Z36 - Chitosan-Based Thermoresponsive Hydrogel as a Treatment for Bacterial Vaginosis

Friday, October 10, 2025

10:00 AM - 11:00 AM PDT

Location: Exhibit Hall F, G & H

Presenting Author(s)

Gillian Sebald

Student
UC Riverside
Riverside, California, United States

Co-Author(s)

YL

Yumie Lee, B.S.

Graduate Research Student
UC San Diego
La Jolla, California, United States

Last Author(s)

Erika Cyphert, Ph.D.

Assistant Professor
UC San Diego
San Diego, California, United States

Primary Investigator(s)

Erika Cyphert, Ph.D.

Assistant Professor
UC San Diego
San Diego, California, United States

Introduction: : Bacterial vaginosis (BV) is a common bacterial overgrowth of anaerobic bacteria in the vaginal microbiome that affects approximately 30% of women. In non-BV states, the vaginal microbiome is typically characterized by a dominance of Lactobacillus spp. However, an overgrowth of anaerobic bacteria like Prevotella spp. and G. vaginalis can inhibit lactic acid producing bacteria, Lactobacillus spp., which contributes to abnormal increase in vaginal pH and, consequently, a BV diagnosis. BV increases the risk of preterm birth and pelvic inflammatory disease and is frequently treated with antibiotics, such as metronidazole. However, antibiotic treatment is often insufficient, with more than 50% of cases recurring within six months and frequent doses required [1]. To improve treatment outcomes of BV, we developed a chitosan-based thermoresponsive hydrogel to improve local delivery of therapeutics. By altering the ratio of chitosan, dihydrocaffeic acid (DHCA), and β-glycerophosphate (β-GP), we sought to optimize the formation of a mucoadhesive and thermoresponsive hydrogel to rapidly gel at body temperature. This was done to determine the ideal formulation to maximize the hydrogel’s retention in the vaginal microbiome.

Materials and

Methods: : The hydrogel composition was modified from Liu et al. due to its injectable thermogelling bioadhesive properties [2]. A two step synthesis process was used, where solution one was produced by dissolving low or medium molecular weight chitosan (20 mg/ml) and DHCA (1.5 mg/ml) in either 0.6% or 1% acetic acid (pH 4.3). The solution was mixed vigorously for 40 minutes at room temperature. Using β-GP (0.5 mg/ml) in ultrapure water, solution two was made (Fig. 1A). The optimal composition of the hydrogel that quickly gelled at physiological temperature (37℃) was determined by varying the ratios of solution one and two. Scanning electron microscopy is used to characterize the morphology and rheology is used to evaluate the mucoadhesive properties of the formulations.

Results, Conclusions, and Discussions:: In the resulting hydrogels, increasing the β-GP concentration showed a significant downward trend in gelation time (Fig 1B). When synthesizing using 0.5 g/ml of β-GP exclusively, decreasing the proportion of solution one relative to solution two showed a trend of decreasing gelation time (Fig. 1C). Additionally, medium molecular weight chitosan showed a significantly lower gelation time overall in comparison to low molecular weight chitosan (p = 0.00006) (Fig. 1D). However, this could partially be attributed to the increased viscosity of medium molecular weight chitosan prior to the gel being exposed to physiological conditions.
Medium molecular weight chitosan, when combined with 0.5 g/ml of β-GP, showed improved thermoresponsive properties at 37℃ due to its lower gelation time. However, its increased viscosity upon synthesis could potentially hinder its injectability. Due to this, low molecular weight chitosan may be the preferred option for vaginal administration. Further research is needed focusing on low molecular weight chitosan, using the 6:1 solution one to solution two ratio, to determine the thermoresponsive properties, the morphology, and the mucoadhesive properties to maximize vaginal retention.

Acknowledgements and/or References (Optional): : We would like to thank the Shu Chien-Gene Lay Department of Bioengineering and the UC San Diego Bioengineering Research Experience for Undergraduates Program. G.S.’s participation in the Bioengineering Research Experience for Undergraduates Program was generously supported through funding from the Fronek family.
[1] Ravel J. et al. Microbiome (2013) [2] Liu C, et al. Int J Biol Macromol (2022)