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bioRxiv · 10.1101/2025.08.14.670442

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

Doud, J. M.·Geib, M. T.·Politch, J. A.·Whaley, K.·Anderson, D. J.·Marathe, J. G.
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Abstract

Study QuestionCan personal lubricants effectively deliver the sperm-agglutinating Human Contraception Antibody (HCA) to achieve on-demand male contraception? Summary AnswerThis 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 AlreadyThe 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, DurationWe 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, MethodsFourteen 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(R)). 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 ChanceAll selected lubricants were nontoxic and did not affect HCAs 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 {micro}g/mL of HCA, the commercial silicone lubricant 11 {+/-} 5.2 {micro}g/mL, and the KY-DE emulsion 27.4 {+/-} 22.4 {micro}g/mL. Futhermore, the formulations did not compromise tissue integrity or viability, or induce significant inflammatory responses. Large Scale DataNot applicable. Limitations, Reasons for CautionWhile 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 FindingsThis 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 Interest(s)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.

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Doud, J. M., Geib, M. T., Politch, J. A., Whaley, K., Anderson, D. J., Marathe, J. G.. 2025-08-20. Revolutionizing male contraception: Personal lubricants as a novel way to deliver the Human Contraception Antibody. https://doi.org/10.1101/2025.08.14.670442

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