Stimuli-sensitive thiolated hyaluronic acid based nanofibers: synthesis, preclinical safety and in vitro anti-HIV activity. (November 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Nanomedicine. Volume 11:Number 22(2016)
• Page Start: 2935
• Page End: 2958
• Publication Date: 2016-11
• Subjects: anti-HIV activity -- electrospinning -- HIV vaginal transmission -- nanofibers -- preclinical safety -- tenofovir -- thiolated hyaluronic acid -- topical microbicide -- vaginal delivery; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm-2016-0103
• Languages: English
• ISSNs: 1743-5889

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.