling rate for starch based on the surface layer hardness (H1) was significantly higher in the Chinese rice cultivars than the Japanese rice cultivars. In particularly, Jinongda 878 (2.3 times), Daohuaxiang (1.9 times), and Nanjing 9108 (1.9 times) had very high values. The staling rates for starch based on the hardness of the overall layer (H2) were almost the same in the Chinese and Japanese rice cultivars. The staling rate for starch based on the hardness of the surface layer (H1) in Chinese rice varieties had a positive correlation with the intensities of the 13 kDa prolamin spots and the protein content at
Results of the staling starch test of the physical properties of cooked rice grains.
The intensities of the bands of 13 kDa prolamin were correlated positively with
The rice seed storage proteins mainly comprise glutelins and prolamins. PB‐I is highly enriched with prolamin and it constitutes approximately 20% of the milled rice protein contents. PB‐II mainly contains glutelins and it constitutes 60–65% of the milled rice protein [29]. The protein content of rice grains is influenced by the weather conditions, as it is increased by high air temperature or high water temperature, but decreased by low water temperature or sun shading during the ripening stage [30]. Matsui et al. [31] showed that the Final vis. and Cons values of near‐isogenic line pairs for the low glutelin gene (
In this study, we evaluated 16 Japanese and Chinese rice cultivars in terms of their main chemical components, iodine absorption curve, apparent amylose content (AAC), pasting property, resistant starch content, physical properties, and SDS‐PAGE.
\nBased on these quality evaluations, we can conclude that Chinese rice cultivars are characterized by their high protein content. The hardness of the surface layer (H1) and overall layer (H2) were higher in the Chinese rice cultivars than the Japanese rice cultivars, whereas the stickiness of the surface layer, and the balance degree of the surface layer were lower in the Chinese rice cultivars than the Japanese rice cultivars, although the stickiness of the overall layer (‐H2) was higher in the Chinese rice cultivars than the Japanese rice cultivars. In addition, the texture of cooked rice was strongly correlated with the iodine absorption factors.
\nIn a previous study, we developed a novel formula for estimating AAC based on the iodine absorption curve. The validation test showed a determination coefficient of 0.996 for estimating AAC of Chinese rice cultivars as unknown samples.
As described in Section 3, in the case of physicochemical evaluation, we can get the common results for the rice samples produced in the different regions if we use the same method. As an example, we report the results of physicochemical measurements of rice palatability using rice samples produced by the different cultivation conditions, and rice samples grown in the mountainous region and the field region in Sado Island, Japan.
\nRice is one of the most important staple foods in the world. “Koshihikari” is the most famous premium rice cultivar, and it shares about 37% of all rice production in Japan. “Koshihikari” is cultivated all over Japan, but that grown in Niigata Prefecture is considered the best “Koshihikari” in Japan with regards to its quality and quantity. Sado Island is part of the Niigata Prefecture and the “Koshihikari” cultivated in Sado, Iwafune, and Uonuma is evaluated as the highest quality rice.
\nSado Island is located off the Niigata City seashore and it is the second largest island in Japan after Okinawa Island. Sado Island is famous for its Toki (crested ibis,
Sado city awards the farmers a harmonizing environment certificate known as the “homeland to live with crested ibis” if the farmers adopt an ibis‐friendly agricultural method. Farmers create a narrow pond, preserve bio‐diversity with winter‐flooding, and reduce the use of chemical fertilizers and agricultural chemicals by over 50% compared with conventional cultivation.
\nHowever, the effects of this ibis‐friendly agricultural method, which also include abolishing drying paddy field after transplanting, does not equate to palatability of the rice grains. Therefore, the relationship between the palatability of rice and agronomical condition to preserve the bio‐diversity for ibis was investigated. Furthermore, the quality of rice grown in Sado Island was compared with that of rice grown in mountainous areas and in the field.
Ten premium rice cultivars, including “Koshihikari” from Sado Island, “Sagabiyori,” “Yumepirika,” “Akitakomachi,” “Tsuyahime,”“Hitomebore,” and “Koshihikari from Sado” were subjected to physicochemical measurements and sensory test.
Rice samples grown in eight regions, including the mountainous and field regions, were subjected to the physicochemical measurements to evaluate rice quality.
Rice grains were harvested after an ordinary or ibis‐friendly cultivation and were subjected to quality evaluations. Ibis‐friendly cultivation meant that farmers adopted winter‐flooding (keeping water even during the winter season to save the habitat for Toki in winter) or deletion of “Nakaboshi” (drainage of paddy field for approximately a week after transplanting to activate the roots of rice plant).
After de‐husking, brown rice was polished to a milling yield of 90–91%, using an experimental TM05 rice milling machine (Satake, Co. Ltd. Higashihiroshima, Japan). Rice flours were prepared by a cyclone mill (SFC‐S1, Udy, Fort Colins, CO, USA).
Amylose content was measured by the iodine colorimetric method. Calibration samples were prepared by mixing the standard potato amylose (Type III, Sigma Chemical Co., St. Louis, MO, USA) and standard amylopectin (waxy rice removed from fat and proteins).
Protein contents and quality scores were measured with a near‐infrared spectrometer (AN820, Kett Electric Laboratory Co. Ltd., Tokyo, Japan) (Near Infrared Spectrometer, Foss Japan Co. Ltd, Tokyo, Japan). Mido was measured using a Midometer (Toyorice, Wakayama, Japan).
Polished rice grains (10 g) were added with 16 mL of distilled water in an aluminum cup. The rice was in the water for 1 h, cooked for 25 min in the automatic electric rice cooker (SR‐SW182, Panasonic Co. Ltd., Kadoma, Japan) and kept warm for 10 min in it. After the rice was kept warm, the boiled rice grains were moved into a plastic bag and kept in the bag for 2 h at 25°C. Thereafter, the physical property (hardness and stickiness) of each boiled rice grain (20 samples) was measured by a Tensipresser (My Boy System, Taketomodenki Co. Ltd., Tokyo, Japan), as reported by Okadome et al. (single grain low‐compression high‐compression test).
“Koshihikari” from the Sado Island received extremely high value for the quality value, Mido value, and low value for protein. “Koshihikari” from Sado Island had an extremely low hardness in surface layer of boiled grains, whereas extremely low amylose rice such as “Yumepirika” had the lowest hardness in surface layer of boiled rice gains. The ratio of stickiness to hardness of surface layer of boiled grains was the highest for “Yumepirika” followed by “Koshihikari” from Sado Island. Palatability of the “Koshihikari” from Sado Island seems to be one of the best premium rice cultivars in Japan due to its low protein content.
As a result of measurement of physical properties, five rice samples from mountainous regions showed a lower pasting temperature and a higher ratio of adhesiveness to hardness (A6/A4, overall). It was reported that the ratio of adhesiveness to hardness is correlated with palatability of boiled rice grains. Rice samples grown in the mountainous region seems to be more palatable than those in the field region because the former rice is more adhesive.
Rice samples grown using winter‐flooding (without “Nakaboshi”) showed higher amylose contents, than those grown with winter‐flooding and “Nakaboshi.” Rice grains grown using winter‐flooding and Nakaboshi had lower amylose contents implying that the boiled rice grains of this group were softer and stickier than the rice grains subjected to winter‐flooding alone. In case of cultivation using winter‐flooding, the rice grains grown using “Nakaboshi” became stickier after boiling compared with those cultivated without “Nakaboshi.” In case of cultivation without Nakaboshi, rice samples grown using winter‐flooding became less adhesive after boiling compared with those grown without winter‐flooding. These results are shown in Figure 7.
The effect of winter‐flooding and Nakaboshi on amylose contents of rice grains.
To summarize, farmers should adopt Nakaboshi in case of winter‐flooding, and avoid winter‐flooding in case of not performing Nakaboshi. Although adoption of winter‐flooding and not performing Nakaboshi are recommended to maintain biodiversity, simultaneously performing of both of these measures negatively affects the palatability of the boiled rice grains.
Farmers in Sado city make an effort to harmonize the environment with sound agriculture to protect the ibis from extinction. The palatability of “Koshhikari” from Sado Island is among the premium rice cultivars in Japan. The rice quality from Sado Island grown in mountainous areas and those in field regions were examined along with the palatability of rice and the agronomical conditions to preserve the bio‐diversity for the ibis.
