Nanomaterial Strategies to Enhance Antiretroviral Efficacy for Vaginal Drug Delivery
Krogstad, Emily Anne
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HIV continues to infect millions of people worldwide, and without an effective vaccine or cure available, there is need for new methods to prevent infection. Women are disproportionately impacted by HIV due to biologic vulnerabilities and social inequalities, and are especially at risk in places with high HIV incidence like sub-Saharan Africa. Topical microbicides are products in development that can be vaginally administered to prevent HIV infection. Since microbicides are a female-initiated product, they would fill an important gap in the array of currently available prevention options that are targeted toward men such as circumcision and condoms. Unfortunately, only one topical microbicide to date has demonstrated modest efficacy in clinical trials, with an overall 39% reduction in HIV acquisition. New strategies are needed to improve the effectiveness of topical microbicides. In this work, we explored several nanomaterials including nanoparticles, nanofibers, and nanoparticle/nanofiber composites as novel drug delivery platforms for topical microbicides. We hypothesized that by engineering nanocarriers to deliver multiple drugs in combination, provide sustained release, and have tailored interactions with cervicovaginal mucus, nanomaterials would allow for more effective delivery of antiretroviral drugs to vaginal tissue. We also explored nanofibers as a delivery vehicle for both drugs and nanoparticles and evaluated their ability to enhance vaginal retention relative to liquid-based dosage forms. We found that both nanoparticles and nanofibers offer much potential for enhancing drug delivery to vaginal tissue. Nanoparticles were developed to load several different antiretroviral drugs and show enhanced efficacy against HIV-1 in vitro compared to free drug alone. Nanofibers were demonstrated to be able to load many agents relevant to vaginal drug delivery at remarkably high levels (up to 60% by mass), provide both quick and sustained drug release, release active drug with action against HIV-1, and act as a physical and chemical barrier to sperm. Finally, nanoparticle/nanofiber composites were found to dramatically enhance nanoparticle and drug retention in the reproductive tract of mice, providing proof-of-concept for a new platform for the vaginal administration of nanoparticles that is both solid-state and practical to administer. We expect that results from this work will be impactful not only for the microbicide field, but also for other applications, including the prevention and treatment of other sexually transmitted infections, mucosal vaccination, and topical drug delivery to mucosal sites.
- Bioengineering