Drug Delivery of Corticosteroids

Abstract

In this chapter, we will study how we were able to place drugs from the family of corticosteroids in the places where the drug is intended to be affected during the surgery. It was also possible to control the release of accumulated quantities of dexamethasone by coating it with some soluble polymers such as chitosan. We used samples of bioglass grafted with chitosan polymer to which different percentages of dexamethasone (Dexa) were added (5, 10, and 15%). In addition, the cumulative doses emitted from the samples were calculated by means of statistical functions and using the ultraviolet device. This was also tested on the plasma fluid of the human-simulating body fluid (SBF), and it was confirmed that the appropriate amounts of Dexa were emitted over a period of (1, 2, 4, 8, 16, 21, and 33) days. Due to its shown efficacy in simulating in liquid of the human body (SBF), we aim to put it within the human body as soon as feasible.

1. Introduction

Corticosteroid drug delivery is a brand-new, fast-developing area in medical research. A corticosteroid-like dexamethasone is a suitable bioactive compound that may be used in bone tissue engineering applications. However, using drug delivery technology today is known to be crucial because it prevents the medications from passing through GIT. Additionally, this medication may be used in an osteogenic medium to encourage the development of stem cells that follow the osteogenic lineage [1, 2, 3].

Biodegradable polymers are thought to be the best choice for biological applications in tissue engineering and drug delivery, where the characteristics of bioactive glass can be enhanced and drug release patterns can be changed when polymers are utilized in bioactive glass/polymer composites. Accordingly, to increase patient compliance, the capacity of long-term medication administration for treating chronic illnesses would be crucial. By utilizing bioactive glass/polymer composites, various medications may be locally released and drug delivery systems already have employed a variety of medications, including anti-inflammatory, osteogenic, anticancer, and antibiotics [4, 5]. The characteristics of bioactive glass can be enhanced and drug release patterns can be changed when polymers are utilized in bioactive glass/polymer composites [6]. Due to the widespread usage of dexamethasone as anti-inflammatory medicine, we attempted to create a novel drug delivery system based on (chitosan and bioglass) [7].

This study aims to create and describe solid lipid nanoparticles (SLNs) loaded with Dexa-P and compare them to other drugs with a similar structure or lipophilicity demonstrating that utilizing Dexa-P increases medication loading in SLNs. The development of the standard operating procedure for preparation allowed for evaluation of the size, form, structure, and crystallinity of SLNs.

2. Drug delivery systems (DDS)

2.1 Definition

Technologies that release medications and bioactive chemicals are referred to regarded as “drug delivery” in general (e.g., proteins, growth factors, lipids, genes) [8] . Typically, it involves a substance that delivers the medication to the targeted area and keeps the therapeutic agent there. This substance is frequently referred to as the system’s carrier or matrix. The idea of controlled release has, more often than not, been closely linked to the idea of medication delivery. A medicinal drug is delivered and released in a time-dependent way under the term “controlled release.” This continuous release is necessary since it influences the dosage that a patient should take and how quickly an organism absorbs the medication [9, 10].

2.2 Therapeutic window

The boundaries between the minimum toxic concentration (MTC) and the lowest effective concentration are known as the therapeutic window (MEC). MTC serves as an upper limit since it is the lowest concentration necessary to cause a living thing to exhibit hazardous behavior. MEC, on the other hand, functions as a lower limit since the intended effect is produced at the minimal concentration. Therefore, to sustain the medicine’s efficacy without causing a hazardous reaction, the drug concentration must constantly remain within the therapeutic window [11].

2.3 Historical perspective

The first implant, released in 1989, disperses goserelin acetate over a one- to three-month period. Less than 10 clinical treatments that deliver additional peptides and proteins have since been developed, highlighting the challenges in product development. The second generation’s final 10 years were devoted to the creation of medication delivery devices based on nanotechnology. The technologies indicated in Table 1 represent the second generation of drug delivery, which has not yet been created. However, in order for the third generation of medication delivery to be successful, it must address and get over the problems that the first two generations of drug delivery systems have. The three generations of medication delivery are listed in Table 1. Smith Kline & French developed the first controlled release medication in 1952 for dextroamphetamine distribution over a 12-hour period (Dexedrine) [12].

Table 1.

Evolution of controlled drug delivery systems.

2.4 Future back

It is impossible to forecast the developments in medication delivery technology that will occur over the next 30 years. No matter what new technologies are created, our existing demands for treating illnesses and overcoming obstacles to better medicine delivery will remain the same. The issues described will need to be resolved by more advanced medication delivery technology (Table 1).

