Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland.
Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
Drug Deliv Transl Res. 2023 Sep;13(9):2407-2423. doi: 10.1007/s13346-023-01332-9. Epub 2023 Mar 24.
Chronic wounds affect millions of people globally. This number is set to rise with the increasing incidence of antimicrobial-resistant bacterial infections, such as methicillin-resistant Staphylococcus aureus (MRSA), which impair the healing of chronic wounds. Lacticin 3147 is a two-peptide chain bacteriocin produced by Lactococcus lactis that is active against S. aureus including MRSA strains. Previously, poor physicochemical properties of the peptides were overcome by the encapsulation of lacticin 3147 into solid lipid nanoparticles. Here, a lacticin 3147 solid lipid nanoparticle gel is proposed as a topical treatment for S. aureus and MRSA wound infections. Initially, lacticin 3147's antimicrobial activity against S. aureus was determined before encapsulation into solid lipid nanoparticles. An optimised gel formulation with the desired physicochemical properties for topical application was developed, and the lacticin-loaded solid lipid nanoparticles and free lacticin 3147 aqueous solution were incorporated into separate gels. The release of lacticin 3147 from both the solid lipid nanoparticle and free lacticin gels was measured where the solid lipid nanoparticle gel exhibited increased activity for a longer period (11 days) compared to the free lacticin gel (9 days). Both gels displayed potent activity ex vivo against S. aureus-infected pig skin with significant bacterial eradication (> 75%) after 1 h. Thus, a long-acting potent lacticin 3147 solid lipid nanoparticle gel with the required physicochemical properties for topical delivery of lacticin 3147 to the skin for the potential treatment of S. aureus-infected chronic wounds was developed.
慢性伤口影响着全球数百万人。随着耐抗生素细菌感染(如耐甲氧西林金黄色葡萄球菌,MRSA)的发病率不断上升,这一数字还将继续上升,MRSA 会影响慢性伤口的愈合。乳链菌肽 3147 是一种由乳球菌产生的双肽链细菌素,对金黄色葡萄球菌包括 MRSA 菌株具有活性。此前,通过将乳链菌肽 3147 包封到固体脂质纳米粒中,克服了肽的较差理化性质。在这里,提出了一种乳链菌肽 3147 固体脂质纳米粒凝胶,作为治疗金黄色葡萄球菌和 MRSA 伤口感染的局部治疗方法。最初,在将乳链菌肽 3147 封装到固体脂质纳米粒之前,确定了其对金黄色葡萄球菌的抗菌活性。开发了一种具有所需理化性质的优化凝胶配方,可用于局部应用,将负载乳链菌肽的固体脂质纳米粒和游离乳链菌肽水溶液分别掺入凝胶中。测量了游离乳链菌肽和固体脂质纳米粒凝胶中乳链菌肽的释放情况,其中固体脂质纳米粒凝胶的活性持续时间更长(11 天),而游离乳链菌肽凝胶(9 天)。两种凝胶在体外对金黄色葡萄球菌感染的猪皮均表现出强大的活性,在 1 小时后,细菌清除率显著(>75%)。因此,开发了一种具有所需理化性质的长效强效乳链菌肽 3147 固体脂质纳米粒凝胶,可将乳链菌肽 3147 递送到皮肤中,用于治疗金黄色葡萄球菌感染的慢性伤口。