\nThe results show that the palatability of “Koshihikari” from Sado Island seems to be one of the best among the premium rice cultivars in Japan because of its low protein contents. Five rice samples from mountainous regions showed better physical properties compared with three rice samples grown in the fields. Adoption of both winter‐flooding and not performing Nakaboshi is recommended to maintain biodiversity; however, simultaneously performing both of these measures negatively affects the palatability of the boiled rice grains.
There are various kinds of rice cultivars of which qualities are diversified, such as hard Indica rice and soft Japonica rice in the world. Consumers in southern Asia prefer hard rice grains and people in North‐eastern Asia like soft and sticky rice grains. Novel method to evaluate the quality of the cooked rice is necessary to breed high‐quality rice cultivars and to select the suitable rice for each consumer and for each purpose. We try to develop the novel method to evaluate the rice quality using various kinds of apparatus, such as Tensipresser, RVA, NIR, and spectrophotometer. Simple, rapid, and accurate method to evaluate the quality of rice grains is very valuable.
Cancer is a collection of diseases triggered due to uncontrolled cell division [1]. Cancer cells are able to migrate from their original site to any other site through the vasculature is what that makes them harmful [2]. Cancer occupies the second position in list of deaths worldwide by causing 9.6 million deaths in 2018. Cancer causes a tremendous economic burden on the patient and ultimately on the nation [3]. Traditional treatments for cancer include surgery, chemotherapy and radiation therapy [4]. The traditional therapies are now more advanced as the time has progressed. Yet, they have many drawbacks which make them ineffective for destruction of tumor [5]. Surgical treatments suffer from disadvantages such as early diagnosis, presence of micro metastases, disruptions of tumors and side effects of anesthesia [6]. Radiotherapy involves treatment with ionizing radiations with a drawback of non-discriminate action against healthy cells at the sites where cells have a rapid growth rate such as hair follicles. It causes side effects like hair loss, anemia, sores in mouth and throat, neuropathy, skin dryness, and change in skin color [7]. To prevent these side effects, nanoparticles are used that can penetrate inside the tumor due to their nanosize. It reduces not only the amount of drug used but also the associated side effects due to action at places where it is not needed [8]. Many nano-formulations such as nanosponges and nanoparticles have been invented for their delivery to cancer [9]. In this chapter, we have discussed about nanosponges, their classification, advantages, disadvantages, and how they are better than other nanocarriers. We have also enlisted the barriers affecting delivery to cancer and how nanosponges can be used to overcome them along with some applications of nanosponges along with functionalization of nanosponges to ease delivery to cancer. We have also discussed about toxicity of nanosponges and the probable mechanisms to reduce that toxicity.
Nanoparticles are nanosized particles containing polymers or lipids which contain drugs adsorbed or encapsulated in them [10]. One advantage of nanotechnology in cancer treatment is modifications of delivery system to achieve targeting [11]. Nanoparticle-mediated delivery of any cytotoxic agent allows control on the biodistribution of drug, hence controlling the toxicity [12]. Nanoparticles allow drugs with lower molecular weight to stay in the circulation for a prolonged period [13]. Nanoparticles being 1000 times smaller than a cancer cell can easily cross the vasculature and reach the interstitium. Due to their small size, and a relatively large surface area allows loading with large number of molecules [14]. Nanoparticles also help to remove difficulties due to innate properties of active pharmaceutical ingredient (API) such as poor solubility can be overcome by using water-soluble polymers to trap the drug within [15]. Many chemotherapeutic agents which have low molecular weight face issue of hepatic clearance, but conversion into nanoparticles prevents quick clearance [16]. Nanoparticles reduce the exposure of drugs to the environment inside the body and prevent the degradation of the drugs and the side effects due to exposure of healthy cells to cytotoxic drugs [17]. Nanoparticles are being explored to give multiple actions at the same time. The researchers Xie et al. [18] inserted curcumin into nanoparticles made from bamboo charcoal. The nanoparticles were functionalized using D-α-tocopherol polyethylene glycol 1000 succinate. Due to a nano-formulation, the system gave better internalization, and this composite dosage form showed inhibition of P-gp which increased the efficacy of treatment. At the same time, the presence of antioxidants such as tocopherol and curcumin helped to remove any reactive radicals and showed radioprotective action [18]. Ma et al. [19] synthesized nanoparticles of poly-(acrylic acid) with CoSe using the aqueous precipitation method. These particles had photothermal transfer efficiency greater than 40% and negligible cytotoxicity. These nanoparticles were loaded with doxorubicin (DOX) which was shown to release in the acidic tumor conditions in cancer. These particles gave a synergistic cytotoxic action due to chemotoxicity as well as phototoxicity [19].
Hu et al. [20] synthesized gold nanoparticles by rapidly reducing gold chloride trihydrate. To that solution, thio-PEG and thio-glucose were added which showed covalent bonding on gold nanoparticles. Glucose was attached to take advantage of excess glucose consumption of cancer cells as compared to normal body cells. The cells were allowed to take in the Glu-GNPs which were found to be effective than only irradiation or only gold nanoparticles [20].
Tumors are a major presentation in cancer which exhibit presence of abnormal cellular and extracellular elements which can create obstacles in drug delivery to cancer cells situated deep within the tumors. Below given are barriers to drug delivery in tumors and ways to overcome those barriers-.
Biological barriers include physiological components which prevent the reach of drug to tumors. To reach the desired site, the drug should circulate in the blood. Blood contains many proteins that form a structure around the drug particle called ‘protein corona’. This phenomenon is called opsonization, and such opsonized particle is destroyed by phagocytes and macrophages. The physical characters of nanoparticle are determinants of extent of opsonization [21]. To prevent opsonization, the circulatory time is controlled using polymers such as PEG [22]. Yapa et al. targeted leucocytes and neural stem cells to facilitate entry into tumors as well as targeting metastases. The nanosponges were formulated using cholesterol and a CASPASE-6 sequence ((cholesterol-(K/D)nDEVDGC)3-trimaleimide) attached to a triangular maleimide linker which were then used to join lysine or aspartic acid. These function as apoptotic bodies and destroy the tumors [23]. If the nanoparticle avoids being opsonized, it still has to face many challenges to reach to its target sites, one being endothelium of blood vessels which is selectively permeable and on the top of that, being ‘coated’ by a negatively charged glycocalyx, it further restricts the reaction of particles with endothelial membrane [24]. Haemodynamic involves movement of nanoparticles through the blood vessels. As erythrocytes flow in the centre of the vessel, the other contents of blood are forced to move along the walls of the vessel. Understanding this phenomenon in context of nanoparticles will be helpful in design of better nanoparticles [25]. Particles larger than 5–6 nm are not able to squeeze through the continuous endothelium of a ‘healthy’ capillary. But in case of tumors, endothelial lining is more permeable and does not remain continuous. So, nanoparticles larger than 6 nm can cross these gaps to enter into the tumor microenvironment [26]. Because of inadequate lymphatic drainage, those particles do not get removed from the body. There is also a disparity in the sizes of the pores, which can be found in primary tumors, metastasized tumors, and even the same primary tumor, which is another drawback of this the enhanced permeability and retention effect (EPR) effect [27].
After the nanoparticle crosses successfully the endothelium and enters the tumor, it still has to cross the tortuous tumor microenvironment to reach to the tumor cells. The microenvironment consists of the tumor extracellular matrix that contains a network of collagen, elastin incorporating proteoglycans and hyaluronic acid. It maintains the tumor structure and provides nutrients and oxygen to cells. If the matrix is highly developed, it may cause the drug to get released far away from the target site [28]. Incorporating collagenase in the nanoparticles may help circumvent the collagen barrier and allow reach of nanoparticles [29]. The tumor growth cannot be infinite and is arrested because of presence of an extracellular matrix. The extracellular matrix also prevents efficient metastasis of the tumor cells. Tumor cells release various enzymes to degrade this matrix which are called matrix metalloproteinases [30]. These can be used in diagnosis of cancer as a marker. In this enzyme family, types 2 and 9 are more important in formation of tumors. Using drugs which inhibit metalloproteinases can be a best possible approach to counter this resistance [31]. Wang et al. synthesized nanosponges loaded with matrix metalloproteinase-14 inhibitor naphthofluorescein, which targets collagen in cardiovascular disease [32]. Flow of interstitial fluid in the tumor affects drug distribution as the drug exits vasculature from interstitium and finally reaches to cells. The movement occurs either by a concentration or a pressure gradient. As the blood vessel network is not uniform within a tumor, so the blood flow becomes uneven. Also, the drainage of interstitial fluid is poor due to poorly formed lymphatic network. It increases the interstitial fluid pressure. Due to high heterogeneity in tumor structure, the fluid pressure can be different for two tumors in the same organism [33]. As cancer cells prefer a type of fermentation over aerobic respiration, the amount of oxygen decreases and the number of acids increases near the centre. These conditions make the tumor resistant to certain treatments as radiation [34]. Hypoxia causes increased production of chemokines which promote angiogenesis and avoids detection from immune cells [35]. Also, the acidic pH may aid in targeting by using acid-sensitive polymers to release medication at the centre of tumor [36]. Caldera et al. synthesized nanosponges from cyclic nigerosyl-1-6 nigerose using pyromellitic dianhydride as a crosslinker. The nanosponges were prepared using high-pressure homogenization and showed swelling at lower pH which caused DOX release [37].