As the number of people with diabetes keeps growing, there will be a greater need for designing modified insulin delivery devices. Since more than 10 years ago, targeted medicine delivery to tumors has been a major area of study. This demand will not go away overnight. To increase patient compliance, the capacity of long-term medication administration, that is, 6 months or longer, for treating chronic illnesses, would be crucial. Additionally, novel in vitro testing techniques will need to be created to precisely forecast the human in vivo pharmacokinetics of medicines and drug formulations. Scientists working on drug delivery can wait and see what new technologies are created in the future to address the current issues. But with this passive attitude, we will not be able to meet our objectives in a timely manner. Instead, medicine delivery researchers might use a daring new strategy called “future back.” The future back method focuses on comprehending what is plainly achievable or impossible rather than trying to imagine the future to discover a means to accomplish a goal. Scientists will only be able to advance to the level of the norms and priorities of that period if they rely on future inventions that have not yet been created. This is particularly true when innovations are in small scale and soon become obsolete [13].

To reach the aim, scientists may specify what innovations are required and how to combine those breakthroughs to create the perfect drug delivery system. This allows them to start by describing an ideal drug delivery system with all desirable qualities.

At least four modified delivery mechanisms will be developed during the third generation. The targeted delivery of anticancer drugs or siRNA to tumors, the glucose-sensitive transient insulin delivery with on-off switching capability, the long-term drug delivery ranging from 6 months to 1 year, and in vitro testing techniques that can predict in vivo pharmacokinetic profiles are among them. Technically speaking, creating a modified insulin delivery system, is the most difficult of them.

Delivering insulin is distinct from administering other medications in that it must be administered at the appropriate moment, that is, when the blood glucose level rises, and in a precise quantity that is just sufficient to lower the blood glucose level. The insulin level in the blood should pulse rather than remain constant, as seen in Figure 1. Following a drop in glucose levels, the blood’s insulin concentration should also drop.

Figure 1.

Therapeutic window are the limits between the minimum toxic concentration (MTC) and the minimum effective concentration (MEC). Single-dose drug concentration in the plasma (blue solid line), multiple-dose drug concentration in the plasma (dotted line), and zero-order controlled release (green solid line) in the therapeutic window. The range in which a pharmacological dose is effective without having a toxic impact is defined as the area between the minimum toxic concentration (MTC) and the minimum effective concentration (MEC).

Hypoglycemia will happen otherwise. Pulsatile drug release systems that are practical for clinical applications still need to be developed despite substantial advancements [14].

2.5 DDS advantages and disadvantages

2.5.1 Advantages

Increasing the drug’s bioavailability and duration of effect.

Little medication loss and degradation.

Preventing harmful medicine side effects.

Lowering the dosage frequency.

Medication consumption is improved and drug concentration variations are minimized in plasma levels.

Patient compliance has improved.

2.5.2 Disadvantages

Products of harmful degradation.

Patients’ pain with the use of the DDS device necessitates surgical Intervention, either for the installation or removal of systems.

High price of the finished item.

2.6 Mechanisms of drug release

There are a number of ways that a substance might release a drug; here, we will concentrate on the most common ones. The two primary categories of these mechanisms are non-responsive and responsive. Non-responsive systems, in which the therapeutic agent is released as a result of matrix swelling or disintegration, do not require an external stimulus to deliver a medicine. The following is a list of ineffective methods [15].

2.6.1 Diffusion mechanism

It is based on how water (from bodily fluid) and the matrix where the medicine is loaded interact. Monolithic and reservoir matrices are the two types of matrices that adhere to this principle. This carrier is referred to be a monolithic matrix if the medicine is evenly distributed throughout the matrix and is able to diffuse via the pores when the matrix breaks down. If not, the matrix is categorized as a reservoir because the medication is disseminated through a coating layer that covers its surface. The superficial layer in reservoir matrices therefore regulates the release kinetics. Typically, both systems exhibit a burst release followed by zero-order kinetics.

2.6.2 Controlled osmosis

Osmotic pressure acts as the driving force to disperse the drug outward from the matrix when the difference in drug concentration is between the matrix and the surrounding fluid. The kinetics of this process frequently has zero order.

2.6.3 Ionic exchange

It is connected to ionic medications that replenish ions in live tissue via a concentration gradient or it is associated with ionic drugs that restore the ions in living tissue along a gradient of concentration.

2.6.4 Erosion mechanism

It is dependent on the matrix’s degradation. It is divided into two stages:

Therapeutic compounds can then be released under zero-order kinetics after the matrix has first undergone a superficial degradation. As the matrix dissolves over time and the bulk degrades with time, drug release is also facilitated. Sensitive medications may often be supplied primarily in the target tissue and avoid their early degradation if the first stage is under control.

2.7 Materials in drug delivery systems

2.7.1 Ceramics for biomedical applications

Bioceramics have long been used as bone grafting for applications involving bone regeneration. Only the bioactive ceramics (such as hydroxyapatite, bioactive glass, and glass ceramics) and the resorbable ceramics (such as tricalcium phosphate and biocompatible glasses) are suitable for bone regeneration applications as scaffolds because they permit the adherence and proliferation of cells from the host tissue. This is true even though the class of ceramic biomaterials includes bioinert, bioactive, and resorbable ceramics [16].

