Comparative Biophysical Properties of Tenofovir-Loaded, Thiolated and Nonthiolated Chitosan Nanoparticles Intended for HIV Prevention

Abstract

Aim: 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. Materials & 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. Conclusion: 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.

Original submitted 22 May 2012; Revised submitted 13 June 2013

Keywords::

• HIV prevention
• mucoadhesion
• nanoparticle
• tenofovir
• thiolated chitosan
• vaginal drug delivery

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Allergy and Infectious Diseases or the National Institute of Health.

Financial & competing interests disclosure

The work presented was supported by Grant Number R01A1087304 from the National Institute of Allergy and Infectious Diseases (MD, USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgements

The authors are grateful to VM Dusevich (School of Dentistry, University of Missouri, USA) for the transmission electron microscopy images. The authors would also like to thank C Forster (Fairview Farm Meat Co., KS, USA) for kindly providing the fresh porcine vaginal tissue.

Additional information

Funding

The work presented was supported by Grant Number R01A1087304 from the National Institute of Allergy and Infectious Diseases (MD, USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.