Current Drug Delivery - Volume 18, Issue 5, 2021

Osteomyelitis is a bone marrow infection which generally involves cortical plates and which may occur after bone trauma, orthopedic/maxillofacial surgery or after vascular insufficiency episodes. It mostly affects people from the Third World Countries, the elderly and patients affected by systemic diseases e.g. autoimmune disorders, AIDS, osteoporosis and microvascular disease. The highest percentage of osteomyelitis cases (almost 75%) is caused by Staphylococcus spp., and in particular by Staphylococcus aureus (more than 50%). The ideal classification and the diagnosis of osteomyelitis are two important tools which help the physicians to choose the best therapeutic strategies. Currently, common therapies provide an extensive debridement in association with intravenous administration of antibiotics (penicillin or clindamycin, vancomycin and fluoroquinolones among all for resistant microorganisms), to avoid the formation of sequestra. However, conventional therapeutic approach involves several drawbacks like low concentration of antibiotics in the infected site, leading to resistance and adverse effects due to the intravenous administration. For these reasons, in the last years several studies have been focused on the development of drug delivery systems such as cements, beads, scaffolds and ceramics made of hydroxyapatite (HA), calcium phosphate (CaP) and β-tricalcium phosphate (β-TCP) which demonstrated to be biocompatible, poorly toxic and capable to allow osteointegration and a prolonged drug release. The aim of this review is to provide a focus on current therapies and latest developed drug delivery systems with particular attention on those based on CaP and its derivatives, hoping that this work could allow further direction in the field of osteomyelitis.

The current COVID-19 pandemic has provoked the urgent requirement to search for effective treatments since the implications are so huge globally as compared to the earlier pandemics. Momentarily, there has been no effective medicine for SARS-CoV-2 infection, and supportive care tends to be the most effective approach to treat COVID-19 patients. The rapidly growing awareness of SARS-CoV-2 virology offers a large number of possible drug targets. The World Health Organisation (WHO) is steadily updating the treatment protocol for COVID-19 based on the recent clinical trials. In the present review, we have summarised the possible mode of action, clinical evidence, consequences of dexamethasone as the therapeutic agent against Covid-19. Currently, many corticosteroids are being tested in ongoing randomised trials. Dexamethasone could come as the life-saving drug. Dexamethasone drug looks useful only in those patients who are already in a critical state. We might allow dexamethasone as a fascinating shot, if the drug proves to be clinically favourable for long-term health effects of Covid-19 recovered patients. It is commonly accepted to reinforce approved drugs in the fight against newly emerging diseases such as COVID-19 as these drugs have established pharmacokinetic profiles and protection. The current focus should be on the development of novel proven therapeutics along with vaccines. There is a need for high quality, more extensive, rapid and collaborative randomized controlled trials with more control groups.

Skin, the most significant protective organ in the body, may face serious problems, including cancer, infectious diseases, etc., requiring different drugs for the treatment. However, most of these drugs have poor chemical and physical stability, and insufficient penetration through the skin layers. In recent years, with the development of nanotechnology, it has been possible to load a variety of drugs into nanocarriers, to effectively targeted drug delivery. The unique structure of niosome presents an effective novel drug delivery system with the ability to load both hydrophilic and lipophilic drugs, having many potential therapeutic applications including skin treatment. However, surveying and discussing these recent, rapidly growing reported studies, along with their theoretical principals, are required for the full understanding and exploring the great potential of this approach in skin diseases and cosmetic treatments. To this aim, an emphasis has been given to the factors affecting the penetration of niosome into the skin and their laboratory measurements and dependency on the niosome composition. In sum, longer tail surfactants for storing hydrophobic drugs and intracellular passing and surfactants with a large head group for penetrating hydrophilic drugs are more suitable. Cholesterol and oleic acid are commonly used lipids to gain more stability and permeability, respectively. The ionic component in the niosome interrupts cellular connectivity, thus making it more permeable, but it may cause relative cell toxicity. Herbal oils have been used in the structure to make the nanoparticles elastic and allow them to pass through pores without changing the size of the particles.

