(M1030-03-17) Bioresponsive Hydrogel Compositions Designed to Fortify Natural Contraceptive Barrier Properties of the Cervicovaginal Environment in Humans

Purpose: In healthy women, viscoelastic properties of the cervical mucus at the end of the progesterone-dominated luteal phase of the menstrual cycle represent a significant physical barrier for sperm cells to enter the uterus. In addition, the acidic environment of the vaginal cavity dramatically decreases sperm motility and viability. For centuries, women relied on these physiological contraceptive barrier properties to manage pregnancies throughout their reproductive life although the failure rate of this natural family planning method ranges between 20-30%. With the emerging need for expanded choices of non-hormonal contraceptive methods that are female-controlled and suitable for on-demand applications, the focus of this research is to explore drug-free, bioresponsive hydrogel compositions designed to fortify these natural physical and chemical barrier properties of the cervicovaginal environment in humans.

Methods: Bioresponsive hydrogels comprised of Carbopol^® 974P (CP) and polyvinylpyrrolidone (PVP) were prepared by gradually suspending the polymer mixture under stirring in 0.01 N NaOH. Final concentrations of CP ranged from 0.4-4% (w/w) and PVP from 0-40% (w/w), respectively. Fully hydrated gel preparations were used for experiments after an overnight gelation time at room temperature. Viscoelastic gel properties after combination with various volume fractions of seminal fluid simulant, pH 7.7 (SFS) up to 1:5 (v/v) were quantified using the TA-XTPlus Texture Analyzer. In parallel, buffer capacity of the gel phase was measured using the DeltaTrak^® ISFET pH probe. Experiments were performed in triplicate. A statistically significant difference (p < 0.05) between treatment groups was assessed by one-way analysis of variance or two-sided Student’s t test for pairwise comparison.

Results: In the absence of PVP, the work of shear required to spread the acrylic acid-based CP gel after combination with different volume fractions of SFS consistently increases from 3.47±0.03 N×s to a maximum value of 6.37±0.05 N×s at a gel/SFS ratio of 1:5 (v/v). In parallel, the gel pH value increases from 3.15±0.05 to 4.45±0.05. As summarized in Table 1, inclusion of the polar PVP polymer in the gel composition amplifies these bioresponsive changes in viscoelastic properties after combination with alkaline seminal fluid simulant up to 42% as measured for the 4%CP/40%PVP gel. It is noted that incorporation of PVP in the gel composition appears to decrease the acid-buffering capacity of the hydrogel as demonstrated by the consistently rising gel pH value measured after a five-fold dilution with SFS. Interestingly, the presence of PVP significantly alters pH-dependent viscoelastic properties of CP gels that are reported to positively correlate with CP concentration. In contrast, the data in Table 2 demonstrate that CP/PVP gel compositions comprised of lower CP concentrations significantly exceeded the work of shear required to spread the CP/PVP gel composition containing a 10-fold greater CP concentration. The acid-buffering capacity of CP/PVP gels, however, was directly proportional to the CP concentration present in the hydrogel composition.

Conclusion: Drug-free hydrogel compositions comprised of acrylic acid-based CP and the polar PVP polymers demonstrate pH-dependent increases in viscoelastic properties that exceed those measured for the cervical mucus at the end of the progesterone-dominated luteal phase of the menstrual cycle in humans. Further optimization of the CP/PVP composition with a focus on a robust acid-buffering capacity of the bioresponsive hydrogel that maintains the gel pH value below pH 5.5 in the presence of large volume fractions of alkaline seminal fluid will be required for advancing this promising female-controlled, on-demand contraceptive technology designed to fortify natural physical and chemical barrier properties of the cervicovaginal environment towards clinical evaluation.


Table 1: Effect of PVP on Bioresponsive Gel Properties After Combination with Alkaline Seminal Fluid Simulant


Table 2: Effect of CP on Bioresponsive Gel Properties After Combination with Alkaline Seminal Fluid Simulant