2.7.2 Polymers in drug delivery systems

As previously indicated, DDS can be made utilizing synthetic or natural polymers that are either biodegradable or not (see Figure 2). Drugs, proteins, and cells can all be released using these polymeric systems. As mentioned in the preceding section, the polymers employed in DDS should exhibit a variety of characteristics that make them ideal materials to interact with the human body, with biodegradability being one of the most crucial characteristics.

Figure 2.

Overview of the polymers used in drug delivery systems [44].

Both swelling and osmosis can be used to manage solvent-activated systems. A hydrophilic polymeric crosslinked chain that can absorb a lot of water without dissolving is the foundation of systems that control swelling. The quantity of water that enters the polymeric matrix determines how quickly the medicine inside the system diffuses outward thanks to this water absorption (shown in Figure 3). Systems that are controlled by osmosis rely on a device.

Figure 3.

Drug release resulting from swelling of a polymeric matrix containing a DDS, without or with small amount of drug flows toward a chamber in which the drug is contained [17].

Numerous dissolved or degradable polymers are appropriate for use in medication delivery systems. The timing of the medication release or release outside the prepared material is managed in terms of the rate of water absorption and disintegration. The polymer’s high molecular weight and viscosity are blamed for the departure. Chitosan, sodium alginate, and zein protein are the three most well-known polymers utilized in this field.

2.7.3 Polysaccharides

Monosaccharide-repeating units are the building blocks of polysaccharides, which are high-molecular-weight compounds. They provide a wide variety of structures and attributes. The variety of possible uses is increased by reactive lateral groups, which allows for the changing of their structure. Dextran, alginate, and chitosan are a few of the materials that are typically used to make DDS.

A polysaccharide of bacterial origin, dextran is mostly made up of 1,6-linked D-glucopyranose units. It could have side branches at the positions α-1,2-, α-1,3-, or α-1,4 (Figure 4) [18].

Figure 4.

Molecular structure of dextran.

2.7.3.1 Chitosan

Chitosan, a cationic polymer created by the alkaline deacetylation of chitin, is the primary component of marine crab shells (see Figure 5). According to a review by Thu Ta and co-authors, chitosan-based hydrogels have been employed as DDS in the field of cancer therapy. There were many preparation techniques and crosslinking agents presented. Paclitaxel, doxorubicin, and camptothecin are a few examples of entrapped medicines [19].

Figure 5.

Schematic representation of the alkaline deacetylation of chitin to obtain chitosan.

2.8 Bioactive glass/polymer composites

Different material classes each have advantages and drawbacks of their own. For instance, bioactive glasses and other ceramic materials exhibit good biocompatibility, compression resistance, and corrosion resistance, but they have issues such as brittleness, low fracture strength, and high density. Polymers, on the other hand, may have a variety of forms, compositions, and physical characteristics, but they are too flexible and weak for some applications [20].

In this way, composite materials comprised of ceramic and polymers combine the benefits of each type of material while also addressing their drawbacks. In addition to modifying drug release patterns, polymers utilized in bioactive glass/polymer composites can enhance the mechanical and physical characteristics of bioactive glasses [6]. On the other hand, bioactive glass particles incorporated into polymers boost the material’s bioactivity while also improving mechanical performance [4]. The medication can be put in either the glass or the polymeric matrix in these devices. Drug loading in polymers is accomplished by incorporating medicines into a polymer matrix [21].

There are two ways that the medicine can be put into the glass particles (Figure 6): bioactive glass (BG) and bioactive glass with mesopores (MBG) [22].

Figure 6.

Schematic diagrams of: (a) drug incorporated during sol-gel syntheses of BG; (b) drug entrapped inside porous of bioactive glass; (c) drug bonded by H bond on surface of BG; and (d) drug bonded by H bond on inner surface of mesoporous BG.

Different morphologies, such as the dispersion of bioactive glass particles into a polymeric matrix or polymeric fibers, the coating of a polymer on the surface of a bioactive glass scaffold, or the coating of bioactive glass particles on the surface of a polymeric scaffold, can result in the association of polymers with bioactive glass. Each system has distinct mechanical traits and capabilities and may be used for specialized tasks (Figure 7).

Figure 7.

Schematic diagrams of: (a) bioactive glass particles in a polymeric matrix; (b) bioactive glass particles in polymeric fibers; (c) coating of a bioactive glass scaffold with polymer; and (d) coating of a polymeric scaffold with bioactive glasses particles.

2.9 Clinical applications of bioactive glass/polymer for DDS

Utilizing bioactive glass/polymer composites, various medications may be locally released. Drug delivery systems have employed a variety of medications, including anti-inflammatory, osteogenic, anticancer, and antibiotics. This section will discuss various uses for these medications put into glass or polymer matrixes (seen in Figure 8) [23].

Figure 8.

Exemplifies functionalized pore wall of mesoporous.

