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Microemulsions are lipid based drug delivery system consisting of oil, water, surfactant and often a co-surfactant. They are prepared in order to deliver the drug in an effective manner so as to obtain the desired therapeutic activity. Compared to other conventional therapy, they can deliver the drug in an efficient manner because of their characteristics like reduced particles size, lipid based drug delivery system, thermodynamic stability and economical scale up. Anti-cancer drugs can be easily incorporated into microemulsion so as to target the cancer cells. This helps in increasing the solubility, permeability and absorption of the poorly soluble and poorly permeable drugs, thereby helping in enhancing the bioavailability of the drug. In this chapter, we are also focusing on the herbal based formulations that will be helpful in effectively fighting against cancer cells with less or no side effects. A light has also been shed on the advantages and disadvantages of the microemulsions that will be helpful in considering them as an effective model to conquer cancer and promote the same in the upcoming years.
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, India
Raman Sureshkumar*
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, India
S.P. Dhanabal
Department of Pharmacognosy and Phytopharmacy, JSS College of Pharmacy, JSS Academy of Higher Education and Research, India
*Address all correspondence to: sureshcoonoor@jssuni.edu.in
1. Introduction
Microemulsions are lipid based drug delivery system consisting of oil, water, surfactant and often a co-surfactant. They are prepared in order to deliver the drug in an effective manner so as to obtain the desired therapeutic activity [1]. Compared to other conventional therapy, they can deliver the drug in an efficient manner because of their characteristics like reduced particles size, lipid based drug delivery system, thermodynamic stability and economical scale up [2]. Anti-cancer drugs can be easily incorporated into microemulsion so as to target the cancer cells [3]. In this chapter, we are also focusing on the herbal based formulations; this will be helpful in effectively fighting against cancer cells with less or no side effects. The advantages and limitation of the microemulsions discussed in this chapter will also be helpful in considering them as an effective model to conquer cancer and promote the same in the upcoming years.
As said earlier, the microemulsions are lipid based drug delivery systems that are involved in effectively delivering the drug to the target site [4, 5]. The term microemulsions were employed by T.P. Hoar and J.H. Shulman in 1943 [6]. The word microemulsion was also called as transparent emulsion, solubilized oil and micellar solution etc. The microemulsions are optically isotropic in nature and they are also thermodynamically stable. It has been stated that according to IUPAC the diameter of the particle can approximately vary from 1 to 100 nm that can be usually between 10 and 50 nm [7]. Basically the microemulsions can be divided into oil in water (O/W) type, water in oil (W/O) type and bicontinuous microemulsion with high solubilizing power [8, 9]. The different types of microemulsion are given in Table 1.
Table 1.
Representing different types of microemulsions.
While coming to the theories of microemulsion, there are basically three theories as follows:
Interfacial theory: Also called as mixed film theory or dual film theory. In this the microemulsion are formed spontaneously by a complex film formation at the oil water interface by the surfactant and co-surfactant. These two compounds are further helpful in decreasing the interfacial tension. Thus, forming a microemulsion [10].
Solubilization theory: They are usually depicted by the phase diagram by considering components of microemulsion including oil, water and surfactant [11].
Thermodynamic theory: The thermodynamic properties of microemulsion like free energy, interfacial tension and surface tension are interdependent on each other. It states that spontaneous emulsification is involved in the formation of microemulsion with negative free energy that makes the emulsion thermodynamically stable [6, 12].
2. Composition and method of preparation of microemulsion
2.1 Composition of microemulsions
Basically, the mircoemulsion consists of three main ingredients including water, oil and surfactant.
2.1.1 Water phase
Aqueous phase plays an important role in the formulation of microemulsion. Based on the type of microemulsion, they act as either a dispersion medium or a dispersed phase in the microemulsion [13]. This phase can accommodate the hydrophilic active drug and some of the preservatives. Sometimes they are also replaced by the buffer solution. In case of water in oil microemulsion, the addition of the water makes changes in the concentration of the surfactant/ water ratio. Dilution of the microemulsion further with the water leads to the phase separation thus, disrupting the droplet formation. Hence, in order to obtain a stable microemulsion, the accurate water ratio must be employed [6].
