De Soricellis Chiara, Laigle Chloé, Spinelli Lucio, Monti Maria Chiara, Amante Chiara, Russo Paola, Aquino Rita Patrizia, Rousselle Patricia, Lollo Giovanna, Del Gaudio Pasquale
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy.
Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR CNRS 5305, Université Lyon 1, 69367 Lyon, France.
Int J Pharm. 2025 May 30;677:125668. doi: 10.1016/j.ijpharm.2025.125668. Epub 2025 Apr 30.
Antimicrobial peptides (AMPs) such as LL37 offer a promising alternative to conventional antibiotics in treating chronic and multidrug-resistant wound infections. However, their clinical translation is limited by rapid degradation and cytotoxicity at high concentrations. This study investigates the encapsulation of a palmitoylated LL37 in a FDA-approved poly(lactic-co-glycolic acid) (PLGA) nanoparticles using two fabrication techniques, nanoprecipitation and microfluidics, to enhance stability and controlled peptide release. Microfluidic-generated nanoparticles demonstrated superior size uniformity, smaller hydrodynamic size (102.3 ± 2.0 nm vs 189.3 ± 3.4 nm), improved stability, and prolonged LL37(P) release compared to nanoparticles obtained via bulk nanoprecipitation method. LL37-encapsulated nanoparticles demonstrated controlled peptide release, enhanced keratinocyte uptake, and significant fibroblast-mediated wound closure acceleration. Proteomic analysis of the nanoparticle-protein corona revealed enrichment in proteins involved in coagulation, inflammation modulation, and extracellular matrix remodelling, suggesting an active role of nanoparticles in modulating the wound healing microenvironment. These findings highlight PLGA-based LL37 loaded nanocarriers as a promising biopolymer platform for AMP delivery in wound healing applications and as a viable therapeutic strategy in regenerative medicine and infection control.
抗菌肽（如LL37）在治疗慢性和多重耐药伤口感染方面为传统抗生素提供了一种有前景的替代方案。然而，它们的临床应用受到快速降解和高浓度时细胞毒性的限制。本研究使用两种制备技术，即纳米沉淀法和微流控法，研究了棕榈酰化LL37在FDA批准的聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒中的包封，以提高稳定性并实现肽的可控释放。与通过批量纳米沉淀法获得的纳米颗粒相比，微流控生成的纳米颗粒表现出更优异的尺寸均匀性、更小的流体动力学尺寸（102.3±2.0纳米对189.3±3.4纳米）、更好的稳定性以及延长的LL37（P）释放。包封LL37的纳米颗粒表现出可控的肽释放、增强的角质形成细胞摄取以及显著加速成纤维细胞介导的伤口闭合。对纳米颗粒-蛋白质冠层的蛋白质组学分析揭示了参与凝血、炎症调节和细胞外基质重塑的蛋白质富集，表明纳米颗粒在调节伤口愈合微环境中发挥着积极作用。这些发现突出了基于PLGA的负载LL37的纳米载体作为伤口愈合应用中抗菌肽递送的有前景的生物聚合物平台，以及作为再生医学和感染控制中可行的治疗策略。