Transdermal drug delivery helps to circumvent the first-pass effect of drugs and to avoid drug-induced gastrointestinal tract irritation, compared with oral administration. With the extensive application of ethosomes in transdermal delivery, the shortages of them have been noticed continuously. Due to the high concentration of volatile ethanol in ethosomes, there are problems of drug leakage, system instability, and ethosome-induced skin irritation. Thus, there is a growing interest in the development of new generations of ethosomal systems. Functionalized ethosomes have the advantages of increased stability, improved transdermal performances, an extended prolonged drug release profile and site-specific delivery, due to their functional materials. To comprehensively understand this novel carrier, this review summarizes the properties of functionalized ethosomes, their mechanism through the skin and their modifications with different materials, validating their potential as promising transdermal drug delivery carriers. Although functionalized ethosomes have presented a greater role for enhanced topical delivery, challenges regarding their design and future perspectives are also discussed.

In response to the global outbreak caused by SARS-CoV-2, this article aims to propose the development of nanosystems for the delivery of hydroxychloroquine in the respiratory system to the treatment of COVID-19. A descriptive literature review was conducted, using the descriptors “COVID-19”, “Nanotechnology”, “Respiratory Syndrome” and “Hydroxychloroquine”, in the PubMed, ScienceDirect and SciElo databases. After analyzing the articles according to the inclusion and exclusion criteria, they were divided into 3 sessions: Coronavirus: definitions, classifications and epidemiology, pharmacological aspects of hydroxychloroquine and pharmaceutical nanotechnology in targeting of drugs. We used 131 articles published until July 18, 2020. Hydroxychloroquine seems to promote a reduction in viral load, in vivo studies, preventing the entry of SARS-CoV-2 into lung cells, and the safety of its administration is questioned due to the toxic effects that it can develop, such as retinopathy, hypoglycemia and even cardiotoxicity. Nanosystems for the delivery of drugs in the respiratory system may be a viable alternative for the administration of hydroxychloroquine, which may enhance the therapeutic effect of the drug with a consequent decrease in its toxicity, providing greater safety for implementation in the clinic in the treatment of COVID-19.

Aim: To develop a co-crytsal of Telmisartan for enhancing its solubility in water. Background: Intermolecular interaction happens in crystal packing; it utilizes and helps to understand the design of new solid with their respective chemical and physical properties called crystal engineering. It is a blueprint of molecular solids with specific chemical and physical properties through an understanding and handling of intermolecular interaction for increasing the solubility, in case of poor water-soluble drugs. Objectives: The study was taken under consideration with an aim to generate and synthesize a cocrystal form of Telmisartan (TEL) with L-lysine to improve its water solubility, dissolution, and micrometric properties. Methods: Using dry grinding technique, solvent evaporation and cooling crystallization, the results revealed a generation of co-crystals with enhanced solubility by liquid drop grinding method. Hence, this process was further explored to investigate various formulations and process parameters that could significantly affect the crystal solubility, dissolution, and micrometric properties. Results: The solubility of TEL co-crystals was enhanced by L-lysine. Further, the optimized batch was subjected to its micrometric evaluation and physiochemical characterization like FT-IR, NMR, PXRD. The result of the micrometric evaluation showed better results as compared to standards. The dissolution studies also showed a better dissolution rate for TEL co-crystal tablets than TEL tablets formulation. Conclusion: Co-crystals of TEL with L-lysine showed better solubility and dissolution rate.