2.1.2 Oil phase
They are the most important component in the microemulsion system to solubilize and transport the lipophilic compounds via the lymphatic system. It also increases the GI (gastrointestinal) absorption of the drug. The selection of oil is determined based on the solubility of the drug in that particular oil. Example of oil includes olive oil, castor oil, capryol 90, oleic acid and isopropyl myristate etc. [6, 8, 14].
2.1.3 Surfactants
They are usually employed in order to decrease the surface tension as well as the interfacial tension. Since, they contain both the lipophilic as well as hydrophilic character; they have the affinity towards both the polar and the non-polar phase. When the aqueous phase is more compared to the oily phase, then the interface between the oil and aqueous phase will curve spontaneously towards the water leading to the formation of oil in water structure. Whereas, when the lipophilic group is more bulky than that of aqueous phase, then the interface will curve towards the opposite direction leading to water in oil microemulsion [15]. In brief the different types of surfactants used in microemulsion are given in Table 2. While coming to the type of surfactant, they can be divided into the following:
Non-ionic surfactant: This type of surfactant produces less irritation. Thus, they are useful in oral administration. Example includes cremophor, polyoxyethylene sorbitol hexaoleate [16], and tween 20 [17].
Cationic surfactant: Their surface is positively charged. But, as compared to the anionic surfactant, they are more irritating. Example Cetalkonium chloride and benzalkonium chloride etc.
Anionic surfactant: They are negatively charged and possess the ability to penetrate into the skin. Example includes sulphonates, sulphates, and phosphates [8].
Zwitterionic: They are otherwise called as amphoteric surfactant, which contains both positive as well as negative charge that contributes to their neutral charge at neutral pH [18]. Example includes betaines and amphoacetate class compounds.
Table 2.
Indicating the types of surfactants.
2.2 Preparation of microemulsions
Microemulsions can be prepared by the following methods:
Phase titration method: In this method, the microemulsion is formed by the spontaneous emulsification method. The phase diagram is useful in determining the various interactions that happens when the components of the microemulsion is being mixed [19]. Mainly from the phase diagram, the microemulsion region can be determined [20]. Later, the optimized formulation can be obtained by implementing any of the experimental models [21, 22].
Phase inversion method: While coming to the phase inversion method, the microemulsion undergoes phase inversion on addition of excess dispersed phase. During this, change in the particle size occurs that can affect the drug release both in-vitro as well as in-vivo [23]. In this case, when the non-ionic surfactant is used for the preparation of microemulsion, the change in temperature decides the formation of the microemulsion by the method called phase inversion temperature (PIT) method. Suppose when there is an increase in temperature, it leads to the water in oil microemulsion, whereas when the temperature decreases it leads to oil in water microemulsion [24]. While coming to the phase inversion composition, the addition of the water or oil makes the difference [25]. In which, when water is added to oil phase or oil is added to water phase, the surfactant exhibits both the hydrophilic and lipophilic property at one point, and that point is called as emulsion inversion point. After which an addition of water or oil makes the changes in the curvature of the microemulsion and leads to the formation of o/w microemulion or w/o microemulsion [26, 27, 28].
3. Herbal based microemulsion for cancer treatment
Various herbal based components are being tested by researchers for determining the anti-cancer activity. But some of the components have low bioavailability because of low solubility. Thus, the microemulsion acts as a carrier for the delivery of such components and helps in improved bioavailability and resulting in enhanced therapeutic effect [29].
Dibenzoylmethane (DBM) is one such compound that has poor water solubility because of which they have low bioavailability. In order to overcome this condition, DBM has been incorporated into microemulsion [30]. The microemulsions are also capable of protecting the drug molecule form enzymatic hydrolysis and oxidation etc., thus allowing the drug to reach the target site. In the study conducted with DBM, peppermint oil has been used and oil in water microemulsion has been made because of poor solubility of DBM in water. This is one of the advantage of microemulsion were both the hydrophilic as well as hydrophobic drug can be incorporated into them. This formulation has exhibited its action as effective chemopreventive agent in forestomach tumor. It has also been stated that the microemulsion decreases the interfacial tension between the vehicle and the intestinal cells and leads to enhanced permeation. This can eventually result in increased therapeutic activity [31].
