Zharkova Maria S, Komlev Aleksey S, Filatenkova Tatiana A, Sukhareva Maria S, Vladimirova Elizaveta V, Trulioff Andrey S, Orlov Dmitriy S, Dmitriev Alexander V, Afinogenova Anna G, Spiridonova Anna A, Shamova Olga V
Institute of Experimental Medicine, WCRC "Center for Personalized Medicine", 12 Academic Pavlov Street, St. Petersburg 197022, Russia.
St. Petersburg Pasteur Institute, 14 Mira Street, St. Petersburg 197101, Russia.
Pharmaceutics. 2023 Jan 14;15(1):291. doi: 10.3390/pharmaceutics15010291.
Antimicrobial peptides (AMPs) are acknowledged as a promising template for designing new antimicrobials. At the same time, existing toxicity issues and limitations in their pharmacokinetics make topical application one of the less complicated routes to put AMPs-based therapeutics into actual medical practice. Antiseptics are one of the common components for topical treatment potent against antibiotic-resistant pathogens but often with toxicity limitations of their own. Thus, the interaction of AMPs and antiseptics is an interesting topic that is also less explored than combined action of AMPs and antibiotics. Herein, we analyzed antibacterial, antibiofilm, and cytotoxic activity of combinations of both membranolytic and non-membranolytic AMPs with a number of antiseptic agents. Fractional concentration indices were used as a measure of possible effective concentration reduction achievable due to combined application. Cases of both synergistic and antagonistic interaction with certain antiseptics and surfactants were identified, and trends in the occurrence of these types of interaction were discussed. The data may be of use for AMP-based drug development and suggest that the topic requires further attention for successfully integrating AMPs-based products in the context of complex treatment. AMP/antiseptic combinations show promise for creating topical formulations with improved activity, lowered toxicity, and, presumably, decreased chances of inducing bacterial resistance. However, careful assessment is required to avoid AMP neutralization by certain antiseptic classes in either complex drug design or AMP application alongside other therapeutics/care products.
抗菌肽（AMPs）被认为是设计新型抗菌药物的一个有前景的模板。与此同时，现有的毒性问题及其药代动力学方面的局限性使得局部应用成为将基于AMPs的治疗方法应用于实际医疗实践中相对不那么复杂的途径之一。防腐剂是局部治疗中对抗耐药病原体的常见成分之一，但它们自身往往也存在毒性限制。因此，AMPs与防腐剂的相互作用是一个有趣的话题，而且与AMPs和抗生素的联合作用相比，这方面的研究较少。在此，我们分析了膜溶解型和非膜溶解型AMPs与多种防腐剂组合的抗菌、抗生物膜和细胞毒性活性。分数浓度指数被用作衡量联合应用可能实现的有效浓度降低的指标。确定了与某些防腐剂和表面活性剂存在协同和拮抗相互作用的情况，并讨论了这些类型相互作用发生的趋势。这些数据可能有助于基于AMPs的药物开发，并表明该主题需要进一步关注，以便在复杂治疗背景下成功整合基于AMPs的产品。AMPs/防腐剂组合有望创造出活性提高、毒性降低且可能降低诱导细菌耐药几率的局部制剂。然而，在复杂药物设计或AMPs与其他治疗药物/护理产品同时应用时，需要仔细评估，以避免某些类别的防腐剂使AMPs失活。