2.10 Antibiotics in DDS

Since the use of biomaterials like bone fillers, bone substitutes, or orthopedic implants may have unfavorable outcomes like infections, antibiotics make up the majority of the medications used in local release. Because the osteogenic response of glass and the drug release by the composite may be combined, employing glass/polymer scaffolds is preferable to using glass and polymers separately. Additionally, substantial medication dosages can be locally released, improving the treatment’s specificity. This capacity is necessary for bone infections like osteomyelitis because it enables the diffusion of high dosages of antibiotics to avascular regions that the systemic administration cannot [24]. Numerous studies have suggested various bioactive glass/polymer scaffolds for releasing antibiotics.

2.11 Anti-inflammatory in DDS

Inflammatory reactions are frequently seen following surgery or implant procedures. Anti-inflammatory medicine local release may be a solution to reduce this issue.

Anti-inflammatory responses are crucial for tissue regeneration because they aid in the removal of foreign infections, but if they are too strong, they can harm the tissue.

2.12 DDS used to cancer treatment

Bone cancer is another issue that causes a reduction in bone mass. Chemotherapy, which involves administering one or more medications systemically to cancer cells, is a common treatment for bone cancer. Chemotherapy has a drawback: Side effects can harm patients’ quality of life and have an overall unfavorable impact on their bodies. For the treatment of bone cancer, local medication administration may enhance the medicine’s activity against cancer cells and minimize or eliminate adverse effects. The interaction with bioactive eyewear may potentially promote the repair of damaged tissue (Figure 9).

Figure 9.

Schematic diagram showing the therapeutic fiber scaffolds incorporating nanospheres of mesoporous bioactive glass with dexamethasone (Dexa-loaded mBGn), where the drug releasing effect and bioactivity of mBGn can be synergized to regulate osteogenic responses.

Recombinant granulocyte colony-stimulating factor treatment showed a diminished impact, while recombinant granulocyte-macrophage colony-stimulating factor had no encouraging impact. Recombinant granulocyte-macrophage colony-stimulating factor, on the other hand, increased acute myeloid leukemia incidence (by 75%), while colony-stimulating factor 1 and recombinant granulocyte colony stimulating factor had no effect. This was discovered when different factors were administered several months after the leukemogenic treatment. Recombinant interleukin 6 treatment, on the other hand, significantly (23%) decreased the risk of acute myeloid leukemia. The results show that radiation-induced preleukemia, a component of radiation-induced acute myeloid leukemia in mice, is a multiphase process [25].

2.13 Multifunctional drug delivery systems

In addition to coatings, in more sophisticated systems, such medication delivery systems have also been created: synthetic macro- and mesoporous silica Santa Barbara Amorphous (SBA-15) with magnetic particle-filled porous bioactive glass (magnetic SBA-15). After being submerged in a hexane/ibuprofen solution to load the anti-inflammatory medication ibuprofen, magnetic SBA-15 was coated with polymer (lactic-co-glycolic acid). The diabetic medication metformin HCl was then added to bioactive glasses. In vitro testing revealed the release characteristics of both medications [26].

2.14 Why glucocorticoids in DDS

Drugs called glucocorticoids, sometimes known as corticosteroids or “steroids,” are particularly efficient in reducing inflammation brought on by ailments such as asthma and arthritis. They may also be administered to replace the body’s own natural steroids in cases of pituitary or adrenal illness. Prednisolone and dexamethasone are the two glucocorticoids that are most often utilized. They typically play a crucial role in the management of numerous medical problems and have the potential to save lives. However, doctors often utilize the lowest amount necessary to manage the disease and only suggest them when it is truly essential.

2.15 How do they affect bone?

One of the known adverse effects of glucocorticoid therapy is that it might weaken bones and increase the likelihood of fractures, especially when used for an extended length of time. Both direct and indirect actions of glucocorticoids on bone contribute to bone loss and decreased bone strength.

By promoting the activity of natural bone removal cells and decreasing the activity of bone-building cells, they have a detrimental effect on bone directly. They may also impact the amounts of sex hormones and the way the body processes calcium. The degree of bone loss varies from person to person, but for individuals taking 7.5 mg or more of prednisolone per day, the risk of fractures rises by more than 50% in the first year of treatment.

2.16 Do all glucocorticoid treatments affect bone?

The dosage of glucocorticoids and how they are administered both affect how they affect bones throughout treatment (as an injection, cream, inhaler). But glucocorticoid medications are the ones that have been most closely linked to bone loss. Although studies indicate that increased fracture risk can occur even with modest doses of prednisolone (2.5–7.5 mg per day) and climb further with increasing daily dosages, the precise quantity that is damaging to bone varies depending on the individual. Another important factor is how long glucocorticoid pills are taken. The majority of specialists concur that there may be an effect on bone if they are used constantly in tablet form for longer than 3 months. If extremely large dosages are utilized, this impact can be seen much sooner. The overall health advantages of glucocorticoids far outweigh any potential slight negative effect on bones when they are used in low doses to replace what the body is unable to produce (e.g., in Addison’s disease or pituitary disease), so it is crucial that they are taken as prescribed by your doctor [27].