Cellular barriers include various cellular components which prevent the reach of the drug to intracellular environment. Many drugs show their effects inside the cell. Hence, even if the drug reaches near cancer cells inside the tumor, it has to cross the cell membrane to enter inside the cell to exert its actions. The carrier should interact with cell membrane to achieve the release [38]. Physical characteristics of carrier such as size, surface charge and hydrophobicity affect the interaction with cell membrane. Charged particles show more interaction with cell membrane. Neutral particles may crowd near cell membrane preventing any further entry into the cell [39]. Particles smaller than 200 nm get internalized by clathrin-mediated endocytosis, and those which are larger undergo clavioline-mediated endocytosis. This process is an energy-dependent process. Cancer cell membranes express many ligands which can be targeted [40]. Singh et al. [41] prepared cyclodextrin nanosponges and attached cholesterol as a functionalization moiety. Cholesterol being a major component of cell membrane facilitates easy interactions with cell membrane and hence easy penetration in cells.
Once inside the cell, the carrier should travel to the designated target site so as to release the drug. This travel is mediated by endosomes, which is energy-dependent. Endocytosis occurs by various pathways physiologically, and the pathways may be different for different types of nanoparticles. Generally, all these pathways end up in taking contents to lysosomes where they are destroyed. Use of fusogenic lipids is advised to prevent this fate [42]. Yan et al. synthesized nanosponges and coated them with fusogenic lipids which enhanced internalization and a better delivery inside the cells [43].
Till the medications reach the target site, only a small fraction of original dose remains which shows its effect. Hence, many tumors contain efflux pumps which remove the drugs out of tumor cells [44]. P-glycoprotein is one such receptor to throw the drugs out of cells. Various small molecules which are P-glycoprotein inhibitors can be used to avoid the efflux [45]. Arima et al. [46] prepared nanosponges of dimethyl-β-cyclodextrin and loaded them with an immunosuppressant tacrolimus. These complexes were tested on rats where they showed increased bioavailability and dissolution rate. Pre-treatment of apical membrane with dimethyl-β-cyclodextrin showed dislodging of receptors from the membrane and successfully inhibited P-glycoprotein showing increased absorption of drugs [46].
Nanosponges are sponges of very small size with diameter less than 1 μm. These are three-dimensional networks made of polymers which act as frames to hold the drug molecules inside them. These sponges circulate the body and can release the drug at a specific site [47].
Nanosponges offer advantages over other nanoparticles such as a targeted release of active constituents inside the body which is caused due to functionalization on the surface. Nanosponges allow flexibility of formulation due to various polymers used as well as stability due to the drug entering the pores of sponge. These are non-toxic, non-allergenic and non-mutagenic due to biocompatible ingredients used. As these sponges are made of biodegradable molecules, they are able to provide extended release due to slow degradation of drug. Nanosponges are stable over wide temperature range and show excellent stability over the pH range. As nanosponges have diameter less than a bacterium, the formulation is self-sterile as bacteria are unable to enter the formulation. They exhibit excellent thermal, physical and chemical stability [48].
Nanosponges can be used for only small molecules as large molecules may not enter the nanosized pores of nanosponge. The drug loading is also affected by the degree of crystallization. Dose dumping may be observed due to sudden degradation of carrier [49].
The classification of nanosponges based on the material used is illustrated in Figure 1A [50].
(A) Classification of nanosponge—this figure shows classification of nanosponges based on the materials used for synthesis. (B) Beta-cyclodextrin nanosponge—beta-cyclodextrin nanosponges are prepared by crosslinking beta-cyclodextrin molecules using crosslinkers. (C) Metal nanosponge—these are made by irregular arrangements of metal nanoparticles in irregular ways to create pores and channels on the surface. (D) Polystyrene nanosponge—the polystyrene is chloromethylated and reacted with tin chloride to give a hyper-condensed polymeric nanosponge.
Cyclodextrins have been majorly used for the preparation of nanosponges. These are cyclic oligosaccharides. These are cone-shaped molecules made of glucopyranose units. These units are arranged around a hydrophobic hollow core which is used to trap any molecules.
Selection of crosslinkers is important to alter the properties of the final product. Crosslinkers such as epichlorohydrin give cyclodextrin nanosponges with hydrophilic pores whereas crosslinkers such as diphenyl carbonate and diisocyanates give hydrophobic nanosponges [51]. Various types of cyclodextrin-based nanosponges are enlisted in Table 1 and Figure 1B [52].
Type | Crosslinker used | Example | Method used |
---|---|---|---|
Cyclodextrin carbonate nanosponges | Carbonyl crosslinkers | Diphenyl carbonate Dimethyl carbonate | Thermal deposition Solvent extraction |
Cyclodextrin carbamate nanosponges | Diisocyanate crosslinkers | Hexamethylene diisocyanate Toluene diisocyanate | Solvent method |
Cyclodextrin anhydride nanosponges | Anhydride crosslinkers | Pyromellitic dianhydride EDTA dianhydride | Solvent method |
Epichlorohydrin cyclodextrin nanosponges | Epichlorohydrin crosslinkers | Epichlorohydrin | Solvent method |
Different types of beta-cyclodextrin-based nanosponges.
Metal and metal oxide nanosponges have desirable characters such as a wide surface area, small particle size and better stability. Metal oxides are being shown interest due to their ability of interaction with other species such as atoms, ions and molecules. They are able to form a porous interconnected network and show properties different than bulk. These also show magnetism and semiconductor properties. Metallic nanosponges can be made from one, two or multiple metals simultaneously. The nanosponges made from two or more metals are desirable over those made from single metal as they are more porous and based on porosity, and they can be classified as micro, meso and microporous based on the size of sponge where microporous are smaller than 2 nm, macroporous being larger than 50 nm and mesoporous lying in between them (Figure 1C) [53].
Davankov et al. [54] prepared nanosponges of linear polystyrene by causing intramolecular hyper-crosslinking. The polymer was initially chloromethylated using dichloro monoethyl ether, and this solution was added to the solution of zinc chloride in the same ether which acted as a catalyst. This mixture was heated at 40°C for 3 h. The precipitated polymer was washed and dried. This polymer is dissolved in 2 L ethylene dichloride distilled over phosphorous pentoxide. Tin chloride solution was added which changed the colors gradually from pink to brown. Acetone was added to dissolve colored complex. The solution was allowed to cool and was washed with water. The organic layer was separated and concentrated to 20% of starting volume. The nanosponges were isolated using methanol. They were dried and stored (Figure 1D) [54].
For the formation of nanosponges made out of polymer, reaction conditions such as heat and solvents promote uncoiling of long polymer chains and reveal the groups for reaction with crosslinkers. Crosslinkers such as diphenyl carbonate release the phenyl group upon reaction which remains in reaction mixture, and the carbonyl group acts as crosslinkers during the formation of nanosponges. The extensive crosslinking causes winding and coiling of long polymer chains and forms pores and cavities leading to the formation of nanosponges. The prepared formulation is later purified using organic solvents such as ethanol to remove those impurities.
Cyclodextrins are made to react with crosslinkers like diphenyl carbonate, dimethyl carbonate and diisocyanates. All the dry ingredients are homogenously mixed and put into a flask and heated at 100°C. A magnetic stirrer is used to achieve uniform mixing of contents. The heating is kept up for a total of 5 h so that the reaction can take place. After allowing the mixture to cool down, the obtained solid is broken up into smaller pieces using mortar. It is then purified using the Soxhlet extraction method after being washed to remove any unreacted reactants [55]. Sadjadi et al. synthesized beta-cyclodextrin nanosponges using the melt method. A calculated amount of diphenyl carbonate was melted at 90°C in a beaker. Preheated beta-cyclodextrin was added to it. The mixture was stirred for half a day at temperature exceeding 100°C to allow reaction to get completed. The solidified product was cooled and pulverized. The product was washed using water and organic solvent and later purified using Soxhlet extraction [56].