There are also many medicinal values present in the food compounds that we consume in our day to day life. One such compound is turmeric. The turmeric which is also known as Curcuma longa L. (C. longa) possesses various biological activities like anti-cancer, anti-oxidant and anti-inflammation etc. [32]. Various studies have been carried out with curcumin on different cancer cells like melanoma, prostate, hepatoma and breast cancer cells. Yen Chu Chen et al. has worked on curcuminoid microemulsion to improve the inhibitory effect on the colon cancer cells. The microemulsion has been prepared by soya bean oil, anhydrous ethanol (co-solvent) and tween 80. Both the early and late apoptosis has been observed in cancer cells and also the cell cycle arrest at S phase. Additionally, the up regulation in p53 (tumor suppressor) has been observed in the p21- independent manner. Increase in caspase 8, caspase 9, and caspase 3 have also been observed. Thus, it can be said that curcumin can produce a wide range of anticancer activity by focusing on extensive mechanism [33].
As said earlier even though various natural compounds are available for the rehabilitation of cancer, they fail to produce the complete desired action because of low bioavailability and poor solubility. Thus, microemulsion helps in enhancing the bioavailability and improving the solubility with the aid of their lipid based drug delivery system. One such study has been carried out by Salma A. El-Sawi et al., to improve the delivery of the extracts of Salix mucronata that possesses anti-proliferative activity. The extracts from the Salix mucronata has been loaded into the microemulsion, so as to improve the penetration of compounds through the biological barriers and produce a desired pharmacological action with less quantity of dose [34].
When a drug is having low solubility in water but lipophilic in nature, it will be loaded into the microemulsion because of its lipid based delivery. Additionally, because of the lipid based drug delivery, they not only improve the solubility, it can also enhance the permeability of the drugs through various barriers. In which the blood brain barrier (BBB), one of the strongest barriers which do not allow the entry of drugs into the target site, acts as a main hurdle for various drugs in targeting the brain tumor [35]. Even though various flavonoids, terpenes, and carotinoids are being studied to determine their anti-cancer activity, most of them fail to reach the target site because of BBB. Thus, it is important to breach the BBB to get a therapeutic activity. Most of the techniques for delivery of the drug into the brain by crossing the BBB involves invasive or a semi-invasive technique, whereas the nasal route of drug delivery acts as a non-invasive method. But the direct administration of active ingredient into the nasal cavity may lead to degradation of drug by various enzymes and clearance of drug. Thus, in order to overcome these drawbacks, the microemulsion can be used as carrier because of their property to improve the permeability of the drug [36, 37].
Quercetin is a flavonoid that has been widely studied for their anti-cancer activity [38]. They have the ability to inhibit the proliferation of various cancer cells like lung, prostate, liver, breast, cervical and colon cancer [39]. Quercetin is also being used as a synergistic agent along with other chemotherapeutic drugs [40]. But because of their low permeability, they are unable to reach the target site and produce a complete therapeutic activity. Thus, if they are being loaded by any of the carrier or drug delivery system, one can meet the expected outcome. Sagar Kishor Savale in 2017, has prepared the quercetin microemulsion, in order to target the brain tumor assuming that this carrier would help in increasing the permeability of the drug. Quercetin has been dissolved in oleic acid and later tween 80 and polyethylene glycol 400 has been used as surfactant and co-surfactant respectively for the preparation of microemulsion. Though the in-vitro permeability study has been done, the in-depth molecular mechanism and in-vivo studies should be determined [41].
