Neff Jennifer A, Bayramov Danir F, Patel Esha A, Miao Jing
Allvivo Vascular, Inc., 20914 Bake Parkway, Suite 100, Lake Forest, CA 92630.
Mil Med. 2020 Jan 7;185(Suppl 1):637-643. doi: 10.1093/milmed/usz222.
Infection frequently complicates the treatment of combat-related wounds, impairs healing, and leads to worse outcomes. To better manage wound infections, antimicrobial therapies that are effective against biofilm and designed for direct wound application are needed. The primary objective of this work was to evaluate a chitosan matrix for delivery of two engineered antimicrobial peptides, (ASP)-1 and ASP-2, to treat biofilm-associated bacteria. A secondary objective was to determine whether replacing the levorotatory (L) form amino acids in ASP-2 with dextrorotatory (D) form amino acids would impact peptide activity.
Chitosan gels loaded with antimicrobial peptides were evaluated for peptide release over 7 days and tested for efficacy against biofilms grown both in vitro on polymer mesh and ex vivo on porcine skin.
When delivered via chitosan, 70% to 80% of peptides were released over 7 days. Gels eradicated biofilms of gram-positive and gram-negative, drug-resistant bacteria in vitro and ex vivo. Under the conditions tested, no meaningful differences in peptide activity between the L and D forms of ASP-2 were detected.
Chitosan serves as an effective delivery platform for ASP-1 and ASP-2 to treat biofilm-embedded bacteria and warrants further development as a topical treatment.
感染常常使与战斗相关伤口的治疗复杂化，损害伤口愈合，并导致更差的结果。为了更好地管理伤口感染，需要对生物膜有效的、设计用于直接伤口应用的抗菌疗法。这项工作的主要目标是评估一种壳聚糖基质，用于递送两种工程抗菌肽（ASP）-1和ASP-2，以治疗与生物膜相关的细菌。次要目标是确定用右旋（D）型氨基酸取代ASP-2中的左旋（L）型氨基酸是否会影响肽的活性。
评估负载抗菌肽的壳聚糖凝胶在7天内的肽释放情况，并测试其对在聚合物网片上体外生长以及在猪皮上体内生长的生物膜的疗效。
通过壳聚糖递送时，70%至80%的肽在7天内释放。凝胶在体外和体内消除了革兰氏阳性和革兰氏阴性耐药菌的生物膜。在所测试的条件下，未检测到ASP-2的L型和D型之间肽活性的显著差异。
壳聚糖作为ASP-1和ASP-2治疗嵌入生物膜细菌的有效递送平台，值得作为局部治疗进一步开发。
