title: pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission.
abstract: This study is designed to test the hypothesis that tenofovir (TNF) or tenofovir disoproxil fumarate (TDF) loaded nanoparticles (NPs) prepared with a blend of poly(lactic-co-glycolic acid) (PLGA) and methacrylic acid copolymer (Eudragit® S-100, or S-100) are noncytotoxic and exhibit significant pH-responsive release of anti-HIV microbicides in the presence of human semen fluid simulant (SFS). After NPs preparation by emulsification diffusion, their size, encapsulation efficiency (EE%), drug release profile, morphology, and cytotoxicity are characterized by dynamic light scattering, spectrophotometry, transmission electron microscopy, and cellular viability assay/transepithelial electrical resistance measurement, respectively. Cellular uptake was elucidated by fluorescence spectroscopy and confocal microscopy. The NPs have an average size of 250 nm, maximal EE% of 16.1% and 37.2% for TNF and TDF, respectively. There is a 4-fold increase in the drug release rate from the 75% S-100 blend in the presence of SFS over 72 h. At a concentration up to 10mg/ml, the PLGA/S-100 NPs are noncytotoxic for 48 h to vaginal endocervical/epithelial cells and Lactobacillus crispatus. The particle uptake (∼ 50% in 24h) by these vaginal cell lines mostly occurred through caveolin-mediated pathway. These data suggest the promise of using PLGA/S-100 NPs as an alternative controlled drug delivery system in intravaginal delivery of an anti-HIV/AIDS microbicide.
authors: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors: Tao
authors: T
authors: Zhang
authors: Timothy F
authors: TF
authors: Sturgis
authors: Bi-Botti C
authors: BB
authors: Youan
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004339:Drug Compounding; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D007778:Lactobacillus / Q000187:drug effects; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D063065:Organophosphonates / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011109:Polymethacrylic Acids / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D000068698:Tenofovir; D014621:Vagina / Q000166:cytology / Q000187:drug effects / Q000382:microbiology
chemical_list: D019380:Anti-HIV Agents; D004337:Drug Carriers; D063065:Organophosphonates; D011109:Polymethacrylic Acids; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C038300:methylmethacrylate-methacrylic acid copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000068698:Tenofovir; D000225:Adenine