Pharmaceutical Nanotechnology - Volume 7, Issue 5, 2019

Background: Many researchers have prepared and evaluated nanosponges and claimed their advantages as an effective drug carrier, especially it was observed prominently in case of anti-fungal drugs. The materials employed to synthesize nanosponges were mainly crosslinking agents, different beta-cyclodextrin and other cellulose-based polymers. Many of them had used ratio proportions of cross-linking agents, d polymers to synthesize these nanosponges which ultimately produce a porous mesh-like network known as nanosponges where actually drug is encapsulated or loaded. Objective: In the present investigation, we observed the effect of various levels of crosslinking agents and beta-cyclodextrin concentrations on porosity, drug encapsulation, zeta potential and drug release by employing the quality by design approach to synthesize nanosponges rather than merely keeping both concentrations in proportions. Methods: We have slightly modified the method reported earlier i.e. melting method in which we have used rota evaporator receiver vessel for melting cross-linking agent and beta- cyclodextrin, rotated at 20 RPM at 100°C. Results: In a quality by design approach, we observed that out of four dependent variables i.e. porosity, drug loading, zeta potential and drug release, three significantly depend on the crosslinking of beta-cyclodextrin molecules which is highly appreciated by the amount of cross-linking agent present in the reaction. The pharmacokinetics of Imatinib loaded optimized nanosponges were compared with the reference product to observe the pattern of absorption and disposition. Conclusion: Nanosponges synthesized by optimization technique could be effective means of anti-cancer drug oral administration as they encapsulate the drug effectively and offer a prolonged release of drug which gradually releases the drug and avoids unnecessary exposure of the drug.

Background: There is an unmet need for optimized drug delivery system of psoriasis therapy because of various issues like adverse reaction, permeation problem associated with convention treatment (oral and topical) available for psoriasis. Objective: The goal was to develop an ethosomal gel of methotrexate (MTX)-incorporated ethosomes and salicylic acid (SA) and to evaluate and study its ethosomal gel potential in Imiquimod-induced psoriasis animal model to treat symptoms of psoriasis. Methods: MTX-SA ethosomal gel was prepared by the cold method given by Touitou et al. and optimized by comparing it with MTX ethosomal gel and drug solution. Particle size, zeta potential, entrapment efficiency, and ex-vivo study were selected as the critical quality checking attributes. Psoriatic Area and Severity Index (PASI) score & histopathological examination were done for checking Antipsoriatic potential of MTX-SA ethosomal gel by using the imiquimod-induced psoriasis model. Results: Optimized MTX-SA exhibited a particle size of 376.04 ± 3.47nm, EE(Entrapment efficiency) of 91.77 ± 0.02%. At the end of 24h, MTX-SA ethosomal gel exhibited a slow and prolonged release of MTX (26.13 ± 1.61% versus 6.97 ± 0.06%) compared to MTX drug solution. It also attributes of 43% retention study as compared to drug solution (13%). Besides, it essentially decreased the PASI score with the recuperation of normalcy of the mice's skin, while the MTX-SA gel displayed indications of gentle hyper and parakeratosis toward the completion of investigation when contrasted with the blank gel. Conclusion: The developed MTX-SA ethosomal gel formulation can be a promising alternative to existing MTX formulation in topically treating psoriasis.

Background: Dronedarone HCl (DRD), owing to its poor aqueous solubility and extensive presystemic metabolism shows low oral bioavailability of about 4% without food, which increases to approximately 15% when administered with a high fat meal. Objective: Solid lipid nanoparticles (SLN) were designed with glyceryl monstearate (GMS) in order to improve oral bioavailability of DRD. Methods: Hot homogenization followed by probe sonication was used to prepare SLN dispersions. Box-Behnken design was used to optimize manufacturing conditions. SLN were characterized for particle size, zeta potential, entrapment efficiency, physical state and in vitro drug release. Pharmacokinetics and intestinal uptake study of dronedarone HCl loaded solid lipid nanoparticles (DRD-SLN) in the presence and absence of endocytic uptake inhibitor, chlorpromazine (CPZ) was performed with conscious male Wistar rats. Results: Optimized formulation of SLN showed particle size of 233 ± 42 nm and entrapment efficiency of 87.4 ± 1.29%. Results of pharmacokinetic studies revealed enhancement of bioavailability of DRD by 2.68 folds from SLN as compared to DRD suspension. Significantly reduced bioavailability of DRD-SLNs in the presence of chlorpromazine, demonstrated the role of endocytosis in uptake of SLN formulation. Conclusion: These results indicated that dronedarone HCl loaded SLN could potentially be exploited as a delivery system for improving oral bioavailability by minimizing first pass metabolism.

Background: Acyclovir use is limited by a high frequency of administration of five times a day and low bioavailability. This leads to poor patient compliance. Objectives: To overcome the problem of frequent dosing, we used nanotechnology platform to evaluate the proof of concept of substituting multiple daily doses of acyclovir with a single dose. Methods: Acyclovir was formulated as solid lipid nanoparticles (SLN). The nanoparticles were characterized for particle size, surface charge and morphology and in vitro drug release. The pharmacokinetic and pharmacodynamic of SLN acyclovir were compared with conventional acyclovir in a mouse model. Results: SLN showed drug loading of 90.22% with 67.44% encapsulation efficiency. Particle size was found to be of 131 ± 41.41 nm. In vitro drug release showed 100% release in SIF in 7 days. AUC0-∞ (119.43 ± 28.74 μg/ml h), AUMC0-∞ (14469 ± 4261.16 μg/ml h) and MRT (120.10 ± 9.21 h) were significantly higher for ACV SLN as compared to ACV AUC0-∞ (12.22 ± 2.47 μg/ml h), AUMC0-∞ (28.78 ± 30.16 μg/ml h) and MRT (2.07 ± 1.77 h), respectively (p<0.05). In mouse model, a single dose of ACV SLN was found to be equivalent to ACV administered as 400mg TID for 5 days in respect to lesion score and time of healing. Conclusion: The proof of concept of sustained-release acyclovir enabling administration as a single dose was thus demonstrated.

Background: Multi-walled carbon nanotubes (MWCNT) adjunct to molecularly imprinted polymers (MIP) have advantages of the large surface area of nanoparticles and selectivity of MIPs for selective extraction of tetradifon as a widely used pesticide in date palm. Objectives: The main aims were the use of experimental design, electrochemical synthesis and ultra-high performance liquid chromatography (UHPLC) to develop a simple, reliable and precise pesticide residue analysis method as an important aspect of food and drug quality control for the determination of tetradifon in date palms. Methods: An MIP in the presence of MWCNT was synthesized by cyclic voltammetric technique on a steel rod to produce a composite of MIP-MWCNTs for stir bar extraction of tetradifon residue in date samples. The experimental design was used to optimize MIPMWCNT composite synthesis through the screening of eight variables. The composite was characterized by scanning electron microscopy (SEM). Tetradifon was determined in extracted samples by UHPLC under optimum conditions. Results: A very thin film was made by MIP-MWCNT coated on a steel rod which was repeatable and had good adhesion and persistence. The detection limit (LOD) and the quantification limit (LOQ) of the method were measured as 16 and 49 ng/ml, respectively. Average recovery of tetradifon at the two spiked levels was observed to be as low as 86.5% to 90.7% (RSD from 0.79% to 1.04%). Conclusion: The low cost, high selectivity, good reproducibility, acceptable intra and inter day precision and accuracy developed method were successfully applied to determine tetradifon residue in date samples purchased from a local market.