Ethyl cellulose and polyvinyl alcohol are used to prepare nanosponges. Cellulose and drug are dissolved in organic solvent such as dichloromethane. Then this dispersed phase is added to continuous phase which is aqueous poly (vinyl) alcohol (PVA) solution. This mixture is stirred at high speed for a specific amount of time, and the product is filtered and dried [57]. Solunke et al. [58] prepared gliclazide nanosponges using emulsion solvent diffusion method. Gliclazide and Eudragit were added to organic phase, and aqueous phase was a PVA solution. Organic phase was added to aqueous phase, it was stirred, and nanosponges were collected and washed [58].
This process involves polymers such as Eudragit. The polymer is dissolved into a solvent and the drug is added to same solution. This inner phase is added to PVA solution and stirred. The product is filtered out and dried [59]. Salunke et al. [60] prepared budesonide-loaded nanosponges by quasi-emulsion solvent diffusion method. Weighed amounts of Polymethyl-methacrylate (PMMA) and Eudragit S-100 were dissolved in organic solvent containing dichloromethane and methanol in equal proportions. Dibutyl phthalate was added to enhance polymer plasticity. The organic phase was added to aqueous PVA solution and was stirred for 2 h. The prepared nanosponges were recovered by filtration and were washed and dried [60].
The polymer is mixed with an aprotic solvent such as dimethyl sulfoxide. Carbonyl crosslinkers are added to this solution. The reaction is allowed to take place at a range of temperature which may not increase the boiling point of solvent. The solution is cooled at room temperature, and a large amount of water is added to it. The product is recovered by filtration [61]. Rao et al. [62] synthesized nanosponges by the solvent method by dissolving anhydrous β-cyclodextrin and diphenyl carbonate and heating that solution at 90–100°C under stirring. The prepared product was washed with water and later with organic solvents to remove any unreacted constituents. The product was dried to use later [62].
This method involves energy from ultrasound to carry on the reaction. The reactants are placed in the flask and heated with help of ultrasound. The mixture is allowed to react. Later the product is cooled down and broken with mortar. The product is washed with water and purified by Soxhlet apparatus [63]. Jasim et al. [63] prepared cyclodextrin nanosponges using ultrasound-assisted method. Weighed quantities of β-CD and diphenyl carbonate. The mixture was heated on an oil bath and was sonicated using a probe sonicator at 50% amplitude for 4 h. The product was broken down and washed to give final product [63].
Metal nanosponges are prepared by reducing a metal salt using a suitable reagent. Surfactants or capping agents are used to control the growth rate and structure of nanosponges. Ghosh and Jagirdar [64] prepared silver nanosponges in their research activity. Silver nitrate was used as a substrate for synthesis on nanosponge. The salt was reduced to silver cations using boranes. This reaction was carried out at a temperature above 300 K. The reduced metal salt releases free metal atoms. These join together to form nanoparticles. These nanoparticles join together to form nanosponges due to their irregular joining which produce pores or gaps in the structure. This process works like bottom-up approach of synthesis of nanoparticles as they are built from the atoms themselves [64]. Different mechanisms are used to prepare metal oxide nanosponges such as precipitation and removal from alloy. Dealloying involves removal of a more reactive metal from an alloy. Chemical dealloying is the most common method involving use of acids to react with more reactive metal to remove it from the alloy. Alloy nature and leaching conditions affect this process. Another method utilizes the mechanism of precipitation of metal separated from its salt. This separation is brought about by using reducing agents such as NaBH4. Later, it is heated at very high temperature to deposit the metal oxide which gives out hydrogen bubbles which are responsible for generation of channels and pores which are required for drug loading. A disadvantage is the variable pore size due to uncontrolled particle size which gets sedimented. Electrochemical deposition utilizes the mechanism of movement of ions towards the oppositely charged electrodes. The ions that migrate form a thin film on the surface of metallic/metal electrode. The changes in pH, temperature and current density can be carried out to vary the properties of the sponge prepared. Another method based on hydrolysis of metal precursors and their conversion to metal species is the sol-gel method. It involves electrolysis of metal compounds in ‘sol’ phase in a solvent. After passing the electric current, the metal particles deposit on the electrode with internal pores and cavities in form of gel. The coagulation of prepared particles can be avoided by altering pH of medium. Drying is performed by evaporation or supercritical methods which evaporate the solvent and forms pores [53].
Nanoparticles after reaching the site of action release their loaded drug all at once creating a ‘burst’. Hence, effective dosage cannot be determined properly, whereas nanoparticles being made of biodegradable polymers release their drugs in a slow, controlled manner after the sponges encounter a tumor [48]. Nanosponges are soluble in aqueous as well as organic solvents. These are non-toxic carriers which are heat-stable [65]. Nanosponges are water-soluble which allow the researchers to use them for dissolution of insoluble drugs after loading them into the sponge [66]. Loading and functionalization of nanosponges is pretty easy as compared to other nanoparticles. The functional groups protruding out of nanosponge surface can be used for post-modification strategies such as functionalization [67]. Many nanoparticles have complex chemistry; hence, they cannot be scaled up easily for large-scale production. On the other hand, nanosponges made of only polymers and crosslinkers are easy to scale up for commercial production [68]. As compared to other nanoparticles, where reconstruction of nanoparticles is difficult if they lose their structure, nanosponges can be easily remade by methods such as washing with eco-compatible solvents, mild heating or changing pH or ionic strength [69]. Where many types of nanoparticles are used to contain solid medications, nanosponges can be used to encapsulate not only solids but also liquids and gaseous drugs [70]. Nanosponges can be used to load both hydrophilic and hydrophobic drugs owing to the hydrophobic core and external hydrophilic branching. Hence, these nanostructures can be flexibly loaded with hydrophilic or hydrophobic molecules [71]. Figure 2 highlights major researches on nanosponges from 2005 to 2022.
Nanosponges major research timeline.
Nanosponges can be prepared with a variety of methods and then can be loaded to give a varying amount of drug loading. Kumar et al. [72] prepared cyclodextrin nanosponges loaded with babchi oil using tiring at high speed. Similar approaches are described in Table 2.
Polymer | Drug | Loading method | Loading efficiency | Reference |
---|---|---|---|---|
Β-Cyclodextrin | Babchi oil | Blank NS were dispersed in water. Excess amount of babchi oil was added and stirred for 24 h. The suspension was centrifuged. The supernatant was freeze-dried | 21.47% w/w maximum and 14.23% minimum | [72] |
β-Cyclodextrin | Griseofulvin | Drug dispersed in aqueous colloidal dispersion of NS having PVP. Suspension was stirred and centrifuged. Supernatant was freeze-dried | Maximum 47.2% and minimum 20.20%, based on formation of ternary complex | [73] |
β-Cyclodextrin | Celecoxib | Method 1: Drug and polymer were dissolved in dimethyl formamide. This solution was stirred. Crosslinker was added to same solution. (internal phase) This was added to water (external phase) and stirred. The suspension was lyophilized | After using N,N-methylene bisacrylamide, 22.11 ± 0.41 to 26.26 ± 0.24%. Loading was seen. | [74] |
Method 2: Drug and polymer were dissolved in dimethyl formamide. (internal phase) This was added to crosslinker in water (external phase) and stirred. The dispersion was lyophilized | After using glyoxal, 22.48 ± 0.23 to 24.85 ± 0.47% loading was achieved | |||
Β-Cyclodextrin | Piperine | NS were suspended in water and stirred. Then the drug is gradually added. The dispersion was sonicated and then stirred. The suspension was centrifuged to remove excess of drug. The supernatant was lyophilized and stored in a desiccator. | Loading efficiency was 42.6 ± 1.1% | [75] |
Β-Cyclodextrin in Fe3O4 nanoparticles coated by β-CD NS | Curcumin | Nanoparticles were dispersed in PBS. Curcumin solution in acetone was added to the suspension. Mixture was shaken overnight in dark. The product was separated using a magnet and washed by de-ionized water | Loading efficiency was 96% at 1:2 ratio of drug: carrier | [76] |
Β-Cyclodextrin | Camptothecin | Drug was added to aqueous nanosponge suspension and stirred for 24 h in dark. The suspension was centrifuged to separate free drug. Colloidal supernatant was freeze-dried | Loading efficiency was 38% w/w | [77] |
Β-Cyclodextrin | Curcumin | Curcumin dissolved in dichloromethane. Nanosponges were added to this solution and triturated till solvent evaporates. The product was dried | 46.45 ± 0.54 mg and 48.37 ± 0.47 mg of curcumin/100 mg of F1 and F2 respectively | [78] |
Β-Cyclodextrin | Nifedipine | Prepared nanosponges and nifedipine in excess were mixed and were suspended in distilled water. The mixture was sonicated and then stirred. Aq. Suspension centrifuged to separate free drug. Supernatant was lyophilized | Encapsulation efficiency was 78.4 ± 0.24% | [79] |
Ethyl cellulose | Lansoprazole | Drug and polymer were added to dichloromethane. This disperse phase was added to aq. PVA solution. Mixture stirred for 2 h. Prepared NS were filtered and dried | Entrapment efficiency was 86.93 ± 0.65% in F2 | [80] |
Methods of preparation of nanosponges.
