Nanoparticle Engineering of Aprepitant Using Nano-by-Design (NbD) Approach.

The aim of this research was to develop a nanosuspension of aprepitant (APT) using the Nano-by-Design approach. A novel microfluidization technology was used for processing the formulation. A 32 full factorial design was used for the optimization of dependent variables, which included critical quality attributes like particle size and polydispersity index. Subsequently, the design space was generated and the optimum formulation was located using desirability constraints followed by its validation.The prepared nanosuspension had a particle size of 721 nm ± 5%, a polydispersity index of 0.106 ± 3%, and a zeta potential of - 8.06 ± 5 mV. Its surface morphology was studied using SEM, DSC, and XRD. It revealed that the prepared nanosuspension had a nano-crystalline nature. The process parameters did not lead to any physicochemical interaction between the drug and excipients. This was confirmed using FTIR analysis. In vitro dissolution studies revealed 100% cumulative drug release over 60 min, showing better results in comparison with pure APT. Thus, it has been shown that microfluidization can be an industrially feasible, novel, green technology for the preparation of a stable APT nanosuspension for improving the dissolution profile of the drug.

Evaluation of Phytopolyphenols for their gp120-CD4 Binding Inhibitory Properties by In Silico Molecular Modelling & In Vitro Cell Line Studies.

BACKGROUND: Lack of effective early-stage HIV-1 inhibitor instigated the need for screening of novel gp120-CD4 binding inhibitor. Polyphenols, a secondary metabolite derived from natural sources are reported to have broad spectrum HIV-1 inhibitory activity. However, the gp120-CD4 binding inhibitory activity of polyphenols has not been analysed in silico yet. OBJECTIVES: To establish the usage of phytopolyphenols (Theaflavin, Epigallocatechin (EGCG), Ellagic acid and Gallic acid) as early stage HIV-1 inhibitor by investigating their binding mode in reported homology of gp120-CD4 receptor complex using in silico screening studies and in vitro cell line studies. METHODS: The in silico molecular docking and molecular simulation studies were performed using Schrödinger 2013-2 suite installed on Fujitsu Celsius Workstation. The in vitro cell line studies were performed in the TZM-bl cell line using MTT assay and ß-galactosidase assay. RESULTS: The results of molecular docking indicated that Theaflavin and EGCG exhibited high XP dock score with binding pose exhibiting Van der Waals interaction and hydrophobic interaction at the deeper site in the Phe43 cavity with Asp368 and Trp427. Both Theaflavin and EGCG form a stable complex with the prepared HIV-1 receptor and their binding mode interaction is within the vicinity 4 Å. Further, in vitro cell line studies also confirmed that Theaflavin (SI = 252) and EGCG (SI = 138) exert better HIV-1 inhibitory activity as compared to Ellagic acid (SI = 30) and Gallic acid (SI = 34). CONCLUSION: The results elucidate a possible binding mode of phytopolyphenols, which pinpoints their plausible mechanism and directs their usage as early stage HIV-1 inhibitor.

Preparation and Characterization of Solid Lipid Nanoparticles-Based Gel for Topical Delivery.

Solid lipid nanoparticles (SLNs) have been extensively investigated for effective delivery of both hydrophilic and lipophilic drugs by topical route. There are several scalable techniques for the preparation of SLNs such as homogenization, microemulsion template, and solvent emulsification diffusion. This chapter describes step-wise methodology for the preparation and characterization of SLNs using solvent emulsification diffusion method. Tretinoin, a lipophilic entity, was chosen as a model drug. The critical aspects and the important interpretations with respect to the preparation and characterization of SLNs are reported in "Notes" section.

Tetrahydrocurcumin-loaded vaginal nanomicrobicide for prophylaxis of HIV/AIDS: in silico study, formulation development, and in vitro evaluation.

A vaginal microbicide is a front-line women-dependent approach and an alternative to a condom for prevention of unprotected sexual intercourse-associated HIV. The microbicide research is still in its infancy with several products in the clinical studies being reported to have good efficacy, safe, but with poor adherence. One such molecule reported with an excellent efficacy when tested preclinically is curcumin, a natural polyphenol derived from Curcuma longa. Despite its potential HIV-1 inhibitory activity, it has intense yellow color staining properties, which would result in poor consumer compliance and adherence for vaginal application. To address this issue, tetrahydrocurcumin (THC), a colorless derivative of curcumin, was subjected to in silico screening (molecular docking and dynamics simulation studies) using homology model of gp120-CD4 binding. It was found that THC exhibited equivalent gp120-CD4 binding inhibitory activity as compared with curcumin due to its stable hydrophobic interactions with residues Asp368 and Trp427 deeper in the Phe43 cavity of CD4 receptor. Hence, it can be effectively used as a potential microbicide candidate. THC, a BCS Class II molecule exhibits poor solubility, spreadability, and intracellular uptake when used in the conventional form. Thus, it was decided to develop a lipid-based nanomicrobicide gel for delivery of THC. The developed THC-loaded o/w microemulsion gel was characterized for physicochemical properties (globule size, drug content, drug release, and permeation) and further used for in vitro cell line studies (cell viability, cellular uptake, and anti-HIV activity). The developed formulation was found to be stable with coitus-independent release profile and exhibited a rapid time-independent intracellular uptake. In addition, it exhibited a fourfold increase in efficacy as compared with conventional THC. Thus, the novel THC-loaded o/w microemulsion gel exhibited the potential for prevention of HIV-1 infection associated with unprotected sexual intercourse.