Aim: The aim of the study was to formulate, characterize, and evaluate the Resveratrol- loaded Cubosomes (RC) for topical application. Background: Resveratrol (RV) is a nutraceutical compound with exciting pharmacological potential in different diseases, including cancers. Many studies on resveratrol have been reported for anti- melanoma activity. Due to its low bioavailability, the therapeutic activities of resveratrol are strongly limited. Hence, an approach with nanotechnology has been made to increase its activity through transdermal drug delivery. Objective: To formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC). To evaluate Resveratrol-loaded Cubosomal Gel (RC-Gel) for its topical application. Methods: RC was formulated by homogenization technique and optimized using a 2-factor 3-level factorial design. Formulated RCs were characterized for particle size, zeta potential, and entrapment efficiency. Optimized RC was evaluated for in vitro release and stability study. Optimized RC was further formulated into cubosomal gel (RC-Gel) using carbopol and evaluated for drug permeation and deposition. Furthermore, developed RC-Gel was evaluated for its topical application using skin irritancy, toxicity, and in vivo local bioavailability studies. Results: The optimized RC indicated cubic-shaped structure with mean particle size, entrapment efficiency, and zeta potential were 113±2.36 nm, 85.07 ± 0.91%, and -27.40 ± 1.40 mV, respectively. In vitro drug release of optimized RC demonstrated biphasic drug release with the diffusion-controlled release of resveratrol (RV) (87.20 ± 3.91%). The RC-Gel demonstrated better drug permeation and deposition in mice skin layers. The composition of RC-Gel has been proved non-irritant to mice skin. In vivo local bioavailability study depicted the good potential of RC-Gel for skin localization. Conclusion: The RC nanoformulation proposes a promising drug delivery system for melanoma treatment simply through topical application.

Objective: The current study aimed to investigate the potential of Solid Self-Emulsifying Drug Delivery Systems (solid SEDDS) loaded with Testosterone Undecanoate (TU) (solid TUSEDDS). The solid TU-SEDDS was composed of TU, Medium-Chain Triglycerides (MCT, oil), 2- Chloro-1-(chloromethyl) ethyl carbamate (EL-35, surfactant) and polyethylene glycol (PEG400, cosurfactant). It was expected to improve the dissolution and oral bioavailability of TU, as a result of investigating the feasibility of the clinical application of SEDDS. Methods: First, a TU-SEDDS was developed by using rational blends of components with the good solubilizing ability for TU. Next, a ternary phase diagram was constructed to determine the self-emulsifying region, and the formulation was optimized. Then, the solid TU-SEDDS formulation was established by screening suitable solid adsorptions. Finally, the prepared SEDDS, TUSEDDS and solid TU-SEDDS formulations were evaluated in vitro and in vivo. Results: The size of the solid TU-SEDDS was 189.1 ± 0.23 nm. The Transmission Electron Microscopy (TEM) results showed that the oil droplets were homogenous and spherical with good integrity. The Differential Scanning Calorimetry (DSC) and X-Ray Powder Dffraction (XRD) results indicated that the solid TU-SEDDS formulation almost preserves the amorphous state. Scanning Electron Microscopy (SEM) indicated that neusilin US2 successfully adsorbed the TU-SEDDS. Drug release indicated that the dissolution of the solid TU-SEDDS was faster than that of Andriol Testocaps ®. Furthermore, in vivo pharmacokinetic (PK) studies in Sprague-Dawley (SD) rats showed that the Area Under the Curve (AUC) of the solid TU-SEDDS (487.54±208.80 μg/L×h) was higher than that of Andriol Testocaps® (418.93±273.52 μg/L×h, P < 0.05). In beagles not fed a high-fat diet, the AUC of the solid TU-SEDDS (5.81±4.03 μg/L×h) was higher than that of Andriol Testocaps ® (5.53±3.43 μg/L×h, P > 0.05). In beagles fed a high-fat diet, the AUC of the solid TUSEDDS (38.18±21.90 μg/L×h) was higher than that of Andriol Testocaps® (37.17±13.79 μg/L×h, P > 0.05). Conclusion: According to the results of this research, oral solid TU-SEDDS is expected to be another alternative delivery system for the late-onset hypogonadism. This is beneficial to the transformation of existing drug delivery systems into preclinical and clinical studies.