Optimization involves obtaining a best combination of starting materials to get a formula which gives the desired results. Due to a simple composition, nanosponges can be optimized without much hassle, which is evident from the examples given in Table 3.
Sr. no. | Model used | Dependent var. | Results | Reference |
---|---|---|---|---|
1 | Box-Behnken | Polymer conc (mol) Crosslinker conc (mol) Reaction time Particle size Entrapment efficiency | Particle size depends directly on polymer concentration | [81] |
2 | 32 full factorial design | Amt of β-CD (gm) Amt of DPC (gm) Porosity Zeta potential Drug loading Drug release | As B-CD conc increase and porosity increases. Zeta potential depends on particle size only. Drug loading depends upon DPC conc. | [82] |
3 | 32 full factorial design | THCL:EC ratio (w/w) Stirring rate (rpm) Particle size Production yield (%) Entrapment efficiency | Particle size reduced as stirring rate increased. Entrapment efficiency decreased by increasing stirring rate. Production yield increases as polymer conc increases. | [83] |
4 | Robust model | Amount of EC Amount of PVA Particle size Entrapment efficiency | Particle size increases with increase in drug-polymer ratio. | [84] |
5 | 23 full factorial design | Amount of HP-β Amount of β-CD Amount of CDI % Entrapment efficiency Particle size | Particle size decreases with increase in concentration of CDI and β-CD. % Entrapment efficiency increases with increase in concentration of HPβ-CD and β-CD. | [85] |
Optimization of nanosponges.
Morphological characterization involves various instrumental methods to analyze the morphology of prepared nanostructure. Transmission electron microscopy (TEM) involves scanning a sample with a beam of focused electrons which is transmitted through the sample to understand composition of particle. Argenziano et al. [86] prepared β-cyclodextrin nanosponges loaded with paclitaxel. Pyromellitic anhydride was used as a crosslinking agent. Methods such as high-pressure homogenization were used to reduce the particle size. The analysis was performed on Philips CM 10 device. The sample was prepared on formvar-coated copper. The coated samples were air-dried. The results showed that spherical particles were formed. The size was in nano-range due to application of high-pressure homogenization in the synthesis of nanosponges [86]. Scanning electron microscopy involves scanning a sample using an electron beam focused on sample which is then converted into signals. Mady and Mohamed Ibrahim (2018) prepared nanosponges using β-cyclodextrin and diphenyl carbonate crosslinker in DMF as solvent. The mixture was sonicated and refluxed using water and ethanol to remove impurities. Scanning electron microscopy was carried out using model LEO-435 VP, Cambridge (UK). It was used at 15 KV accelerating voltage, and different resolutions were used to obtain images. The images showed a perfect spherical shape of loaded nanosponges. Some drug particles were present on the surface as well as numerous porous channels were present on the surface. As compared to blank nanosponges, drug-loaded nanosponges were more porous [87]. Atomic force microscopy involves interactions of probe with sample through up-down and side-to-side movement along area of sample which is checked using a laser beam. Choudhary et al. [88] synthesized two peptides. And these linked peptides were attached to a trimaleimide frame. It gave two structures with positive and negative charge. Then using those differently charged structures, two variants were formed having 15 and 20 subunits, respectively. These two types of structures were mixed under conditions mimicking human body which resulted in the formation of nanosponges. 0.05 M stock solution of NS was prepared in PBS, and a drop was added on a freshly prepared mica sheet. The buffer was removed using nitrogen stream for 2 min. Bruker Innova AFM system was used to take the pictures using a TESPA-HAR probe in tapping mode. Spring constant was kept 50 N/m and operated at a frequency of 350 KHz. Images were taken at a scan rate of 1 Hz. The structures with 15 subunits showed formation of bundles made from three to five subunits. The structure with 20 subunits formed excellent nanosponges in the range of 80–115 nm [88]. Photon correlation spectroscopy involves measuring Brownian motion of particles as a function of time which is recorded by scattering of laser where scattering is directly proportional to particle size. Yakavets et al. [89] synthesized nanosponges from ethyl cellulose, PVA and pleuronic F68 by emulsion solvent diffusion technique. The particle size was measured using a Nano ZS-90 (Malvern instruments Ltd., UK) at an angle of 25°. The sample was diluted 10 times and analyzed. The composition F2 showed minimum particle size at 83 nm [89]. Wang and Schaaf [90] synthesized size-controlled Au-Ag nanosponges. Their structural characterization was carried out using SEM and TEM. Advanced techniques, such as focused ion beam, were used to reveal the hybrid composition of nanosponges. 3D structural properties were analyzed using techniques such as synchrotron X-ray nanometography. Atom probe tomography can be used where the obtained images are aligned again and again to allow reconstruction of particle image and thus to obtain the parameters. Nanosponges have peculiar optical properties due to their complex structure. Properties such as optical scattering and photoluminescence can be measured using dark field florescence confocal microscopy [90]. The analytical techniques may vary with use of the final product. Maity et al. [91] synthesized nanosponges of acidic aminosilicates for the purpose of catalysis. Those were analyzed using morphological characterization techniques such as SEM and TEM which confirmed the formation of nanosponges as well as their porous structure. X-ray diffraction studies were carried out to understand the percentage of aluminium precursors. 1-D and 2-D NMR studies were carried out to understand the locations of catalytically active sites of nanosponges. A temperature-programmed desorption study using ammonia was carried out to understand the distribution of acidic sites in nanosponges and to identify their correlation with NMR data [91].