2.17 Dexamethasone (Dexa)

Additional medications may be given either before or simultaneously with the chemotherapeutic medicines to lessen or eliminate these chemotherapy resistance factors. These medications may or may not have therapeutic benefits on their own, but their main function is as adjuvants, enhancing the effectiveness and/or reducing the toxicity of chemotherapeutic medicines. Dexa (Figure 10) is one such medication. Synthetic glucocorticoids like Dexa are well known for their ability to reduce inflammation and suppress the immune system. It has demonstrated benefit against several malignancies, including leukemia, and has been widely used as an anti-emetic in combination with chemotherapy drugs [28].

Figure 10.

Structures of dexamethasone.

However, recent preclinical and clinical studies have concentrated on its use as a chemotherapeutic adjuvant. According to studies, pretreatment with Dexa can lessen the toxicity and, in some situations, boost the effectiveness of chemotherapy drugs. Prednisolone and Dexa, for instance, both efficiently defended progenitor cells in four strains of mice against 5-fluorouracil, a chemotherapeutic drug that is specific to the cell cycle and is antimetabolic. Blood cell counts and the number of bone marrow progenitors both returned to normal after 3–5 days and 1–2 days, respectively, of not receiving glucocorticoids. With Dexa, the same degree of effectiveness may be attained at almost 16.5 times the dosage of prednisolone.

In six xenograft models studied (2 colon, 2 breast, 1 lung, and 1 glioma tumors), Wang et al. found that pre-administration of Dexa was able to greatly boost the effectiveness of carboplatin, a DNA alkylating agent; gemcitabine, an antimetabolite; or a combination of both medicines by 2–4-fold. The same team also looked at how Dexa affected the treatment with Adriamycin, an anthracycline antibiotic that may intercalate DNA and is also known as doxorubicin, with similar outcomes. In a syngeneic model of breast cancer, pre-administration of Dexa led to an almost total suppression of tumor development. Dexa pretreatment has been shown in clinical studies to decrease hematological toxicity and speed up the recovery of absolute granulocyte count and platelet count [29].

By employing normal phase LC with quaternary mobile phase with regulated water content, UV detection at 254 nm, and cortisone as an internal standard, dexamethasone content in drug substance and elixir may be found. In bulk drug material and elixir, TLC, IR spectroscopy, and relative LC retention time ratios are used to validate identification.

2.18 Dexamethasone interactions

Dexamethasone’s role in treating rats with gastrointestinal constipation brought on by morphine, verapamil, and atropine has been investigated. Dexamethasone was able to counteract the dose-related inhibition of charcoal meal transit brought on by these medications. More effectively than altering the effects of verapamil, dexamethasone reversed the constipation caused by morphine and atropine. Dexamethasone’s interaction with its receptor was shown to have the potential to release a greater amount of acetylcholine, which would reverse the constipation caused by atropine or morphine. Dexamethasone’s little impact on verapamil-induced constipation revealed that calcium influx was not as important as previously thought. The aforementioned findings point to the significance of steroids in gastrointestinal transit and offer a potential mechanism by which dexamethasone might alleviate constipation brought on by morphine and atropine [30].

2.19 Dexamethasone health hazard

SYMPTOMS Fluid and electrolyte disturbances, pituitary-adrenal suppression, hyperglycemia, increased susceptibility to infection, including tuberculosis, myopathy, growth arrest, hypokalemic alkalosis, and Cushing’s syndrome, which includes “moon-face,” “buffalo-hump,” striae, acne, and hirsutism, are all symptoms of exposure to this type of compound. Ecchymoses, “central obesity,” and enlarged supraclavicular fat pads are some additional signs of Cushing’s syndrome.

This condition can also lead to increased bruising and flushing. Behavioral abnormalities, glycosuria, anxiousness, mood or psyche changes, psychopathy’s of the manic-depressive or schizophrenia type, and suicidal thoughts are further signs of exposure. Candidiasis, gluconeogenesis, heart failure (in severe cases), spontaneous fractures, increased hunger, slower wound healing, hyperhidrosis, neurological and mental problems, intracranial hypertension, and increased blood coagulability are all possible side effects of exposure. Aseptic necrosis of the bone, amenorrhea, muscle weakness, salt and water retention, hypertension, edema, increased severity of diabetes, pancreatitis, thrombotic episodes, and osteoporosis are other possible side effects. Sleeplessness, skin eruptions, depression, euphoria, decreased pain perception, weakness, deafness, convulsions, intestinal perforation in ulcerative colitis, hypokalemia, muscle deterioration, Achilles tendon rupture, pseudotumor cerebri, and cardiac conduction defect are additional signs of exposure to this type of substance.

