Current Drug Delivery - Volume 16, Issue 4, 2019

Chitosan is a polycationic natural polymer which is abundant in nature. Chitosan has gained much attention as natural polymer in the biomedical field. The up to date drug delivery as well as the nanotechnology in controlled release of drugs from chitosan nanofibers are focused in this review. Electrospinning is one of the most established and widely used techniques for preparing nanofibers. This method is versatile and efficient for the production of continuous nanofibers. The chitosan-based nanofibers are emerging materials in the arena of biomaterials. Recent studies revealed that various drugs such as antibiotics, chemotherapeutic agents, proteins and anti-inflammatory analgesic drugs were successfully loaded onto electrospun nanofibers. Chitosan nanofibers have several outstanding properties for different significant pharmaceutical applications such as wound dressing, tissue engineering, enzyme immobilization, and drug delivery systems. This review highlights different issues of chitosan nanofibers in drug delivery applications, starting from the preparation of chitosan nanofibers, followed by giving an idea about the biocompatibility and degradation of chitosan nanofibers, then describing how to load the drug into the nanofibers. Finally, the major applications of chitosan nanofibers in drug delivery systems.

Background: Over the past century, the prevalence of skin diseases has substantially increased. These diseases present a significant physical, emotional and socio-economic burden to the society. Such conditions are also associated with a multitude of psychological traumas to the suffering patients. The effective treatment strategy implicates targeting of drugs to the skin. The field of drug targeting has been revolutionized with the advent of nanotechnology. The emergence of stimulus-responsive nanoplatforms has provided remarkable control over fundamental polymer properties for external triggers. This enhanced control has empowered pioneering approaches in the treatment of chronic inflammatory skin diseases. Objective: Our aim was to investigate the studies on smart nanoplatforms that exploit the altered skin physiology under diseased conditions and provide site-specific controlled drug delivery. Method: All literature search regarding the advances in stimulus sensitive smart nanoplatforms for skin diseases was done using Google Scholar and Pubmed. Conclusion: Various stimuli explored lately for such nano platforms are pH, temperature, light and magnet. Although, the scientists have actively taken up this research topic but there are still certain lacunaes associated which have been discussed in this review. Further, an interdisciplinary collaboration between the healthcare providers and pharmacists is a pivotal requirement for such systems to be available for patients.

On account of the advantages of transdermal delivery and the application situation of transcutaneous technology in transdermal delivery, the article critically comments on nanosystems as permeation enhancement model. Nanosystems possess great potential for transcutaneous drug delivery. This review focuses on recent advances in lipid-based nanocarriers, including liposome, transfersomes, ethosomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers and combination application of the lipid-based nanocarriers with microneedle, iontophoresis, electroporation and sonophoresis in the field for the development of the transdermal drug delivery system. We attempted to give an overview of lipid-based nanocarriers with the aim to improve transdermal and dermal drug delivery. A special focus is given to the nanocarrier composition, characteristic and interaction mechanisms through the skin. Recent combination applications of lipid-based nanocarriers with the physical penetration technology demonstrate the superiority of the combined use of nanocarriers and physical methods in drug penetration enhancement compared to their single use. In the future, lipidbased nanocarriers will play a greater role in the field of transdermal and dermal drug delivery.

Background: Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-emulsify in GIT and improve the absorption and bioavailability. Probucol (PB) is a highly lipophilic compound with very low and variable bioavailability. Objective: The objectives of this study were to examine the stability and conduct bioavailability of the prepared Probucol Self-Emulsified Drug Delivery System (PBSEDDS) in human volunteers. Methods: The methods included preparation of different PBSEDDS using soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (co-surfactant). The formulations were characterized in vitro for spontaneity of emulsification, droplet size, turbidity and dissolution in water after packing in HPMC capsules. The optimized formulations were evaluated for stability at different storage temperatures and human bioavailability compared with the drug dissolved in soybean oil (reference). Results: The results showed that formulations (F1-F4) were stable if stored at 20 °C. The mean (n=3) pharmacokinetic parameters for stable formulations were: The Cmax, 1070.76, 883.16, 2876.43, 3513.46 and 1047.37 ng/ml; the Tmax, 7.93, 7.33, 3.96, 3.67 and 4.67 hr.; the AUC (0-t), 41043.41, 37763.23, 75006.26, 46731.36 and 26966.43 ng.hr/ml for F1, F2, F3, F4 and reference, respectively. The percentage relative bioavailability was in this order: F3> F4> F1> F2>. Conclusion: In conclusion, the PBSEDDS formulations were stable at room temperature. F4 showed the highest Cmax and the shortest Tmax. All the formulations showed significant enhancement of bioavailability compared with the reference. The results illustrated the potential use of SEDDS for the delivery of probucol hydrophobic compound.

Objective: In this study, an injectable Sucrose Acetate Isobutyrate (SAIB) drug delivery system (SADS) was designed and fabricated for the sustained release of Ropivacaine (RP) to prolong the duration of local anesthesia. Methods: By mixing SAIB, RP, and N-methyl-2-pyrrolidone, the SADS was prepared in a sol state with low viscosity before injection. After subcutaneous injection, the pre-gel solution underwent gelation in situ to form a drug-released depot. Result: The in vitro release profiles and in vivo pharmacokinetic analysis indicated that RP-SADS had suitable controlled release properties. Particularly, the RP-SADS significantly reduced the initial burst release after subcutaneous injection in rats. Conclusion: In a pharmacodynamic analysis of rats, the duration of nerve blockade was prolonged by over 3-fold for the RP-SADS formulation compared to RP solution. Additionally, RP-SADS showed good biocompatibility in vitro and in vivo. Thus, the SADS-based depot technology is a safe drug delivery strategy for the sustained release of local anesthetics with long-term analgesia effects.

