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革新男性避孕方法:个人润滑剂作为递送人类避孕抗体的新途径。

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

作者信息

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

机构信息

Department of Medicine, Boston University Aram V. Chobanian & Edward Avedisian School of Medicine, Boston, MA, USA 02118.

Division of Material Science and Engineering, Boston University College of Engineering, Boston, MA, USA 02215.

出版信息

bioRxiv. 2025 Aug 20:2025.08.14.670442. doi: 10.1101/2025.08.14.670442.

Abstract

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.

摘要

研究问题

个人润滑剂能否有效递送精子凝集性人避孕抗体(HCA)以实现按需男性避孕?

总结答案

本研究表明,几种水性润滑剂可有效递送具有生物活性的HCA,且含二甲基硅氧烷的硅酮润滑剂可被改性为适合抗体递送的稳定乳液。

已知信息

基于HCA的阴道膜ZB - 06在女性避孕的I期临床试验中显示出安全有效。男性避孕选择仍然有限。使用性润滑剂作为HCA的递送平台代表了一种新颖且实用的男性避孕方法。

研究设计、规模、持续时间:我们在多种市售性润滑剂中测试了HCA长达两年的稳定性,并使用模拟性交模型测试了其从阴茎装置的递送情况。

参与者/材料、设置、方法:最初对14种商业润滑剂进行筛选,以评估其对精子活力和生存能力的影响、与HCA溶液的混溶性以及HCA活性的保存情况(精子凝集试验)。从中选择了三种水性润滑剂和一种硅酮基润滑剂进行进一步研究。通过加入6% w/w聚乙二醇 - 10二甲基硅氧烷和0.005% v/v吐温 - 20以整合HCA,将硅酮基产品设计成一种新型乳液(KY - DE)。使用动态精子凝集试验和毛细管精子穿透试验,测试制剂随时间的HCA功能稳定性和避孕效果。使用3D打印的阴茎装置和阴道模拟器(Fleshlight)开发了一种新型模拟性交模型。将含HCA的润滑剂应用于“阴茎”,并通过酶联免疫吸附测定(ELISA)和精子凝集试验测量性交过程中递送至“阴道”的HCA浓度。使用阴道组织模型(EpiVaginal,VEC - 100 - FT)进行安全性评估。应用含HCA的润滑剂后,评估生存能力(MTT试验)、紧密连接完整性(跨上皮电阻,TEER)和细胞因子释放情况。

主要结果及机遇的作用

所有选定的润滑剂均无毒,且不影响HCA凝集精子的能力。在毛细管精子穿透试验中,含HCA的润滑剂显著损害精子穿透;在含HCA的润滑剂中,90分钟后很少有活动精子穿透超过1厘米深度,而在大多数未处理的润滑剂中超过80%。重要的是,模拟性交试验证实HCA成功递送至阴道。水性润滑剂平均递送24±8.4μg/mL的HCA,市售硅酮润滑剂为11±5.2μg/mL,KY - DE乳液为27.4±22.4μg/mL。此外,这些制剂未损害组织完整性或生存能力,也未引发显著的炎症反应。

大规模数据

不适用。

局限性、谨慎的原因:虽然这些体外结果支持使用润滑剂作为HCA递送载体的可行性,但转化为临床应用需要进一步验证和临床试验。

研究结果的更广泛影响

这项工作为男性避孕发展提出了一个新方向,利用个人润滑剂的广泛使用引入基于抗体的、可逆的、按需避孕方法。设计一种在不同条件下保持HCA活性并确保更高黏膜递送的硅酮基润滑剂可进一步推进这种方法。

研究资金/利益冲突:这项工作得到了男性避孕倡议的索科尔资助、波士顿大学乔班尼安与阿维迪西安医学院的性医学资助以及美国国立卫生研究院的P50HD096957资助。凯文·惠利(ZabBio)打算将HCA商业化用于避孕。其他作者均无利益冲突。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8301/12393346/df73f9052003/nihpp-2025.08.14.670442v1-f0001.jpg

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