Congestive heart failure, immune system suppression, impaired glucose tolerance, habituation, and the emergence of hidden psychological disorders are among its potential side effects. Additionally, it may result in potassium loss, muscle mass loss, vertebral compression fractures, abdominal distention, ulcerative esophagitis, thin and fragile skin, petechiae, erythema, increased sweating, suppressed skin test reactions, allergic dermatitis, urticaria, angioneurotic edema, vertigo, headache, decreased carbohydrate tolerance, exophthalmos, hypersensitivity, thromboembolism, malnutrition. Ascites may occur. Subcutaneous atrophy and skin collagen loss might result from skin exposure to this kind of substance. Burning, secondary infections, itching, irritation, pigmentation, dryness, folliculitis, and hypertrichosis are additional signs of this approach. This kind of chemical can cause cataracts, increased intraocular pressure, corneal ulcers, and impaired vision in the eyes. Glaucoma might also happen [31].

2.20 Acute/chronic hazards

Through consumption, inhalation, or skin absorption, this substance may be dangerous. It could irritate others. It could result in lacrimation. It releases deadly fumes of carbon monoxide, carbon dioxide, and hydrogen fluoride when heated to the point of disintegration [32, 33].

2.21 Dexamethasone chemical dangers

When heated over 275°C, it decomposes. This releases harmful gases. This creates a risk of fire and explosion, and reacts with carbon disulfide, copper, lead, silver, mercury, and other metals. Particularly shock-sensitive chemicals are created as a result and with acids reacts. As a result, poisonous and explosive hydrogen aside is produced, with a melting point between 504 and 507 degrees F. [25, 34].

2.22 Preparation of drug-loaded SLNs

It has been demonstrated that using Dexa-P improves medication loading in solid lipid nanoparticles (SLNs). This section’s objectives were to manufacture and describe SLNs that were loaded with Dexa-P and to compare them to other medications with a comparable structure or lipophilicity. Size, form, structure, and crystallinity of SLNs will be evaluated, in addition to the previously mentioned characteristics (drug loading and encapsulation effectiveness). The free and encapsulated medication will be separated using ultrafiltration, and the amount will be measured using an HPLC-UV test. For the comparative experiments, curcumin and ascorbic palmitate (AP) will be employed. The palmitate moiety that may link with the SLN lipids is absent from curcumin, despite the fact that both medicines are lipophilic.

2.23 Stability of drug-loaded SLNs

The presence of CE activity seems to be necessary for the release of dexa from the SLNs. This section’s objectives were to 1) establish the stability of SLNs and 2) demonstrate dexa-P retention with the SLNs in circumstances similar to those in human plasma (specifically the absence of CE activity). Monitoring the growth and morphology of SLNs cultured at 37°C was the main goal of the early experiments. The influence of SLN concentration on particle size growth was assessed, and SLNs returned to 4°C after incubation at 37°C were tested for size recovery to better clarify the process of particle size growth. After that, SLNs were exposed to human serum albumin (HSA), and a representative protein, and size and turbidity alterations were observed. As a backup strategy, size exclusion chromatography (SEC) was applied to validate the SLNs’ intact status in the presence of HSA. A multi-step filtration procedure that involved first filtering via a 0.2-μm membrane and then ultrafiltration was used to ascertain the retention of Dexa-P with the SLNs in the presence of human plasma. Calculating the quantity of medication retained with the SLNs involved taking into consideration the known protein binding.

2.24 Storage stability of drug-loaded SLNs

This section’s objectives were to examine the long-term stability of aqueous and lyophilized SLNs and to optimize a process for lyophilizing SLNs. The following factors were taken into account for optimizing the lyophilization protocol: lyoprotectant (LP) type and concentration, SLN concentration, freezing temperature, freezing rate, and drying time. The particle size, shape, mono dispersity, and drug loading of SLNs were evaluated. Lyophilized SLNs and SLN suspensions were kept at 4°C and 25°C/60% RH for the long-term stability testing. At days 0, 1, 3, 7, 14, and months 1, 2, and 3, samples were taken to evaluate the size of the particles and drug loading [35].

2.25 Biological activity

It is permitted to use dexamethasone to lessen immunological response and minimize inflammation. The following cancers are treated with it in combination with other medications: leukemia, lymphoma, fungus mycoides (a type of cutaneous T-cell lymphoma). The following cancer-related diseases are also prevented or treated using dexamethasone alone or in combination with other medications: anemia, cerebral edema (fluid build-up in the brain) (fluid build-up in the brain), hypersensitivity to drugs (allergic reactions), hypercalcemia (high blood levels of calcium) (high blood levels of calcium), thrombocytopenia (low platelet levels) (low platelet levels). Many different illnesses and ailments are treated with dexamethasone either on its own or in combination with other medications. The medication is still being researched for the treatment of many cancers and other illnesses [36].

2.26 Therapeutic uses

Dexamethasone is mostly utilized as an immunosuppressant or anti-inflammatory drug. The medication is insufficient by itself to treat adrenocortical insufficiency because it only possesses limited mineralocorticoid characteristics. Dexamethasone must be administered in conjunction with a mineralocorticoid to effectively treat this disease: steroidal anti-inflammatory drugs, antiemetics, hormonal antineoplastics, synthetic and topical glucocorticoids, and antihistamine [37].

