title: Formulation of tenofovir-loaded functionalized solid lipid nanoparticles intended for HIV prevention.
abstract: 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 (X(1) = bovine serum albumin concentration, X(2) = pH of the aqueous phase, and X(3) = 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 X(1) and X(2) . The produced fSLNs appear noncytotoxic and exhibit a platelet-like shape with respective PMD, EE%, and ζ value of 153 nm, 8.3%, and - 51 mV. 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.
authors: Laboratory of Future Nanomedicine and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64108.
authors: Dima
authors: D
authors: Alukda
authors: Department of Environmental Health and Safety, University of Missouri-Kansas City, Kansas City, Missouri 64110.
authors: Timothy
authors: T
authors: Sturgis
authors: Laboratory of Future Nanomedicine and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64108. Electronic address: youanb@umkc.edu.
authors: Bi-Botti C
authors: BC
authors: Youan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004847:Epithelial Cells / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D010316:Particle Size; D044367:Phase Transition; D011107:Polylysine / Q000737:chemistry; D013499:Surface Properties; D000068698:Tenofovir; D014621:Vagina / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D008055:Lipids; D063065:Organophosphonates; D011107:Polylysine; D006493:Heparin; D000068698:Tenofovir; D000225:Adenine