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

## TL;DR

Low-molecular-weight sulfated chitosan microparticles bind and neutralize HIV-1 in lab tests, showing promise as a microbicide to prevent HIV infection.

## Contribution

Low-molecular-weight sulfated chitosan microparticles are shown to outperform heparin-based materials in binding and neutralizing HIV-1.

## Key findings

- Chi-S microparticles reduced HIV-1 viral load by up to 70%, outperforming heparin and heparin microparticles.
- The antiviral effect of Chi-S microparticles was consistent across multiple tested concentrations.
- Chi-S microparticles bind HIV-1 more effectively than established heparinoid controls.

## Abstract

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 Chi-S) microparticles were synthesized and characterized (SEM, EDS, DLS, FTIR) following US Patent No. 11,246,839 B2. Their antiviral activity was evaluated by incubating the microparticles with high-viral-load HIV-1-positive plasma (~3.5 × 106 copies/mL) to enable viral binding and removal by pull-down. The performance of the synthesized Chi-S microparticles was compared with established heparinoid controls, including soluble heparin and heparin microparticles. Results: Chi-S microparticles exhibited stronger virus-binding and neutralizing capacity than all heparinoid comparators, achieving up to 70% reduction in viral load relative to untreated HIV-1 plasma. In comparison, soluble heparin and heparin microparticles reduced viral load by approximately 53% and 60%, respectively. Subsequent evaluation across multiple tested concentrations confirmed a consistent antiviral effect, indicating that the synthesized Chi-S microparticles maintain robust virus–particle interactions throughout the concentration range examined. Conclusions: These findings demonstrate that LMW Chi-S microparticles possess potent antiviral properties and outperform classical heparinoid materials, supporting their potential application as topical microbicides targeting early HIV-1 entry mechanisms.