Another flavonoid that is helpful in targeting the cancer cells is myricetin. It is also structurally similar to that of quercetin and luteolin. Myricetin exhibits anti- cancer activity [42] by interacting with various oncoproteins like Janus kinase –signal transducer and activator of transcription 3 (JAK1-STAT3), protein kinase B (PKB) and mitogen activated kinase 1 (MEK 1). They also act on the over expressed cyclin- dependent kinase 1 to exert an anti-mitotic effect on the liver cancer cells [43]. Though, they exhibit various anticancer activities, the main struggle comes when there is low bioavailability. But this problem can be eradicated by using microemulsion. Studies are also being carried out for the preparation myricetin microemulsion that can improve the bioavailability of the compound [44]. Shujun Wang et al. have formulated myricetin microemulsion for oral delivery. It was stated that the incorporation of microemulsion delivery system could decrease the dose of the myricetin because improved drug availability at the target site. Since, the microemulsion is involved; the author says that the enhanced bioavailability of myricetin at the target site may because of the presence of payers patch and the M (Microfold) cell in the intestine and also because of the presence of lipid in the microemulsion, which makes the enhanced absorption via the lymphatic system [45].
Ruixue Guo et al. has prepared a myricetin microemulsion, for enhancing the bioavailability of the compound, anti-proliferative activity and also the anti-oxidant activity. In this study, the effect of myricetin microemulsion was tested on the liver cancer cells (HepG2). Since, the excess addition of surfactant in the microemulsion may lead to toxicity, it is important that we need to use the surfactant in the minimum quantity. Thus focusing on these criteria, the work has been carried out by screening various oils, surfactant and co-surfactant to get stable and optimized formulation. As a result of it, labrafac lipophile WL 1349 was selected as oil phase, tween 80 and cremophor RH 40 was used as surfactant and transcutol HP has been used a co-surfactant. The prepared miroemulsion has shown enhanced oral bioavailability as compared to that of the myricetin suspension (Sodium carboxy methylcellulose suspension) [46].
The microemulsion can also be a self-micro-emulsifying drug delivery system (SMEDDS). They are given as a preconcentrate so that after reaching the target site, they may get converted into a microemulsion giving a prodrug effect. The advantage of such delivery system is that, the stability of the formulation can be maintained as a result the bioavailability can also be improved. In the SMEDDS, the lipid phase used can also be liquid or solid. While comparing both, it has been said that S-SMEDDS (i.e.): use of solid lipid is preferred because, it involves the solidification of liquid excipients into a powder form (solid form) that helps in obtaining a more stable formulation compared to liquid lipid. One such solid SMEDDS has been prepared by Wenli Huang et al. [47]. In this work, Brucea javanica oil is being loaded into S-SMEDDS (BJOS) to enhance the anti-cancer activity. Brucea javanica oil is a traditional herbal medicine in China that has the ability to treat various cancers like gastrointestinal cancer, lung cancer and prostate cancer. Since, the oil itself is producing various anti-cancer activity, they were used as a main component in the study that can act as the anti-cancer agent. The BJOS formulation was prepared by using Brucea javanica as oil phase, Cremophor RH40 and PEG 6000 as surfactant and co-surfactant respectively. Compared to the Brucea javanica oil emulsion alone, the BJOS formulation had a better anti-proliferative activity. This may be because; the S-SMEDDS would have carried the BJO into the cancer cells via endocytosis.
Apart from the above said compounds, there are also other herbal compounds that exhibits anti-cancer activity by acting on various pathways by inhibiting the cell cycle arrest, maintaining the genetic stability, inducing apoptosis exhibiting anti-angiogenic activity and also anti-metastatic activity. Thus, as a nutshell, it can be said that it would be a better option if we choose microemulsion as a drug delivery system or a carrier for the delivery of herbal compounds that exhibits anti-cancer activity. Because unless the conventionally available drugs or synthetic drugs, the herbal compounds may not cause much side effects or harm the normal cells. Even the herbal compounds are also being taken by us on regular basis. Thus, it will lead to great endeavors if natural compounds are being delivered in an accurate manner by using this kind of delivery system.