Purpose: As an anti-retroviral Protease Inhibitor (PI), Indinavir (IDV) is part of the regimen known as Highly Active Anti-Retroviral Therapy (HAART) widely used for Human Immunodeficiency Virus (HIV) infection. The drug efficiency in treatment of the brain manifestations of HIV is, however, limited which is mainly due to the efflux by P-glycoprotein (P-gp) expressed at the Blood-Brain Barrier (BBB). Methods: To overcome the BBB obstacle, NLCs were used in this study as carriers for IDV, which were optimized through two steps: a “one-factor-at-a-time” screening followed by a systematic multiobjective optimization. Spherical smooth-surfaced Nanoparticles (NPs), average particle size of 161.02±4.8 nm, Poly-Dispersity Index (PDI) of 0.293±0.07, zeta potential of -40.62±2.21 mV, entrapment efficiency of 93±1.58%, and loading capacity of 9.15±0.15% were obtained after optimization which were, collectively, appropriate in terms of the objective of this study. Result: The surface of the optimized NPs was, then, modified with human Transferrin (TR) to improve the drug delivery. The particle size, zeta potential, and PDI of the TR-modified NLCs were 185.29±6.7nm, -28.68±3.37 mV, and 0.247±0.06, respectively. The in vitro release of IDV molecules from the NPs was best fitted to the Weibull model indicating hybrid diffusion/erosion behavior. Conclusion: As the major in vivo findings, compared to the free drug, the NLCs and TR-NLCs displayed significantly higher and augmented concentrations in the brain. In this case, NLC and TR-NLC were 6.5- and 32.75-fold in their values of the brain uptake clearance compared to free drug.

Background: Capsules containing a dye were prepared by the LbL method with iron oxide nanoparticles (50 nm) in different layers of the shell. Method: The capsules were dispersed in a gel and subjected to focused ultrasonic irradiation at three different powers and exposure times. Result: It was found that the inclusion of iron oxide magnetic nanoparticles in any of the polyelectrolyte shells (4, 6, 8 and 10) strengthened the capsules with respect to capsules without nanoparticles. Incorporation of nanoparticles in shell 8 provided the most resistance to fragmentation under focused ultrasonic irradiation. The relative degree of capsule stability is dependent on both the power of the ultrasound and the exposure time. Conclusion: The presence of iron oxide nanoparticles not only conferred more resistance to fragmentation but also provided a route to protein labelled dye release through sonoporation that was not present for capsules without nanoparticles.

Background: Gefitinib (GEF), the kinase inhibitor, is presently available as tablets to be taken orally in high doses of 250-500 mg per day due to its poor solubility. The solubility issues affect not only its onset of action but also the bioavailability. These drawbacks foresight the need to have an alternate dosage form, preferably a sustained release formulation. Methods: In the present study, microparticles were prepared by emulsion solvent evaporation using PLGA 50:50 (GEF-PLGA MP). A 32 factorial design was used to optimize the critical quality parameters to the set mean particle size in the range of 7.4±2.5 μm and entrapment efficiency of 80%. SEM microscopy of the prepared microparticles confirmed to have a spherical smooth shape. The GEFPLGA- MPs sustained the release of GEF for 72 hours. The first-order kinetics ruled the mechanism of drug release and was predicted to follow Fickian diffusion. Result: Anticancer efficacy was judged by the cytotoxicity studies using the L132 lung cancer cells. MTT assay showed 3-fold enhanced cytotoxicity of GEF loaded microparticles against L132 cells as compared to plain GEF. Conclusion: It was concluded that gefitinib can be efficiently loaded into the biodegradable polymer PLGA to provide sustained release of the drug.

Purpose: The purpose of this study was to develop a new PLGA based microsphere formulation aimed to release the olanzapine for the period of one month which will result in increased compliance. Methods: Microspheres loaded with olanzapine were prepared using oil in water emulsion and solvent evaporation technique. The microspheres were characterized by surface morphology, shape, size, bulk density, encapsulation efficiency, and Fourier transform infrared spectrometry. In vitro release studies were performed in phosphate buffer at 37°C and in vivo studies were conducted on male Sprague- Dawley rats. Results: The morphological results indicated that microspheres produced were having a smooth surface, spherical shape and the size in the range from 9.71 to 19.90 μm mean diameter. Encapsulation efficiency of olanzapine loaded microspheres was in the range of 78.53 to 96.12% and was affected by changing the ratio of lactic to glycolic acid in copolymer PLGA. The properties of PLGA and other formulation parameters had a significant impact on in vitro and in vivo release of drug from microspheres. In vitro release kinetics revealed that release of drug from microspheres is by both non-Fickian diffusion and erosion of PLGA polymer. In vivo data indicated an initial burst release and then sustained release depending on properties of PLGA, microsphere size, and bulk density. Conclusion: This study indicates that microsphere formulations developed with PLGA (75:25) and PLGA (85:15) have provided a sufficient steady release of drug for at least 30 days and can be potential candidates for 30-day depot injection drug delivery of olanzapine.