{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:31Z","timestamp":1785414451460,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,20]]},"group-title":"Bioengineering","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Male Contraceptive Initiative","award":["Sokol grant"],"award-info":[{"award-number":["Sokol grant"]}]},{"award":["Sexual Medicine Grant"],"award-info":[{"award-number":["Sexual Medicine Grant"]}],"id":[{"id":"https:\/\/ror.org\/03ps5d564","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P50HD096957"],"award-info":[{"award-number":["P50HD096957"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Study Question<\/jats:title>\n                  <jats:p>Can personal lubricants effectively deliver the sperm-agglutinating Human Contraception Antibody (HCA) to achieve on-demand male contraception?<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Summary Answer<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>What Is Known Already<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Study Design, Size, Duration<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Participants\/Materials, Setting, Methods<\/jats:title>\n                  <jats:p>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\u00ae). HCA-lube was applied to the \u201cpenis\u201d, and concentrations of HCA delivered to the \u201cvagina\u201d 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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Main Results and the Role of Chance<\/jats:title>\n                  <jats:p>All selected lubricants were nontoxic and did not affect HCA\u2019s 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 &gt;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 \u00b1 8.4 \u00b5g\/mL of HCA, the commercial silicone lubricant 11 \u00b1 5.2 \u00b5g\/mL, and the KY-DE emulsion 27.4 \u00b1 22.4 \u00b5g\/mL. Futhermore, the formulations did not compromise tissue integrity or viability, or induce significant inflammatory responses.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Large Scale Data<\/jats:title>\n                  <jats:p>Not applicable.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Limitations, Reasons for Caution<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Wider Implications of the Findings<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Study Funding\/Competing Interest(s)<\/jats:title>\n                  <jats:p>This work was supported by a Sokol Grant from the Male Contraceptive Initiative, a Sexual Medicine Grant from Boston University Chobanian &amp; 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.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.14.670442","type":"posted-content","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T19:50:12Z","timestamp":1755719412000},"source":"Crossref","is-referenced-by-count":0,"title":["Revolutionizing male contraception: Personal lubricants as a novel way to deliver the Human Contraception Antibody"],"prefix":"10.64898","author":[{"given":"JM","family":"Doud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MT","family":"Geib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-0135","authenticated-orcid":false,"given":"JA","family":"Politch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3856-6803","authenticated-orcid":false,"given":"K","family":"Whaley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2848-7290","authenticated-orcid":false,"given":"DJ","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-7145","authenticated-orcid":false,"given":"JG","family":"Marathe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025082212200922000_2025.08.14.670442v1.1","unstructured":"UNFPA. 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