Formulation of tenofovir‐loaded functionalized solid lipid nanoparticles intended for HIV prevention

• Published in: Journal of pharmaceutical sciences 2011-08, Vol.100 (8), p.3345-3356
• Main Authors: Alukda, Dima, Sturgis, Timothy, Youan, Bi‐Botti C.
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - chemistry; Adenine - therapeutic use; Adenine - toxicity; Administration, Intravaginal; Anti-HIV Agents - chemistry; Anti-HIV Agents - therapeutic use; Anti-HIV Agents - toxicity; Biological and medical sciences; Cell Culture Techniques; Cell Line; Cell Survival - drug effects; Chemistry, Pharmaceutical; coating; colloids; Drug Carriers - chemistry; Epithelial Cells - drug effects; Epithelial Cells - ultrastructure; Female; formulation; functionalization; General pharmacology; Heparin - chemistry; HIV Infections - prevention & control; HIV prevention; Humans; lipids; Lipids - chemistry; Medical sciences; Microscopy, Electron, Transmission; nanoparticles; Nanoparticles - chemistry; Organophosphonates - chemistry; Organophosphonates - therapeutic use; Organophosphonates - toxicity; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Polylysine - chemistry; Surface Properties; Tenofovir; topical drug delivery; Vagina - drug effects; Vagina - ultrastructure
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22529

The objective of this study is to engineer polylysine–heparin functionalized solid lipid nanoparticles (fSLNs) for the use of a vaginal microbicide delivery template for HIV prevention. The fSLNs are prepared using a modified phase‐inversion technique followed by a layer‐by‐layer deposition method. The Box–Behnken experimental design is used to analyze the influence of three factors (X1 = bovine serum albumin concentration, X2 = pH of the aqueous phase, and X3 = lipid amount) on the particle mean diameter (PMD) measured by dynamic light scattering (DLS). Tenofovir is used as a model anti‐HIV microbicide. The SLNs are also characterized for morphology, zeta potential (ζ ), percent drug encapsulation efficiency (EE%), and cytotoxicity on a human vaginal epithelial cell line by electron microscopy, DLS, ultraviolet, and fluorescence spectroscopy, respectively. The statistical model predicts particle size (Y) with 90% confidence and the Y values are significantly affected by X1 and X2. The produced fSLNs appear noncytotoxic and exhibit a platelet‐like shape with respective PMD, EE%, and ζ value of 153nm, 8.3%, and − 51mV. These fSLNs intended to be administered topically have the potential to enhance cellular uptake of hydrophobic microbicides and outdistance the virus during the HIV/AIDS infection process, possibly leading to more effective prevention of the disease transmission. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3345–3356, 2011