In babies and children with Haemophiles influenzae meningitis, there is some evidence that short-term supplementary treatment with IV dexamethasone may reduce the incidence of audiologic and/or neurologic sequelae. Patients with Streptococcus pneumoniae meningitis may also benefit. The American Academy of Pediatrics (AAP) and other medical professionals advise considering adjunctive dexamethasone therapy in infants and kids older than 6 weeks with known or suspected bacterial meningitis, particularly in those with suspected or confirmed Haemophilus influenzae infection, during the first 2–4 days of anti-infective therapy. Dexamethasone should be started before or concurrently with the initial dosage of an anti-infective medication if it is used [38].

3. In vitro bioactive analysis

3.1 Standard operating procedure for (SBF) preparation

Kokubo’s [39] Simulated body fluid (SBF) is a metastable solution made up of supersaturated calcium and phosphate ions in relation to apatite.

As a result, (SBF) is ready as follows:

• The buffer solution with pH values between 4 and 7 was used to calibrate the pH meter.

• The procedure is conducted with the temperature at 37.4°C.

• SBF solution was created by combining the listed components in the right amounts and sequence (as specified in Table 2) in 950 ml of distilled water.

• Until order number (8), the chemicals (Table 2) were added to the distilled water one at a time, after the full dissolution of each reagent.

• To prevent a local pH rise in the solution, the addition of reagent (9) should be done gradually and with less than 1gm.

• Following the addition of order number (9), the solution’s temperature is examined, and pH is determined with the temperature at 37.4°C.

• The pH of the solution should be roughly identical at this value (7.5).

• To set the pH at 7.4, an HCl solution was titrated using a pipette.

• Following pH correction, 50 ml of distilled water was added to the solution, bringing its total volume to 1000 ml.

• Rinse a 1000 ml polyethylene (or polystyrene) container at least three times with a small amount of the prepared solution (SBF).

• Transfer the solution to the plastic bottle from the flask.

• The bottle was kept in a 5–10°C refrigerator.

Order	Reagent	Amount (g/L)	Formula weight
1	Tris	6.057	121.1356
2	HCl	39 (ml)	—
3	NaCl	8.006	58.44277
4	NaHCO3	0.352	84.00687
5	KCl	0.223	74.551
6	K2HPO4.3H2O	0.228	228.222
7	CaCl2	0.277	110.986
8	Na2SO4	0.071	142.03714
9	MgCl2.6H2O	0.304	203.3034

Table 2.

Reagents for preparation of simulated body fluid (SBF).

3.2 The soaking of the samples in (SBF)

By soaking in 50 ml of Kokubo’s (SBF), (Figure 11), the in vitro bioactivity of bioglass (BG), bioglass/chitosan (BG/CH), and different ratios of BG/CH dexamethasone was examined. The SBF solution has a buffered pH of (7.4) [40].

Figure 11.

Test of the static SBF in a plastic container at 37°C.

The samples in plastic containers were kept at a constant temperature of 37°C for 33 days in a thermodynamic (shaking-water bath) (see Figure 12).

Figure 12.

Thermodynamic incubator (water bath).

The specimens were taken out of the solution, cleaned with distilled water, and then allowed to dry at room temperature after 33 days of immersion.

3.3 Elemental analysis: UV spectrophotometer technique

Each test tube had a 2 ml sample of SBF removed from it 1, 2, 4, 8, 16, 21, and 33 days after the immersion started.

And kept frozen until they were evaluated using UV-Vis spectroscopy (JASCO v-630) (see Figure 13) to determine the concentration of Ca, P, and dexamethasone released when a medication concentration increased over time [41].

Figure 13.

UV-visible spectroscopy JASCO v-630.

4. Determination of drug release

4.1 Determination of the characteristic absorption peaks

The UV-visible (VIS) absorption spectra of Dexa solution are displayed in Figure 14. Dexa have absorption peaks were found to be strongest at wavelengths of 237, 240, and 242 nm, respectively. The absorption spectra for dexamethasone solution were photographed at 240 nm in wavelength [42].

Figure 14.

UV-visible absorption spectra of dexamethasone concentration.

4.2 Calibration curve of the release drug dexamethasone

Utilizing several drug reference solutions in descending order at the maximum wavelength (λ) at 240 nm, which corresponds to Dexa medicines, the UV-VIS absorption spectroscopy equipment was calibrated.

Stock solution was divided into aliquots (50, 25, 12.5, and 6.75 ml) and combined with (2 ml) of distilled water at a pH of 7.4 to create concentrations ranging from 25 to 200 g/ml. Using a UV-VIS spectrophotometer, the absorbance of these solutions was evaluated at 240 nm, as indicated in Table 3 [43].

no	Amount(μl)	Concentration(μg/ml)	Absorbance (%)
1	50	200	2.2532
2	25	100	1.7689
3	12.5	50	0.9557
4	6.75	25	0.4836

Table 3.

Standard absorption values of dexamethasone in distilled water pH 7.4 with different concentration.

