Nonoxynol-9 and LL-37 combination synergistically boosts spermicidal activity and reduces irritation

Effective and safe barrier contraception remains a global health priority, particularly concerning sexually transmitted infections (STIs). Nonoxynol-9 (N-9) is a widely used spermicide, but its safety profile and efficacy have been controversial, often causing irritation and potentially increasing STI susceptibility. LL-37, a human antimicrobial peptide, has emerged as a promising candidate for novel spermicides due to its broad-spectrum antimicrobial and potential spermicidal properties. The current research addresses the critical need to enhance spermicidal efficacy and reduce local irritation associated with existing compounds like N-9, by exploring synergistic combinations with safer alternatives like LL-37.

Researchers investigated the combined effects of Nonoxynol-9 and LL-37 on spermicidal activity, irritation, and antimicrobial properties. Processed human sperm, isolated via density gradient centrifugation, were treated with Nonoxynol-9, LL-37, or their combination at various doses. Key spermicidal endpoints included acrosome reaction, DNA fragmentation, and hemizona binding capacity. Antimicrobial activity was assessed by measuring minimal inhibitory concentrations (MICs) against E.coli. In vivo safety was evaluated through mouse experiments, specifically examining skin and vaginal irritation, including epidermal hyperplasia.

The combination of Nonoxynol-9 and LL-37 demonstrated significantly enhanced spermicidal activity. Both compounds individually showed dose-dependent spermicidal effects. Premature acrosome reactions increased by around 9% in the Nonoxynol-9 group and 21% in the LL-37 group. Notably, the combined group exhibited a synergistic effect, raising acrosome-reacted sperm by over 60%. While individual treatments showed no significant changes in DNA fragmentation, the combined group resulted in a 3% increase at a significant level. Regarding sperm binding, Nonoxynol-9 and LL-37 reduced hemizona binding indexes to 43.2 and 8.0, respectively, but the combined group achieved the lowest capacity at 5.6. In mouse models, the addition of LL-37 to Nonoxynol-9 alleviated irritation, reducing skin epidermal hyperplasia and vaginal irritation caused by Nonoxynol-9. > However, the presence of Nonoxynol-9 was found to reduce the antibacterial activity of LL-37, indicating a trade-off in its broad-spectrum protective potential.