(M0930-05-27) Non-woven Polymeric Fiber Mats for Female-Initiated On-Demand Contraception Without Hormones

Purpose: To provide women with more choices for preventing pregnancy without the use of hormones, this research explores an innovative, drug-free bioengineering concept that offers the convenience of a female-initiated prevention technology suitable for on-demand contraception. Although barrier devices such as the female condom and diaphragm reduce the risk of unintended pregnancy most effectively, low user acceptability and high cost have constrained widespread use of these devices. Alternatively, women can select a vaginal spermicide such as nonxynol-9 or the acidic buffer gel composition Phexxi^® as a hormone-free vaginal product to prevent unwanted pregnancy. The reported failure rate of up to 25% in preventing pregnancy renders these marketed on-demand products among the least effective of all modern family planning methods. Moreover, nonxynol-9 is suspected to alter the vaginal microflora and induce immunoinflammatory reactions at the cervicovaginal mucosa, thereby increasing the risk for acute and recurring vaginal infections, including sexually transmissible infections such as HIV/AIDS. Collectively, these results establish the urgent need for novel nonsteroidal contraceptive products that are female-initiated and act prior to fertilization.

Methods: Non-woven fiber mats comprised of equal amounts of Carbopol^® 974P (CP) and polyvinylpyrrolidone (PVP) were fabricated using single nozzle electrospinning. Combination of these polymeric fiber mats with vaginal fluid simulant, pH 4.2, (VFS) and seminal fluid simulant, pH 7.7, (SFS) established a bioresponsive gel phase, which exhibited different viscoelastic properties that were quantified using the TA-XTPlus Texture Analyzer. In parallel, buffer capacity of the gel phase was measured using the DeltaTrak^® ISFET pH probe. Compatibility of non-woven polymeric fiber mats with the physiologically-important homeostasis between vaginal microbiota and mucosal environment was examined using an immune-competent, human-derived ex vivo model comprised of cervicovaginal Vk2/E6E7 cells co-cultured with Lactobacillus crispatus. After a 24-hr incubation period, epithelial viability was assessed using the MTT assay, the number of viable bacteria was determined using conventional colony count, and release of the proinflammatory biomarker IL-1α was quantified using ELISA. To assess contraceptive efficacy of non-woven CP/PVP fiber mats after exposure to liquified human semen, sperm number and motility were quantified microscopically using the Makler™ counting chamber. 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: Exposure of non-woven CP/PVP fiber mats to acidic VFS rapidly enabled conversion of the fabric-like polymer material into a viscous hydrogel exhibiting a pH value of 3.8. In the presence of alkaline SFS, viscoelastic gel properties significantly increased resulting in a 92.3% greater work of shear that was required to spread the CP/PVP gel phase at a 1:1 volumetric dilution with SFS (5.27±0.10 N×s vs. 2.74±0.03 N×s). In parallel, however, the gel phase pH value remained acidic rising from 3.8 to 4.7±0.1 only. When compared to media control, normal growth pattern of Lactobacillus crispatus co-cultured with human cervicovaginal cells was maintained in the presence of non-woven CP/PVP fiber mats. Similarly, incubation of this immune-competent, human-derived ex vivo model with non-woven CP/PVP fiber mats did not significantly increase release of the proinflammatory biomarker IL-1α and maintained vaginal cell viability. In contrast, CP/PVP fiber mats established a significant contraceptive barrier in the presence of a 12-fold greater volume fraction of liquified human semen that dramatically reduced the total number of sperm cells traversing the gel phase by ~95%. Simultaneously, total motility of sperm cells capable of moving across the CP/PVP gel barrier decreased from 73.8±10.2% to 8.0±13.8%.

Conclusion: Single nozzle electrospinning is an effective technology to fabricate non-woven CP/PVP fiber mats that rapidly establish a bioresponsive gel phase upon exposure to acidic vaginal fluid, which dramatically increases in viscoelastic properties when combined with alkaline seminal fluid. Non-woven CP/PVP fiber mats demonstrate a robust vaginal safety profile with favorable vaginal microbiota-host interactions. In the presence of liquified human semen, the gel phase established from non-woven CP/PVP fiber mats represents a drug-free physical and chemical barrier that effectively reduces sperm motility to levels consistent with infertility.