Encapsulation efficiency indicates the amount of drug which gets successfully entrapped in a nanoparticle. Rezaei et al. (2019) prepared cyclodextrin nanosponges loaded with ferulic acid where three ratios of β-CD: crosslinker taken namely 1:2, 1:4 and 1:8 were synthesized. To determine the encapsulation efficiency, drug-loaded and blank nanosponges were suspended in ethanol and sonicated at room temperature separately. The sonicated dispersions were filtered using a filter paper with pore size of 0.45 μm. Ferulic acid content was determined using UV-visible spectrophotometry at 319 nm. The analysis showed that nanosponge prepared with 1:4 ratio of β-CD to crosslinker showed maximum encapsulation as lower ratio resulted in an insufficient amount of crosslinking and a ratio of 1:8 showed hyper-crosslinking, hence reducing the amount of encapsulated ferulic acid [92]. Dhakar et al. [93] prepared cyclodextrin nanosponges loaded with resveratrol and oxyresveratrol. The prepared nanosponges were added to water to give a solution of 10 mg/ml, and drugs were added in different ratios of drug: nanosponge, i.e. 1:2, 1:4 and 1:6. The mixtures were stirred for a day in dark after sonicating them for some time. The supernatant was collected after centrifugation of formulation, and it was lyophilized to give a dry powder. The powder was subjected to High-performance liquid chromatography(HPLC) analysis to understand loading of the drugs. The powder was taken in vials containing ethanol and sonicated for an hour. It was analyzed using High-performance liquid chromatography(HPLC). The drug loading was maximum in the ratio of drug to nanosponge which is 1:4, since saturation solubility was achieved. The encapsulation efficiency of the nanosponges was found to be 77% for resveratrol and 80% for oxyresveratrol. In addition, the encapsulation demonstrated an increase in the solubility of previously insoluble compounds. Diphenyl carbonate and beta-cyclodextrin were used to make nanosponges in various molar ratios, including 1:2, 1:4, 1:6, 1:8, and 1:10. Through the process of freeze-drying, which involved adding specific amounts of blank nanoparticles and babchi oil to water, stirring, and sonicating for a day, they were loaded with the babchi oil. The mixture was centrifuged to remove the oil which did not enter the inclusion complex. The supernatant was removed and freeze-dried. A specific amount of NS were added to dimethyl sulfoxide and sonicated to separate drugs from complex. The samples were analyzed using UV spectrophotometer at 265 nm. The encapsulation efficiency was observed in the range 62–93%. The maximum efficiency was present in formulation with the molar ratio of cyclodextrin to carrier 1:4. In formulations with higher number of crosslinking agents, hyper-crosslinking resulted in less loading [72]. Appleton et al. [94] prepared β-cyclodextrin nanosponges by reacting polymer, triethanolamine and pyromellitic dianhydride in DMSO at 90° in an RBF. The prepared product was solidified, washed and ground. The coarse product was ground and purified with acetone using Soxhlet extraction. Insulin was loaded in blank carriers by mixing an acidic solution of drug in a solution of nano-formulation where the ratio between insulin and nanosponges was 1:5. The mixture was stirred, and the sediment was lyophilized. Such prepared nanosponges were added to a mobile phase in a proper concentration and sonicated. The solvent was analyzed using UV spectrophotometry. The encapsulation efficiency was 91% [94]. The product was washed using water and ethanol and later purified using Soxhlet extraction. For loading, solvents such as ethanol, methanol, acetone and only essential oil were tested for four different time intervals from 1 to 4 days. A weighed quantity of nanosponges were placed in a microtube, and coriander essential oil dissolved in a solvent was added. The mixture was stirred at room temperature to facilitate loading. Then the sample was centrifuged to separate the loaded nanosponges and was freeze-dried. After freeze-drying, the samples were dispersed in acetone and stirred for a day which were later centrifuged to separate the acetone supernatant. The obtained supernatants were analyzed using Gas chromatography–mass spectrometry (GC-MS). Five major constituents such as pinene, cynene, camphor, linalool and geranyl acetate were used to detect quantitatively [95].
Anticancer drugs are notoriously famous for their side effects which can be decreased by the use of nano-formulations which reduce the dose required and hence the side effects. Wang et al. synthesized nanosponges from DNAzyme-containing ZnO to release therapeutically active ROS [96]. Table 4 indicates such similar results and show enhanced action of dosage forms over administration of single API.
Drug | Polymer | Cancer type | Studies performed | Results | References |
---|---|---|---|---|---|
Doxorubicin | Β-cyclodextrin | Breast cancer | Human MDA-MB231 and MCF-7 cell lines, mouse 4T1 (DOX-sensitive) and EMT6/AR10r (DOX-resistant) cell lines, efficacy using MTT assay | Concentration-dependent inhibition of cell viability which was more than doxorubicin | [97] |
Erlotinib | Β-cyclodextrin conjugated with glutathione | Lung cancer | Human lung carcinoma cells (A549 cells), MTT assay to determine efficacy | Dose- and time-dependent inhibition of proliferation of A549 cells. Nanosponges showed better effect at lower dose than only erlotinib. | [98] |
Paclitaxel | Β-cyclodextrin | Melanoma | Types of human cell lines used—A375, M14, JR8, RPMI7932, PCF-2 and LM. Types of mice cell lines used—B16-BL6 | The formulation showed increased oral bioavailability and efficacy as compared to free drug. The formulation showed considerably lesser toxicity as compared to free drug. The formulation also showed inhibition of metastasis and growth. | [99] |
Ferulic acid | Β-cyclodextrin | Breast cancer | MCF7 cell lines for human breast cancer and 4T1 cell line for mouse breast cancer, using MTT assay | The cytotoxicity was observed at concentration above 500 սM. The cytotoxic effect was time-dependent. As the formulation enhanced the solubility, the inhibitory concentration was reduced. | [92] |
Strigolactone | B-cyclodextrin conjugated with glutathione | Prostate cancer | DU145 and PC-3 prostate cancer cells, efficiency studied using MTT assay | The free drug as well as nanosponges inhibited the cell proliferation. This activity on the formulation was dependent on intracellular GSH amount. | [100] |
Bortezomib | B-cyclodextrin | Breast cancer | MCF-7 cell lines for human breast cancer were used, and MTT assay for checking the proliferation | The complex showed high loading, sustained release, and aqueous dispersion. The cytotoxicity was found to be reduced due to sustained release effect | [101] |
Naphthofluorescein | Poly(VL-AVL-EVL) conjugated with T-Peptide_ACPP and cyanine-3 hydrazide | RAW cells and HT1080 cells were used; MTT assay used for testing efficacy | The formulation was able to locate collagen in presence of MMP2 enzyme. Both the types of cells showed a good extent of internalization. | [32] | |
Doxorubicin | Oligonucleotide DNA | MCF-7 cells and Hs 578 Bst cells were used for analysis, and MTT assay used for efficiency | The DNA nanosponges were broken down at acidic pH. These carriers were able to overcome barriers and target cells. The cytotoxicity was similar to free drug due to less release | [102] |
Nanosponges for delivery of anticancer drugs.
Functionalization involves attachment of various functional group or functional molecules on nanoparticle surface. Such a process imparts targeting properties to the nanoparticle. Femminò et al. functionalized cyclodextrin nanosponges using oxygen to relieve hypoxic conditions in ailments such as tumors [103]. Some examples of functionalization of nanosponges using chemical as well as biological functional ingredients are shown in Table 5.
Polymer | Functionalized by | Rationale | Reference |
---|---|---|---|
PLGA | Cancer cell membrane | By coating with cancer cell membrane, the particle shows homologous binding and bio-mimetic and targeting capacity. It possesses properties of a cancer cell to allow targeting. | [104] |
Carbon quantum dot-polyethylene glycol bisacrylate | Hydrazine | The carboxyl groups of Crosslinked carbon quantum dots (CQDs) were amidated using hydrazine to imine to give an acid labile bond which will be broken down in acidic tumor environment. | [105] |
Fe3O4 nanoparticles coated with B-CD nanosponge | Folic acid | Fe3O4 nanoparticles as a core to provide clear visualization during MRI. Folic acid for smart drug delivery and specific targeting. | [78] |
B-cyclodextrin | Cholesterol | Cholesterol is a major component of cell membrane. Attachment of cholesterol on surface of nanosponges allows bioadhesion and enhances cellular uptake. | [41] |
Gold nanosponge | Poly (N-isopropylacrylamide–methacrylic acid–1,4-dioxane, octadecyl acrylate) | pH- and thermal-responsive polymer. | [106] |
EpDT3 | An aptamer which binds to EpCAM, a biomarker present on cancer cell, helps on targeting. | ||
Reduced graphene oxide-lipid nanosponge | Protein Lf (Lactoferrin) | Lactoferrin shows selectivity towards cancer cell and inhibits cancer cell proliferation and migration. | [107] |
Functionalization of nanosponges.
Nanosponges have been limited for catalytic action or use as a carrier. Mostly simple nanosponges or those with basic functionalization are synthesized and used for delivery of single therapeutic agents, but the future trends are nanosponges that have been designed for storage of phase change materials. 3-D carbon-based materials such as nanosponges are preferred for loading of phase change materials which can be applied in locations such as operation tables, storage of medical and pharmaceutical products. Nanosponges can show advantages for application of both solid- and liquid-phase change materials. Carbon nanosponges have high loading and can be filled with a high number of materials. And nanosponges do not behave to changes in temperature [108, 109, 110]. Korea Ceramic Technology Institute developed a thermosponge for the treatment of cancer. It is a thermoresponsive nanosponge used for delivery of both hydrophilic and hydrophobic drugs. This nanosponge is made up of a core of poly-D, L-lactide which is loaded with a hydrophobic drug and the outer covering is made up of Pluronic-F127 which is loaded with a hydrophilic drug. The drugs can be released at the same time or the drug entrapped in the core may be released at a later time showing a prolonged release. The system is biodegradable and biocompatible, hence showing very less to no toxicity at all.
