Low Molecular Weight Sulfated Chitosan Microparticles Efficiently Binds HIV-1 In Vitro: Potential for Microbicide Applications

Background: Human Immunodeficiency Virus type 1 (HIV-1) remains a major global health challenge. Despite advances in antiretroviral therapy, new prevention strategies are needed, particularly topical microbicides capable of blocking the earliest steps of viral entry. HIV-1 attachment relies on interactions with heparan sulfate proteoglycans on host cell surfaces; therefore, sulfated heparan-mimetic polymers have been explored as antiviral agents. In this context, sulfated chitosan microparticles are designed to mimic natural glycosaminoglycan receptors, acting as biomimetic decoys that prevent viral attachment and entry. Methods: Low molecular weight sulfated chitosan (LMW Ch-S) microparticles were synthesized and characterized (FTIR, SEM) following US Patent No. 11,246,839 B2 (Bucarey et al., 2022). Their antiviral activity was evaluated by incubating the microparticles with high-viral-load HIV-1–positive plasma to enable viral binding and removal by pull-down. The performance of the synthesized Ch-S microparticles was compared with established heparinoid controls, including soluble heparin and heparin microparticles. Results: The Ch-S microparticles exhibited stronger virus-binding and neutralizing capacity than all heparinoid comparators, achieving the highest overall reduction in viral load. Subsequent evaluation across multiple tested concentrations confirmed a consistent antiviral effect, indicating that the synthesized Ch-S microparticles maintain robust virus–particle interactions throughout the concentration range examined. Conclusions: These findings demonstrate that LMW Ch-S microparticles possess potent antiviral properties and outperform classical heparinoid materials, supporting their potential application as topical microbicides targeting early HIV-1 entry mechanism.