4. Different routes of administration of microemulsion
4.1 Oral route
As it was already said that the solubility of the drug plays an important role in bioavailability of the drug, it is important to improve the solubility so as to increase the bioavailability (Figure 1). When a drug is being incorporated in microemulsion, compared to conventional medications, the microemulsion can increase the absorption, increase the therapeutic efficacy and also decrease the drug toxicity [12]. Apart from the solubility, in many of the cancers, the MDR (multi drug resistance) plays an important role; it does not allow the anti-cancer drugs to produce its activity by creating an efflux system. But, the microemulsion has the capacity to overcome this efflux system and deliver the anti-cancer drug in a more efficient manner. One such study has been carried out by Ding Qu et al., in which a multicomponent microemulion has been formulated consisting of coix seed oil, ginsenoside Rh2 loaded with etoposide. This formulation has been useful in inhibiting the Pgp-efflux, which may because of the use of G-Rh2 that has the capacity to interact with the Pgp-efflux and in addition, the formulation has produced a synergistic activity which may be because of the oils used in this formulation, that also possess some anti-cancer activity [48].
Figure 1.
Represents the different routes of administration of microemulsion for targeting various cancers (Created with Biorender).
Apart from the normal microemulsion, the microemulsion can be used as a preconcentrate in order to improve the bioavailability as well as therapeutic effect of anti-cancer drug. As it was said already, one such form of preconcentrate is called the Self-microemulsifying drug delivery system (SMEDDS). They are also similar to that of micro-emulsion, whereas being a preconcentrate, they does not have water in their formulation. During this case a question arises in our mind stating that were does the aqueous phase come from. Well, the SMEDDS being a preconcetrae when administered, it gets emulsified with the help of Gastro intestinal fluid, thereby forming a microemulsion. This type of self-emulsifying microemulsion serves more advantage as compared to the existing microemulsion. Since, the water is not involved, enhanced physical and chemical stability can be obtained on long term storage [49]. It also has the ability to decrease the gastric irritation caused by some of the anti-cancer agents. Studies are also being carried out with SMEDDS for the rehabilitation of cancer. Triptolide obtained from Tripterygium wilfordii possess anti-cancer activity, at the same time they also have low solubility, gastrointestinal irritation and also poor bioavailability. Triptolide has been incorporated to SMEDDS in order to overcome the above said effects and their anticancer activity on gastric cancer has also been identified [50].
4.2 Parentral route
Microemulsion can be delivered via the parenteral route instead of suspension that is not suitable for the parenteral route. Compared to liposomes, they are having a good stability when given through parenteral route. When a microemulsion is loaded with the higher concentration of the drug, the frequency of administration can be decreased [51]. Some of the drugs have to be given through the parenteral route because in order to overcome the degradation of the drug, instability of the drug, low bioavailability of the drug, decreased therapeutic activity of the drug due to oral administration. At some instance, the parenteral route of administration of the drug itself can lead to precipitation of the drug when mixed with the infusion fluids. Thus, in those cases it is important to incorporate the drug into a suitable vehicles or carrier to obtain an improved bioavailability an increased therapeutic activity without any capillary blockade. But incorporation of more solvents or aqueous solutions may cause mild to severe side effects. In these circumstances, the microemulsion comes into play, because of their thermodynamic stability. Jayesh Jain et al. has worked on etoposide, in which they have formulated the microemulsion for parenteral administration. Since, the etoposide need to be administered slowly through the intravenous infusion, it is important to detect the changes when they are mixed with infusion fluids. As a result they observed that the microemulsion was not having a drug precipitation up to a certain concentration of drug. But as the concentration of drug increases the precipitation serves as a limitation. Thus, more study on the reason for the drug precipitation should be understood [52].
The microemulsion also serve various advantages while comparing other colloidal carriers, microemulsions can deliver the hydrophobic drugs, as they can solubilize those types of drugs and also the scale-up can be done easily compared to other carriers.
It is important to know the right excipients for the preparation of microemulsions for parenteral delivery, as the parenteral delivery deal with only few excipients. Those excipients should also be biocompatible, non- irritant and a sterilizable one. Other than these properties, the excipients that are used for preparation of microemulsion for parenteral delivery is similar to that of the normal microemulsion. They consist of oily phase, surfactant, co-surfactant and the aqueous phase. But while using these components during the formulation, certain factors should be considered like [53]:
Long term usage of oily phase for parenteral administration should be determined.
Certain surfactants like polyoxyethylene alky ethers may cause hemolysis at higher concentrations. So, the concentration of this type of surfactants must be considered.
