Despite current prophylactic strategies, sexually transmitted infections (STIs) remain significant contributors to global health challenges, spurring the development of new multipurpose delivery technologies to protect and treat virus infections. However, there are few methods currently available to prevent – and none-to-date that cure – human immunodeficiency virus (HIV) or combinations of STIs. While current oral and topical pre-exposure prophylaxis have protected against HIV infection, they have primarily relied on antiretrovirals (ARVs) to inhibit infection. Yet, continued challenges with ARVs include daily user adherence and the potential toxicity and antiviral resistance associated with chronic use. The integration of new biological agents may avert some of these adverse effects, while also providing new mechanisms to prevent infection. Of the biologic-based antivirals, Griffithsin (GRFT), has demonstrated potent inhibition of HIV-1 (and a multitude of other viruses), by adhering to and inactivating HIV-1 immediately upon contact. In parallel with the development of GRFT, electrospun fibers (EFs) have emerged as a promising platform to deliver active agents against HIV infection. Here our goal was to extend the mechanistic diversity of active agents and electrospun fibers, by incorporating the biologic GRFT on the EF surface, versus within EFs, to inactivate HIV prior to cellular entry. We fabricated and characterized GRFT-modified EFs (GRFT-EFs) with different surface-modification densities of GRFT, and demonstrated safety and efficacy against HIV-1 infection in vitro We believe this is a unique platform that may be enhanced by incorporation of additional antiviral agents, to prevent STIs via multiple mechanisms.
Griffithsin-Modified Electrospun Fibers as a Delivery Scaffold to Prevent HIV Infection.