title: Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and in vitro anti-HIV activity.
abstract: OBJECTIVE
  To develop a seminal enzyme bioresponsive, mucoadhesive nanofibers (NFs) as safe and effective nanocarriers for the prevention of HIV vaginal transmission.
  
  
  METHODS
  A novel thiolated hyaluronic acid (HA-SH) polymer was synthesized to fabricate tenofovir (TFV)-loaded electrospun NFs (HA-SH-NFs) and characterized in vitro/in vivo.
  
  
  RESULTS
  A triggered drug release (87% w/w) from the engineered HA-SH-NFs (mean diameter ∼75 nm) occured within 1 h under the influence of seminal hyaluronidase enzyme. HA-SH-NFs were noncytotoxic, induced no damage on the C57BL/6 mice genital-tract and other organs. No significant CD45 cell-infiltration and changes in cytokines level in cervicovaginal tissues were observed. HA-SH-NFs significantly enhanced both TFV retention and bioavailability in vaginal tissue compared with the 1% TFV-gel. The anti-HIV activity of TFV (on pseudotyped virus followed by luciferase assay) was not adversely affected by the electrospinning process.
  
  
  CONCLUSIONS
  HA-SH-NFs developed in this study could potentially serve as a safe nanotemplate for topical intravaginal delivery of HIV/AIDS microbicides.
authors: Laboratory of Future Nanomedicines & Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors: Vivek
authors: V
authors: Agrahari
authors: Laboratory of Future Nanomedicines & Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors: Jianing
authors: J
authors: Meng
authors: Laboratory of Future Nanomedicines & Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors: Miezan Jm
authors: MJ
authors: Ezoulin
authors: Laboratory of Future Nanomedicines & Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.|Hough Ear Institute, Oklahoma City, OK 73112, USA.
authors: Ibrahima
authors: I
authors: Youm
authors: School of Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA.
authors: Daniel C
authors: DC
authors: Dim
authors: School of Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA.
authors: Agostino
authors: A
authors: Molteni
authors: Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Wei-Ting
authors: WT
authors: Hung
authors: Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors: Lane K
authors: LK
authors: Christenson
authors: Laboratory of Future Nanomedicines & Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108, USA.
authors: Bi-Botti C
authors: BC
authors: Youan
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D051379:Mice; D057139:Nanofibers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D060737:Reproductive Tract Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D013438:Sulfhydryl Compounds / Q000737:chemistry; D000068698:Tenofovir / Q000008:administration & dosage / Q000737:chemistry; D014621:Vagina / Q000187:drug effects / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D013438:Sulfhydryl Compounds; D006820:Hyaluronic Acid; D000068698:Tenofovir
keywords: HIV vaginal transmission; anti-HIV activity; electrospinning; nanofibers; preclinical safety; tenofovir; thiolated hyaluronic acid; topical microbicide; vaginal delivery