The use of polyethoxylated castor oil which has to be used with caution because of their ability to cause serious adverse effects.
The use of propylene glycol as co-surfactant at higher concentrations my cause pain at the injection site and also hemolysis.
4.3 Nasal route
Glioblastoma, or brain tumor, is the condition, which is very difficult to target by various anti-cancer drugs. The administration of drug through oral route may not guarantee that it will deliver most of drug to the target site. And also most of the available techniques for targeting brain tumors are either invasive or semi-invasive. Thus, it is important to deliver a drug in such a way that it can reach the target site without being invasive in nature and also improve the bioavailability with enhanced therapeutic activity. Nasal route of administration comes into play at these situations. It is one of the non-invasive techniques that can bypass the BBB. When a drug is being administered intranasally, they can enter into the brain or target site depending upon the nature of the drug, type of formulation and the physiological conditions. The different pathways of entry of drug are [54]:
Olfactory nerve
Trigeminal nerve
Lymphatic pathway
Cerebro spinal fluid (CSF)
Vascular pathway.
Various flavonoids like curcumin [55] and rhein [56] are also been administered via intranasal delivery to study the effect of these compounds on glioblastoma, as they already possess various anti-cancer activity, anti-oxidant activity and anti-inflammatory etc.
It has also mentioned in previous studies that the uses of microemulsion for the intranasal delivery are safe and effective. And moreover, since the nasal route helps in direct delivery of drug to the target site than entering into systemic circulation, the concentration of drug at the target site can be increased along with the use of microemulsion [57]. The concentration of various drugs have been improved at the target site with the help of microemulsion and some of them include albendazole sulfoxide that possess anti-proliferative activity [58] and teriflunomide that also possess anti-cancer activity [59, 60, 61].
The administration of drug through nasal route may be prone to mucociliary clearance. Thus, in this case the drug or the formulation may not be able to reach the target site and produce its therapeutic action. Thus, for this purpose, the mucoadhesive agents are being used that can slow down the mucociliary clearance [62]. Because of the enhanced penetration property of microemulsions through biological membranes, they are being used to deliver the drug through nasal cavity [63]. Thus, the use of mucoadhesive agents to the microemulsion can improve the retention time and increase the absorption of drug. Julio Mena-Hernández et al. have formulated mebendazole microemulsion containing mucoadhesive agent namely sodium hyaluronate for intranasal delivery to target the glioblastoma. It was stated that the treatment with the formulation has increased the survival time in animals and also decreased nasal toxicity has been observed [64].
4.4 Topical route
Topical route is one of the alternative approaches over the oral and parenteral route. This is one of the non-invasive methods of drug delivery system [65]. They are also convenient route of drug delivery. They are also helpful in overcoming various limitations that are being produced by oral route like gastrointestinal degradation of drug, hepatic clearance, toxicity and finally decreased bioavailability. Though the topical route have several advantages, they also have certain disadvantages like low permeability though the skin, decreased residence time on skin, the viscosity of the formulation, spreadability of the formulation etc. But these problems can be conquered with the aid of microemulsion. They have the capacity to permeate through the skin, improve the solubility of the drug and also enhance the absorption of the drug. Various drugs are being incorporated into the microemulsion because of these properties [66]. Example Methyl dihydrojasmonate that has the capacity to produce anti-tumor activity is being incorporated into microemulsion and studied. Targeting solid tumors by transdermal delivery is in emerging stage. This allows convenient way of targeting the tumor and also overcome the first pass metabolism produced by the oral dosage forms. The Methyl dihydrojasmonate that has been incorporated in microemulsion has been studied on MCF-7 cancer cell and Ehrlich solid carcinoma model [67].
The non-toxic and non-irritant property of microemulsion makes them suitable to treat skin cancers. 5- Fluorouracil has been used for treating skin cancer. But they have a major disadvantage of poor skin permeation. Thus, in this case they are being incorporated into microemulsion for improving the permeability of the drug. So that it can produce its anti-cancer activity [68]. 5-fluorouracil is being studied by many of the researchers by incorporating them into a microemulsion for rehabilitation of skin cancer [69]. Thus, opting for a microemulsion would be a good strategy for the treatment of skin cancer and solid tumors.
