# Bioresponsive Hydrogel for On-Demand Nonhormonal Contraception

## TL;DR

A bioresponsive hydrogel is developed as a nonhormonal contraceptive that physically blocks sperm migration when exposed to semen.

## Contribution

A drug-free, bioresponsive hydrogel is introduced that forms a physical barrier to sperm upon contact with seminal fluid.

## Key findings

- The hydrogel increases resistance to spreading when exposed to simulated seminal fluid.
- The hydrogel reduces in vitro sperm migration by 97% and significantly lowers sperm motility.
- Safety assessments confirm a vaginal safety profile comparable to approved products.

## Abstract

The utility of bioresponsive multifunctional hydrogel compositions for biomedical applications is rapidly increasing due to the diverse array of biological stimuli that can profoundly alter physicochemical gel properties that benefit therapeutic interventions. The purpose of this research is to explore a bioresponsive hydrogel as a drug-free bioengineering concept to fortify the natural physical contraceptive barriers at the cervicovaginal junction. The results of this research demonstrate that a hydrogel comprising 4% (w/w) Carbopol® 974P and 4% (w/w) polyvinylpyrrolidone (CP4%/PVP4%) undergoes bioresponsive structural changes in the presence of simulated seminal fluid, pH 7.7, (SFS) that increases the work required to spread the gel under physiologically relevant vaginal conditions. Combination of this bioresponsive hydrogel with liquified human semen at a volumetric ratio of 1:5 dramatically reduces in vitro sperm migration by 97%. Simultaneously, total sperm motility decreases from 72.0 ± 9.9% to 7.9 ± 13.7%, which is significantly below the WHO criteria defined for male fertility. Safety assessments performed in vitro and in vivo underline a robust vaginal safety profile comparable to approved vaginal products. Moreover, the results from an exploratory animal study performed with female New Zealand White rabbits suggest that the drug-free physical barrier established intravaginally after exposure of the bioresponsive CP4%/PVP4% hydrogel to alkaline semen seems at least equivalent in the prevention of pregnancy in vivo to the VCF® Gel (Apothecus Pharmaceuticals, Ronkonkoma, NY, USA), a marketed spermicidal on-demand product containing nonoxynol-9.