Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and

• Published in: Nanomedicine (London, England) England), 2016-11, Vol.11 (22), p.2935-2958
• Main Authors: Agrahari, Vivek, Meng, Jianing, Ezoulin, Miezan JM, Youm, Ibrahima, Dim, Daniel C, Molteni, Agostino, Hung, Wei-Ting, Christenson, Lane K, Youan, Bi-Botti C
• Format: Article
• Language: English
• Subjects: anti-HIV activity; electrospinning; HIV vaginal transmission; nanofibers; preclinical safety; tenofovir; thiolated hyaluronic acid; topical microbicide; vaginal delivery
• ISSN: 1743-5889; 1748-6963
• DOI: 10.2217/nnm-2016-0103

To develop a seminal enzyme bioresponsive, mucoadhesive nanofibers (NFs) as safe and effective nanocarriers for the prevention of HIV vaginal transmission. A novel thiolated hyaluronic acid (HA-SH) polymer was synthesized to fabricate tenofovir (TFV)-loaded electrospun NFs (HA-SH-NFs) and characterized . 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. HA-SH-NFs developed in this study could potentially serve as a safe nanotemplate for topical intravaginal delivery of HIV/AIDS microbicides.