Revolutionizing male contraception: Personal lubricants as a novel way to deliver the Human Contraception Antibody.

STUDY QUESTION: Can personal lubricants effectively deliver the sperm-agglutinating Human Contraception Antibody (HCA) to achieve on-demand male contraception? SUMMARY ANSWER: This study demonstrates that several water-based lubricants can effectively deliver bioactive HCA, and that a dimethicone-containing silicone lubricant can be modified into a stable emulsion suitable for antibody delivery. WHAT IS KNOWN ALREADY: The HCA-based vaginal film ZB-06 was shown to be safe and effective in a Phase I clinical trial for female contraception. Male contraceptive options remain limited. Using sexual lubricants as a delivery platform for HCA represents a novel and practical approach to male contraception. STUDY DESIGN SIZE DURATION: We tested the stability of HCA for up to two years in a variety of commercially available sexual lubricants, and its delivery from a penile device using a simulated intercourse model. PARTICIPANTS/MATERIALS SETTING METHODS: Fourteen commercial lubricants were initially screened for impact on sperm motility and viability, miscibility with HCA solution, and preservation of HCA activity (sperm agglutination test). From these, three water-based and one silicone-based lubricant were selected for further study. The silicone-based product was engineered into a novel emulsion (KY-DE) by incorporating 6% w/w PEG-10 dimethicone and 0.005% v/v TWEEN-20 for HCA integration. Formulations were tested for HCA functional stability and contraceptive efficacy over time using kinetic sperm agglutination assays and a capillary tube sperm penetration test. A novel simulated intercourse model was developed using a 3D-printed penile device and a vaginal analog (Fleshlight(®)). HCA-lube was applied to the "penis", and concentrations of HCA delivered to the "vagina" during intercourse were measured by ELISA and sperm agglutination assay. Safety evaluations were conducted using a vaginal tissue model (EpiVaginal, VEC-100-FT). Viability (MTT assay), tight junction integrity (TEER), and cytokine release were assessed after application of HCA-lube. MAIN RESULTS AND THE ROLE OF CHANCE: All selected lubricants were nontoxic and did not affect HCA's ability to agglutinate sperm. In the capillary tube sperm penetration assay, HCA-formulated lubricants significantly impaired sperm penetration; few motile sperm penetrated past a depth of 1 cm after 90 minutes in the HCA-lubricants vs >80_in most of the untreated lubricants. Importantly, the simulated intercourse assay confirmed successful delivery of HCA to the vagina. Water-based lubricants delivered an average of 24 ± 8.4 μg/mL of HCA, the commercial silicone lubricant 11 ± 5.2 μg/mL, and the KY-DE emulsion 27.4 ± 22.4 μg/mL. Futhermore, the formulations did not compromise tissue integrity or viability, or induce significant inflammatory responses. LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: While these in vitro results support the feasibility of using lubricants as HCA delivery vehicles, translation into clinical application requires further validation and clinical trials. WIDER IMPLICATIONS OF THE FINDINGS: This work presents a new direction in male contraceptive development, leveraging the widespread use of personal lubricants to introduce antibody-based, reversible, on-demand contraception. Engineering a silicone-based lubricant that retains HCA activity under varied conditions and ensures higher mucosal delivery could further advance this approach. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a Sokol Grant from the Male Contraceptive Initiative, a Sexual Medicine Grant from Boston University Chobanian & Avedisian School of Medicine, and grant P50HD096957 from the National Institutes of Health. Kevin Whaley (ZabBio) intends to commercialize HCA for contraception. None of the other authors have competing interests.