Combined Nonoxynol-9 and LL-37 synergistically boosts spermicidal activity while reducing irritation

Current barrier contraceptives often rely on Nonoxynol-9 (N-9) as a spermicide, but its safety and efficacy are controversial, with concerns about vaginal irritation and potential for increased STI transmission. LL-37, an endogenous antimicrobial peptide, has shown promise as an alternative spermicidal agent with potential antimicrobial benefits. The research gap lies in developing a safer, more effective spermicide that combines potent spermicidal action with reduced irritation and potentially enhanced antimicrobial properties, addressing the dual global concerns of birth control and sexually transmitted infections.

Researchers evaluated the spermicidal, antimicrobial, and irritation profiles of Nonoxynol-9, LL-37, and their combination. Processed sperm from density gradient centrifugation were treated with the compounds to assess spermicidal activity, including acrosome reaction, DNA fragmentation, and hemizona binding. Antimicrobial activity was measured against E.coli via minimal inhibitory concentrations. Mouse experiments were conducted to investigate skin and vaginal irritation caused by the individual components and the combined formulation.

Both Nonoxynol-9 and LL-37 exhibited dose-dependent spermicidal activities. Individually, they significantly increased acrosome-reacted sperm by around 9% and 21%, respectively. However, the combined group demonstrated a synergistic effect, raising acrosome-reacted sperm by over 60%. While DNA fragmentation showed no significant changes with individual treatments, the combined group resulted in a 3% increase at a significant level. Hemizona binding indexes, indicating sperm binding capacity, were 43.2 for Nonoxynol-9, 8.0 for LL-37, and lowest at 5.6 for the combination. In animal models, the addition of LL-37 to Nonoxynol-9 alleviated disruptions, reducing skin epidermal hyperplasia and vaginal irritation caused by Nonoxynol-9. > The combined formulation significantly enhanced spermicidal effects and reduced irritation, but the presence of Nonoxynol-9 unfortunately reduced the antimicrobial activity of LL-37.