In this review, nanosponges and their synthesis, characterization, optimization and applications regarding cancer have been discussed. According to the literature, nanosponges can be classified based on their starting materials which could be polymers, metals, metal oxides, etc. Polymer nanosponges can be manufactured by methods such as melt method, emulsion method, solvent method and ultrasound-assisted method. Metallic nanosponges are manufactured by methods such as dealloying and sol-gel methods. Factors related to drugs or process parameters influence formation of nanosponges. These process parameters were used by many researchers to optimize the formulation of nanosponges to give the optimum results related to loading efficiency, particle size and encapsulation efficiency. Polymer structure also affects the formation of nanosponges. Tumors are important manifestations of cancer and provide many challenges to deliver drugs inside the tumor where dividing cells are located. These challenges can be overcome by the process of functionalization with chemical moieties or biological entities such as cell membrane fragments. Such prepared nanosponges can be characterized with many methods such as SEM and TEM which are reported in literature. Toxicity of nanosponges may be a growing concern due to their ever-increasing role in multiple industries. According to the literature, nanosponges are safe for use as a carrier. But their nanosize may alter their properties, and hence reactivity causes toxicity due to processes such as physical interaction, ROS generation and intracellular dissolution. Many methods have been reported in literature such as using antioxidants and altering the material available to reduce this toxicity.
Authors declare there are no conflicts of interest.
CD | cyclodextrin |
NS | nanosponges |
PVA | poly (vinyl) alcohol |
PBS | phosphate buffer saline |
EC | ethyl cellulose |
DMF | dimethyl formamide |
PEG | poly (ethylene) glycol |
HP-β | hydroxypropyl beta cyclodextrin |
API | active pharmaceutical ingredient |
P-gp | P-glycoprotein |
DOX | doxorubicin |
DNA | deoxy ribonucleic acid |
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\\n\\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
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\n\nWe have adopted the Protocol to increase the number of readers of our publications. All our Works are more widely accessible, with resulting benefits for scholars, researchers, students, libraries, universities and other academic institutions. Through this method of exposing metadata, IntechOpen enables citation indexes, scientific search engines, scholarly databases, and scientific literature collections to gather metadata from our repository and make our publications available to a broader academic audience.
\n\nAs a Registered Data Provider, metadata for published Books and Chapters are available via our interface at the base URL: http://mts.intechopen.com/oai/index.php
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\n\nYou can find out more about the Protocol by visiting the Open Archives website. For additional questions please contact us at ai@intechopen.com.
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The length of exposure to low oxygen pressure as well as the existing signaling pathways within different cells dictates their benefit or disadvantage from hypoxic signaling. Therefore, activation or inhibition of hypoxic intermediates could serve as novel therapeutic strategies. In this chapter, we review the role of hypoxic signaling in neurodegenerative, inflammatory, and renal disease states and the emerging therapeutic approaches involving hypoxic signaling.",book:{id:"5444",slug:"hypoxia-and-human-diseases",title:"Hypoxia and Human Diseases",fullTitle:"Hypoxia and Human Diseases"},signatures:"Deepak Bhatia, Mohammad Sanaei Ardekani, Qiwen Shi and\nShahrzad Movafagh",authors:[{id:"189604",title:"Dr.",name:"Shahrzad",middleName:null,surname:"Movafagh",slug:"shahrzad-movafagh",fullName:"Shahrzad Movafagh"},{id:"192092",title:"Dr.",name:"Deepak",middleName:null,surname:"Bhatia",slug:"deepak-bhatia",fullName:"Deepak Bhatia"},{id:"192093",title:"Dr.",name:"Mohammad",middleName:null,surname:"Sanaei Ardekani",slug:"mohammad-sanaei-ardekani",fullName:"Mohammad Sanaei Ardekani"},{id:"195341",title:"Dr.",name:"Qiwen",middleName:null,surname:"Shi",slug:"qiwen-shi",fullName:"Qiwen Shi"}]}],mostDownloadedChaptersLast30Days:[{id:"30178",title:"Chest Mobilization Techniques for Improving Ventilation and Gas Exchange in Chronic Lung Disease",slug:"chest-mobilization-techniques-for-improving-ventilation-and-gas-exchange-in-chronic-lung-disease",totalDownloads:31227,totalCrossrefCites:0,totalDimensionsCites:5,abstract:null,book:{id:"648",slug:"chronic-obstructive-pulmonary-disease-current-concepts-and-practice",title:"Chronic Obstructive Pulmonary Disease",fullTitle:"Chronic Obstructive Pulmonary Disease - Current Concepts and Practice"},signatures:"Donrawee Leelarungrayub",authors:[{id:"73709",title:"Associate Prof.",name:"Jirakrit",middleName:null,surname:"Leelarungrayub",slug:"jirakrit-leelarungrayub",fullName:"Jirakrit Leelarungrayub"}]},{id:"42773",title:"Propionibacterium acnes as a Cause of Sarcoidosis",slug:"propionibacterium-acnes-as-a-cause-of-sarcoidosis",totalDownloads:2493,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"3279",slug:"sarcoidosis",title:"Sarcoidosis",fullTitle:"Sarcoidosis"},signatures:"Yoshinobu Eishi",authors:[{id:"57567",title:"Prof.",name:"Yoshinobu",middleName:null,surname:"Eishi",slug:"yoshinobu-eishi",fullName:"Yoshinobu Eishi"}]},{id:"57668",title:"Pneumonia of Viral Etiologies",slug:"pneumonia-of-viral-etiologies",totalDownloads:3200,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Pneumonia is a common illness that continues to cause significant morbidity and mortality in both adults and children. Bacteria such as Streptococcus pneumonia, Staphylococcus aureus and Haemophilus influenzae are generally considered as the main pathogens in community-acquired pneumonia and Legionella species, Chlamydia pneumoniae and Mycoplasma pneumonia in atypical pneumonias. In contrast the proportion of pneumonias due to viruses has been both difficult to detect and quantify with any precision. However, with the advent of powerful molecular techniques and rapidly developing technologies a greater number of viruses are being implicated as pathogens and co-pathogens in pneumonia. In the case of adults, the most commonly detected viruses are influenza virus, RSV and parainfluenza. Other viruses that have recently received considerable attention, are H5N1 influenza virus and coronaviruses. Infectious causes of pneumonia in immunocompromised patients include measles, HSV, CMV, HHV-6 and Influenza viruses. Pneumonias caused by other viruses are more rarely reported and include outbreaks of rhinovirus, adenovirus (particularly serotype 14 in military institutions), coronavirus, and metapneumovirus. A range of promising therapeutic targets have been identified and numerous innovative therapeutic treatments demonstrated to improve lung injury due to viral infections.",book:{id:"5938",slug:"contemporary-topics-of-pneumonia",title:"Contemporary Topics of Pneumonia",fullTitle:"Contemporary Topics of Pneumonia"},signatures:"Al Johani Sameera and Akhter Javed",authors:[{id:"76522",title:"Dr.",name:"Javed",middleName:null,surname:"Akhter",slug:"javed-akhter",fullName:"Javed Akhter"},{id:"80162",title:"Dr.",name:"Sameera",middleName:"M.",surname:"Al Johani",slug:"sameera-al-johani",fullName:"Sameera Al Johani"}]},{id:"67117",title:"Eosinophilic Asthma",slug:"eosinophilic-asthma",totalDownloads:1265,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Eosinophilic asthma is known as a main phenotype of asthma classified on the basis of immune cells involved in inflammatory response in the respiratory airway. Eosinophilic asthma can be related to increased severity of asthma, allergic sensitization, adult onset, and increased resistance to corticosteroids. The prevalence of eosinophilic asthma is 32–40% among asthmatic patients. Different cells and cytokines are involved in its pathogenesis including eosinophil, mast cells, type 2 helper T cells, innate lymphoid cells, IL-4, IL-5, and IL-13. Eosinophil count in induced sputum and bronchoalveolar lavage is the yardstick for recognizing and distinguishing eosinophilic asthma from non-eosinophilic asthma, while various tests which are noninvasive such as fractional exhaled nitric oxide and periostin are arising as possible substitutes. Novel and advanced therapies new and advanced therapies and more convenient biological drugs, Leads to high requirement for particular endotype- and phenotype-related treatment plans. Identification and knowledge of the specific pathophysiology of eosinophilic asthma have great association with disease management and chances for better patient prognosis.",book:{id:"8738",slug:"asthma-biological-evidences",title:"Asthma",fullTitle:"Asthma - Biological Evidences"},signatures:"Bushra Mubarak, Huma Shakoor and Fozia Masood",authors:null},{id:"66258",title:"Historical Aspects of Hyperbaric Physiology and Medicine",slug:"historical-aspects-of-hyperbaric-physiology-and-medicine",totalDownloads:1575,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"The history of hyperbaric oxygen therapy (HBOT) makes for fascinating reading. From pneumatic chambers and compressed air baths