Stimuli-sensitive thiolated hyaluronic acid based nanofibers: Synthesis, preclinical safety and in vitro anti-HIV activity
Journal
Nanomedicine
Journal Volume
11
Journal Issue
22
Pages
2935-2958
Date Issued
2016
Author(s)
Agrahari V.
Meng J.
Ezoulin M.J.M.
Youm I.
Dim D.C.
Molteni A.
Christenson L.K.
Youan B.-B.C.
Abstract
AIM: 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. CONCLUSION: HA-SH-NFs developed in this study could potentially serve as a safe nanotemplate for topical intravaginal delivery of HIV/AIDS microbicides.
SDGs
Publisher
Future Medicine Ltd.
Type
journal article