The drug calibration curve was altered to suit a straight line with a correlation coefficient (R²) of 0.93692 Dexa, as shown in Figure 15.

Figure 15.

Calibration curve of the release drug dexamethasone.

4.3 Determination of the amount of drug released

The dynamic in vitro release is depicted in Figure 16. Dexamethasone absorption peaks were seen in all samples individually from zero day soaking in SBF to 33 days.

Figure 16.

Dexamethasone absorbance (%) at 240 λ during (1–33) days of soaking.

UV-visible absorption spectroscopy was used to identify the absorbance peaks intensities of the drug samples across the preset time periods. The equivalent quantity of the drug was calculated using the relevant calibration curve and is shown in Table 4 as the percentage of dexamethasone drug release.

Sample Time	BG/CH5D		BG/CH10D		BG/CH15D		BG15D
	μl	%	μl	%	μl	%	μl	%
1 day	21.05	7.73	30.77	10.88	28.57	10.24	31.64	10.85
2 days	29.50	18.58	31.80	22.14	33.93	22.40	47.87	27.279
4 days	46.41	35.63	47.32	38.88	40.55	36.93	44.01	42.37
8 days	48.00	53.28	46.45	55.32	44.47	52.87	42.11	56.82
16 days	46.61	70.41	45.64	71.47	45.64	69.22	42.16	71.28
21 days	46.41	87.46	47.94	88.44	47.09	86.10	43.33	86.15
33 days	34.09	100	32.66	100	38.77	100	40.36	100
Total amount	272.121		282.622		279.0668		291.5054
P-value	0.01		0.01		0.01		0.01

Table 4.

The percentage of dexamethasone drug released from composite samples.

Table 4 shows all the percentages of dexamethasone released from all samples BG/CH5D BG/CH10D BG/CH15D BG15D and over the different periods after 1, 2, 4, 8, 16, 21 and 33 days, and it also shows the release rate of each quantity of the used drug "Dexamethasone" for each sample over the same period as previously described.

The dexamethasone release profile revealed a lower initial release that was initially sluggish and subsequently increased. After 96 hours (4 days), the rate of Dexa release rose briefly before returning to normal (Figure 17).

Figure 17.

The amount of release Dexa concentration from samples for (1–33) days.

The drug’s release profile was evaluated in three stages: an initial burst release (stage I), continuous release (stage II), and declining release (stage III) (stage III).

The quantity of medication released from BG15D, BG/CH5D, BG/CH10D, and BG/CH15D composites reduced after 21 days. The profile is generally comparable for the three concentrations BG/CH5D, BG/CH10D, and BG/CH15D, as predicted given the bioglass/chitosan composites that support the medication.

The drug release is regulated by two factors: diffusion and polymer breakdown. According to the release profiles, the mechanism of Dexa release appears to be through polymer breakdown rather than diffusion owing to chemical interaction amino groups of chitosan and carbonyl groups of Dexa [44].

4.4 Accumulative release of Dexa

The experimental findings showed that dexamethasone was released faster from bioglass (BG15D) than from bioglass/chitosan composites (BG/CH15D). This is owing to the fact that drug release from bioglass (BG15D) can only be impacted by diffusion, but drug release from BG/CH5D, BG/CH10D, and BG/CH15D may be sustained by chitosan degradation based on the chemical interaction of chitosan amino groups and dexamethasone carbonyl groups (Figure 18).

Figure 18.

Release profile of dexamethasone in terms of the percentage (%) of dexamethasone released as a function of time.

5. Conclusion

At various dilution ratios, the controlled release was tested using “JASCO v-630” UV visible spectroscopy. A standard curve was developed to establish a link between the absorption rate, as measured by the UV device, and the drug concentration in the medium utilized (SBF). The release profile reveals that the dexamethasone release may be sustained for more than 30 days, and the drug release experimental data indicate that the release is driven by chitosan polymer breakdown. Based on the findings of this study, we can conclude that (bioglass/chitosan) is a good function material as a carrier for anti-inflammatory dexamethasone drug as a corticosteroid and that it may be successfully employed in bone tissue engineering applications.

It has been determined that the release profile showed that the dexamethasone release may be sustained for more than 30 days, and the drug release experimental data indicate that the release is driven by chitosan polymer breakdown. Based on the findings of this investigation, we therefore proposed that bioglass/chitosan is a suitable functional material as a carrier for the anti-inflammatory medication dexamethasone in this study.

Acknowledgments

I first and foremost thank the All-Powerful Allah for both my possessions and lack of possessions. He is the ruler of the universe. Salutations to Muhammad (PBUH), the finest and most excellent of all beings. Among the academics I am grateful to and indebted to are my brother Dr. Ahmed Ali Abdel-Aal Mohamed, my best friend Dr. Abd elrahmaan Al-esnawy, and my teachers Dr. Ahmed S. Abd raboh, Prof. Dr. M. Y. Hassan, and Prof. Dr. Khairy M. T. Ereiba of the Faculty of Science at Al-Azhar University.

Conflict of interest

Not applicable.