to empirical therapeutic applications during the nineteenth century, the impetus to scientific application of HBOT began in seeking solution for decompression sickness during various construction ventures. French physiologist Paul Bert’s research was pathbreaking and provided a scientific explanation on the etiology of the “bends.” In 1908, JS Haldane’s experiments recommended staged decompression and made diving safe. In 1921, OJ Cunningham employed HBOT to treat hypoxia secondary to lung infections successfully. It was cardiac surgeon Ite Boerema who put HBOT on a solid footing with his open-heart surgery results in various pediatric cardiac conditions and rightly deserved the title of father of modern-day hyperbaric medicine. From 1937 onwards, HBOT research snowballed into treating a wide variety of diseases. In 1999, the Undersea and Hyperbaric Medical Society and Food and Drug Administration recognized the value of HBOT, and this led to its becoming a major tool in the armamentarium of clinicians, either as a primary or adjunctive therapy for a spectrum of diseases.",book:{id:"9126",slug:"respiratory-physiology",title:"Respiratory Physiology",fullTitle:"Respiratory Physiology"},signatures:"Chandrasekhar Krishnamurti",authors:[{id:"257885",title:"Dr.",name:"Chandrasekhar",middleName:null,surname:"Krishnamurti",slug:"chandrasekhar-krishnamurti",fullName:"Chandrasekhar Krishnamurti"}]}],onlineFirstChaptersFilter:{topicId:"1047",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82740",title:"Secondary Pneumothorax from a Surgical Perspective",slug:"secondary-pneumothorax-from-a-surgical-perspective",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.105414",abstract:"Although less frequent than the primary spontaneous pneumothorax (PSP), secondary pneumothoraces (SP) are a common clinical problem with a wide range of severity, depending on the triggering cause(s) and patient clinical condition. By definition, an SP occurs in those patients with an underlying condition that alters the normal lung parenchyma and/or the visceral pleura and determines air entry in the pleural space (e.g., COPD) or, eventually, following trauma or invasive procedures (i.e., iatrogenic pneumothorax). Less frequent, yet described, is SP occurring in neoplastic patients or infectious ones. The gravity of an SP is directly correlated to the underlying cause and patients’ clinical conditions. For example, it may be a life-threatening condition in an end-stage COPD but less severe in a catamenial related syndrome. In this chapter, we are providing a surgical overview of the most relevant and updated information on etiology, incidence, pathophysiology, and management of secondary pneumothoraces.",book:{id:"11045",title:"Pleura - A Surgical Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11045.jpg"},signatures:"Simona Sobrero, Francesco Leo and Alberto Sandri"},{id:"80875",title:"Pneumothorax: A Concise Review and Surgical Perspective",slug:"pneumothorax-a-concise-review-and-surgical-perspective",totalDownloads:42,totalDimensionsCites:0,doi:"10.5772/intechopen.101049",abstract:"Pneumothorax is the collection of air in pleural cavity, which is commonly due to development of a communication between pleural space and alveolar space (or bronchus) or the atmosphere. In this chapter, we will discuss the various aetiologies of pneumothorax, the differences in their pathophysiology and the implications on the management of the disease. The chapter focusses on the surgical aspects in the management, the revolution brought in by video-assisted thoracoscopic surgery (VATS) and the advancement of the field by introduction of uniportal VATS and robotic-assisted thoracic surgery. The principles of management of catamenial pneumothorax are revisited. The chapter also throws light on the nuances of anaesthesia techniques and the latest developments are outlined. Lastly, a section is dedicated to COVID-19 associated pneumothorax and the approach to its management.",book:{id:"11045",title:"Pleura - A Surgical Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11045.jpg"},signatures:"Shilpi Karmakar"},{id:"79289",title:"Indwelling Pleural Catheters",slug:"indwelling-pleural-catheters",totalDownloads:86,totalDimensionsCites:0,doi:"10.5772/intechopen.100645",abstract:"Indwelling pleural catheters (IPC) are now being considered worldwide for patients with recurrent pleural effusions. It is commonly used for patients with malignant pleural effusions (MPE) and can be performed as outpatient based day care procedure. In malignant pleural effusions, indwelling catheters are particularly useful in patients with trapped lung or failed pleurodesis. Patients and care givers are advised to drain at least 3 times a week or in presence of symptoms i.e. dyspnoea. Normal drainage timing may lasts for 15–20 min which subsequently improves their symptoms and quality of life. Complications which are directly related to IPC insertion are extremely rare. IPC’s are being recently used even for benign effusions in case hepatic hydrothorax and in patients with CKD related pleural effusions. Removal of IPC is often not required in most of the patients. It can be performed safely as a day care procedure with consistently lower rates of complications, reduced inpatient stay. They are relatively easy to insert, manage and remove, and provide the ability to empower patients in both the decisions regarding their treatment and the management of their disease itself.",book:{id:"11045",title:"Pleura - A Surgical Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11045.jpg"},signatures:"Yuvarajan Sivagnaname, Durga Krishnamurthy, Praveen Radhakrishnan and Antonious Maria Selvam"},{id:"79221",title:"Surgical Challenges of Chronic Empyema and Bronchopleural Fistula",slug:"surgical-challenges-of-chronic-empyema-and-bronchopleural-fistula",totalDownloads:118,totalDimensionsCites:0,doi:"10.5772/intechopen.100313",abstract:"Chronic empyema has always been a clinical challenge for physicians. There is no standard procedure or treatment to deal with the situation, and multi-modality approach is often necessary. Surgical intervention plays a very crucial role in the treatment of chronic empyema. Since bronchopleural fistula is often seen in chronic empyema patients, therefore it should also be mentioned. In this chapter, the focus will be on the different treatment options, various surgical approaches, and the rationale behind every single modality. Certain specific entity will be included as well, such as tuberculosis infection, post lung resection empyema, and intrathoracic vacuum assisted closure system application. Even with the advancement of technology and techniques, chronic empyema management is still evolving, and we look forward to less traumatic ways of approach with better outcome in the future.",book:{id:"11045",title:"Pleura - A Surgical Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11045.jpg"},signatures:"Yu-Hui Yang"},{id:"78826",title:"Pneumothorax in Children",slug:"pneumothorax-in-children",totalDownloads:94,totalDimensionsCites:0,doi:"10.5772/intechopen.100329",abstract:"Pneumothorax is a common pleural disease worldwide and is defined as the free accumulation of air between visceral and parietal pleura. Pneumothorax can be spontaneous, iatrogenic, and traumatic. Although it is less common than adults, it is seen in about 1.1–4 per 100,000 per year in the childhood age group. In patients presenting with variable clinic according to the cause of etiology, diagnosis is confirmed on a PA chest radiograph, sometimes a computed tomography may be required. The management of pneumothorax is varying from conservative, over intermediate (chest tube drainage) to invasive methods (video-assisted thoracoscopic surgery—VATS, thoracotomy). Here, we planned to write a chapter that includes a text containing general information about pediatric pneumothorax, algorithms, and visual and clinical cases of the causes of pneumothorax in children, including age, etiology, and treatment approach of pneumothorax in children.",book:{id:"11045",title:"Pleura - A Surgical Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11045.jpg"},signatures:"Hatice Sonay Yalçın Cömert"},{id:"78760",title:"Bronchopleural Fistula after Pulmonary Resection: Risk Factors, Diagnoses and Management",slug:"bronchopleural-fistula-after-pulmonary-resection-risk-factors-diagnoses-and-management",totalDownloads:234,totalDimensionsCites:0,doi:"10.5772/intechopen.100209",abstract:"Bronchopleural fistula (BPF) after a pulmonary resection is rare with some of the most life-threatening consequences and a high mortality rate. Contamination of the pleural space resulting in empyema and spillage of the infected fluid into the remaining lung leading to respiratory distress remain the biggest concerns with BPF postoperatively. There are many patient characteristics and risk factors that can be evaluated to decrease the chance of a postoperative BPF. Presentation of BPF can be early or late with the late BPF more difficult to diagnosis and manage. Many options to treat BPF include surgical repair, conservative management, and endoscopic treatment.",book:{id:"11045",title:"Pleura - A Surgical Perspective",coverURL:"https://cdn.intechopen.com/books/images_new/11045.jpg"},signatures:"Kristina Jacobsen"}],onlineFirstChaptersTotal:8},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. 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