Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry, and Biology, Linköping University, 581 83 Linköping, Sweden.
J Mater Chem B. 2024 Oct 17;12(40):10320-10331. doi: 10.1039/d4tb01107d.
Membrane active peptides (MAPs) can provide novel means to trigger the release of liposome encapsulated drugs to improve the efficacy of liposomal drug delivery systems. Design of MAP-based release strategies requires possibilities to carefully tailor the interactions between the peptides and the lipid bilayer. Here we explore the influence of lipid vesicle properties on the function of conjugation-dependent MAPs, specifically focusing on two designed peptides, JR2KC and CKV. Utilizing liposomes with differences in size, lipid composition, and surface charge, we investigated the mechanisms and abilities of the peptides to induce controlled release of encapsulated cargo. Our findings indicate that liposome size modestly affects the structural changes and function of the peptides, with larger vesicles facilitating a minor increase in drug release efficiency due to higher peptide-to-liposome ratios. Notably, the introduction of negatively charged lipids significantly enhanced the release efficiency, predominantly through electrostatic interactions that favor peptide accumulation at the lipid bilayer interface and subsequent membrane disruption. The incorporation of cholesterol and a mix of saturated and unsaturated lipids was shown to alter the vesicle's phase behavior, thus modulating the membrane activity of the peptides. This was particularly evident in the cholesterol-enriched liposomes, where JR2KC induced lipid phase separation, markedly enhancing cargo release. Our results underscore the critical role of lipid vesicle composition in the design of MAP-based drug delivery systems, suggesting that precise tuning of lipid characteristics can significantly influence their performance.
膜活性肽（MAPs）可以提供新的手段来触发脂质体包裹药物的释放，从而提高脂质体药物递送系统的疗效。基于 MAP 的释放策略的设计需要仔细调整肽与脂质双层之间相互作用的可能性。在这里，我们探讨了脂质体性质对缀合依赖性 MAP 功能的影响，特别关注两种设计的肽 JR2KC 和 CKV。我们利用具有不同大小、脂质组成和表面电荷的脂质体，研究了肽诱导包封货物受控释放的机制和能力。我们的研究结果表明，脂质体的大小对肽的结构变化和功能有适度的影响，较大的囊泡由于肽与脂质体的比例较高，可轻微提高药物释放效率。值得注意的是，引入带负电荷的脂质显著提高了释放效率，主要是通过静电相互作用促进肽在脂质双层界面处的积累和随后的膜破坏。胆固醇和饱和与不饱和脂质混合物的掺入被证明会改变囊泡的相行为，从而调节肽的膜活性。这在富含胆固醇的脂质体中尤为明显，JR2KC 诱导脂质相分离，显著增强了货物的释放。我们的研究结果强调了脂质体组成在基于 MAP 的药物递送系统设计中的关键作用，表明对脂质特性的精确调整可以显著影响其性能。
