title: Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention.
abstract: OBJECTIVE
  This study is designed to test the hypothesis that tenofovir-loaded (an anti-HIV microbicide) chitosan-thioglycolic acid-conjugated (CS-TGA) nanoparticles (NPs) exhibit superior biophysical properties for mucoadhesion compared with those of native CS NPs.
  
  
  METHODS
  The NPs are prepared by ionotropic gelation. The particle mean diameter, encapsulation efficiency and release profile are analyzed by dynamic light scattering and UV spectroscopy, respectively. The cytotoxicity, cellular uptake and uptake mechanism are assessed on VK2/E6E7 and End1/E6E7 cell lines by colorimetry/fluorimetry, and percentage mucoadhesion is assessed using porcine vaginal tissue.
  
  
  RESULTS
  The mean diameter of the optimal NP formulations ranges from 240 to 252 nm, with a maximal encapsulation efficiency of 22.60%. Tenofovir release from CS and CS-TGA NPs follows first-order and Higuchi models, respectively. Both NPs are noncytotoxic in 48 h. The cellular uptake, which is time dependent, mainly occurs via the caveolin-mediated pathway. The percentage of mucoadhesion of CS-TGA NPs is fivefold higher than that of CS NPs, and reached up to 65% after 2 h.
  
  
  CONCLUSIONS
  Collectively, CS-TGA NPs exhibit superior biophysical properties and can potentially maximize the retention time of a topical microbicide, such as tenofovir, intended for the prevention of HIV transmission.
authors.affiliation: Laboratory of Future Nanomedicines & Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri, Kansas City, MO 64108, USA.
authors.forename: Jianing
authors.initials: J
authors.lastname: Meng
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Vivek
authors.initials: V
authors.lastname: Agrahari
authors.forename: Miezan J
authors.initials: MJ
authors.lastname: Ezoulin
authors.forename: Bi-Botti C
authors.initials: BB
authors.lastname: Youan
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage; D022461:Caveolins / Q000737:chemistry; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D005470:Fluorometry; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D063065:Organophosphonates / Q000008:administration & dosage*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013552:Swine; D000068698:Tenofovir; D013864:Thioglycolates / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D022461:Caveolins; D063065:Organophosphonates; D013438:Sulfhydryl Compounds; D013864:Thioglycolates; C017487:2-mercaptoacetate; D048271:Chitosan; D000068698:Tenofovir; D000225:Adenine
keywords: HIV prevention; mucoadhesion; nanoparticle; tenofovir; thiolated chitosan; vaginal drug delivery