Apart from the microemulsion, the incorporation of microemulsion into gel also plays a vital role. It further increases the residence time of the drug on the skin and also release of the drug on the target site is prolonged [70].
Some other microemulsions that are studied by various researchers for anti-cancer activity is given in Table 3.
Can be administered through various routes like oral, parenteral, topical and intranasal.
Increase in patient compliance due to liquid dosage form.
5.2 Disadvantages of microemulsion
Large quantity of surfactant and co-surfactant usage may lead to toxicity issues [76].
It’s a doubt when it comes to sustained drug release [78].
Due to the precipitation of the drug, they should be used in infusion or parenterals after careful investigation of nature of the drug and the microemulsion character.
Since, there is a toxicity issue with surfactant, the surfactant should fall under the “Generally-Regarded-as-Safe” (GRAS) class [79].
Microemulsions are the lipid based drug delivery systems that are being studied by a wide group of researchers. Even though the microemulsion has various advantages like loading of both hydrophilic and lipophilic drug, thermodynamic stability and improved patient compliance etc. They lack behind when it comes to the surfactant concentration. The main ingredient used to decrease the interfacial tension between the oil phase and aqueous phase is surfactant and the co-surfactant. Being the main ingredient, they may be used in large quantity. This turns out to be one of the major disadvantages, which thereby leads to toxicity. Usually only 40% of the surfactant should be used in the formulation. Thus, a suitable surfactant that is capable of decreasing the interfacial tension at a low concentration must be employed in the formulation [80]. The microemulsions are usually suitable for scale up process, which is more important from industrial point of view that can be done at a low cost. Apart from the treating various cancers and diseases, the microemulsions are also being used for the cosmetic formulations [81], because of their increased permeability and action on the skin for a prolonged period of time. Though they are being used for various route of delivery for treating a wide range of cancer, the surfactant concentration should be considered which plays a major role in deciding the fate of microemulsion.
Microemulsions are lipid based drug delivery system that comprises of oil, surfactant and a co-surfactant. This can solubilize both the hydrophilic as well as lipophilic drugs. Thus, helps in increasing the absorption and bioavailability of the drugs. Since, the bioavailability is increased; the desired therapeutic activity can be obtained with minimum dose of the drug. Thu, we can also overcome the toxicity due to higher dose of the drug. Most of the herbal compounds like flavonoids, terpenes and caratinoids are possessing the anti-cancer activity. But only because of their poor solubility and poor permeability, they are not being widely studied for conquering cancer cells. This fate of herbal compounds can be changed once they are being incorporated into a safe and effective carrier or vehicle. Even though various carrier systems are available and being studied widely by researchers, the microemulsion plays a vital role and standalone compared to others because of their property like thermodynamic stability, increasing the solubility and permeability of drug and also easy scale up process. They act as a stalwart supporter in the delivery of potential anti-cancer compounds, without affecting the nature of the drug and maintaining their stability by overcoming various hurdles like GI (Gastrointestinal) degradation, first pass metabolism and also toxicity due to higher dose of the drug. Thus, as a nutshell it can be said that the microemulsions are prominent carriers in delivering the effective anti-cancer drug and also responsible for increasing the patient compliance and enhancing the therapeutic activity. But, apart from this, the limitations of the carrier should also be taken into consideration, like use of desired oil, surfactant and co-surfactant as well as their concentrations. By meticulously pondering the above points, one can develop an effective formulation for the rehabilitation of the cancer with the aid of microemulsions.
The authors would like to thank Indian Council of Medical Research (ICMR), New Delhi for awarding Senior Research Fellowship (SRF)-“3/ 2/2/2/2020-NCD-III.” The authors would like to thank the Department of Science and Technology – Fund for Improvement of Science and Technology Infrastructure in Universities and Higher Educational Institutions (DST-FIST), New Delhi for their infrastructure support to our department.
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Written By
S.K. Janani, Raman Sureshkumar and S.P. Dhanabal
Submitted: 23 July 2021Reviewed: 03 November 2021Published: 28 September 2022
Open access peer-reviewed chapter