Objective: Madhuca longifolia has been used for the treatment of renal cancer. Therefore, the current study describes the protective effects of biofabricated silver nanoparticles (MLAg- NPs) using Madhuca longifolia aqueous leaves extract against diethylnitrosamine (DEN) induced Renal Cell Carcinoma (RCC) in rats. Methods: Animals were categorized into five groups and treated with doses of silver nanoparticles for 16 weeks. Antineoplastic effect in renal cancer was dose dependent to control the macroscopical variations when compared to DEN induced group. Significant changes were observed in biochemical parameters and dose graded improvement in the level of antioxidants parameters were accountable for its protective nature. Results: Silver nanoparticles in dose dependent manner was effective to modify the raised levels of pro-inflammatory cytokines and inflammatory mediators during renal cancer. Alteration in renal histopathology were also detected in the silver nanoparticles treated group, which show its safety concern. Biofabricated silver nanoparticles (MLAgNPs) using Madhuca longifolia can convey significant chemo-protective effect against renal cancer by suppressing the IL-6, TNF-α and IL-1β by nuclear factor-kappa B (NF-ΚB) pathway. Conclusion: Our outcomes implicates that biofabricated MLAgNPs exhibited a chemoprotective potential in the prevention and intervention of RCC.

Background: In this work the cytotoxicity and gastric and gastrointestinal resistance of a high-load synthetic expandable mica, Na-mica-4, is studied for the first time. The hydrophilic character of this clay mineral can be modified by ion exchange reaction between Na+ inorganic cations housed in the interlayer space, and surfactant molecules, resulting in the formation of an organophilic material. This adsorption capability of organic compounds makes them very useful for a wide range of applications, such as their use as drug carriers. Previous studies have shown the high adsorption capacity of organofunctionalized Na-mica-4 of different types of drugs. Objetive: To carry out initial trials aimed at testing the cytotoxicity of a synthetic organofunctional expandable mica and evaluating its resistance to gastric and gastrointestinal digestion. Methods: A highly charged sodium mica (Na-mica-4) was synthesized and organofunctional by cationic exchange with an alkylamine, primary amine of 18 carbon atoms (C18-mica-4). Both were characterized by X-ray diffraction, field transmission electron microscopy, surface-specific analysis, differential scanning calorimetry, and thermal gravimetric analysis. In addition, screening cytotoxicity trials were conducted on the human intestinal cell line Caco-2 with C18-mica-4 (0-125 μg/ml). Results: Only one of the endpoints evaluated (the reduction of tetrazolium MTS salt by dehydrogenase enzymes) showed a significant decrease in cellular viability after 48h at the highest concentration tested. C18-mica-4 shows structural resistance to both, gastric and gastrointestinal, digestion. Conclusion: A successful development of a functionalized mica has been made with a promising potential application as a carrier to the drug.

Background: Low bioavailability of anti-diabetic drugs results in the partial absorption of the drug as they are mainly absorbed from the stomach and the lower part of the GIT. Drug bioavailability of anti-diabetic drugs can be significantly increased by prolonging gastric retention time through gastro-retentive dosage form such as floating microspheres. Objective: The study was aimed to develop and characterize resin based floating microspheres of Repaglinide and Metformin for superior and prolonged maintenance of normoglycaemia in type-2 diabetes mellitus. Methods: Repaglinide and metformin were complexed with amberlite resin; later resin complexed drug was encapsulated in Ethylcellulose floating microspheres. Floating microspheres were characterized for morphology, particle size, IR spectroscopy, DSC, in vitro release and buoyancy studies. Further, floating microspheres were tested for in vivo blood glucose reduction potential in Streptozocin- induced diabetic mice. Results: Floating microspheres had a spherical shape and slightly rough surface with the entrapment efficiency in a range of 49-78% for metformin and 52-73% for repaglinide. DSC studies revealed that no chemical interaction took place between polymer and drugs. Floating microspheres showed good buoyancy behavior (P<0.05) and prolonged drug release as compared to plain drug (P<0.05). The blood glucose lowering effect of floating microspheres on Streptozocin induced diabetic rats was significantly greater (P<0.05) and prolonged (#131;12h) and normoglycaemia was maintained for 6hr. Conclusion: Floating microspheres containing drug resin complex were able to prolong drug release in an efficient way for a sustained period of time; as a result, profound therapeutic response was obtained.