Nanofiber Dressings Topically Delivering Molecularly Engineered Human Cathelicidin Peptides for the Treatment of Biofilms in Chronic Wounds

• Published in: Molecular pharmaceutics Vol. 16; no. 5; pp. 2011 - 2020
• Main Authors: Su, Yajuan, Wang, Hongjun, Mishra, Biswajit, Lakshmaiah Narayana, Jayaram, Jiang, Jiang, Reilly, Debra A, Hollins, Ronald R, Carlson, Mark A, Wang, Guangshun, Xie, Jingwei
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 06.05.2019
• Subjects: Administration, Cutaneous; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Bandages; Biofilms - drug effects; Cell Survival - drug effects; Diabetes Mellitus, Experimental - complications; Disease Models, Animal; Drug Delivery Systems - methods; Drug Liberation; Humans; Methicillin-Resistant Staphylococcus aureus - drug effects; Mice; Nanofibers - administration & dosage; Nanofibers - chemistry; Poloxamer - chemistry; Polyesters - chemistry; Protein Engineering; Skin - drug effects; Skin - microbiology; Wound Infection - drug therapy; Wound Infection - pathology; topical delivery; electrospinning; biofilms; nanofibers; antimicrobial peptides; chronic wounds
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.8b01345

Biofilms of multidrug-resistant bacteria in chronic wounds pose a great challenge in wound care. Herein, we report the topical delivery of molecularly engineered antimicrobial peptides using electrospun nanofiber dressings as a carrier for the treatment of biofilms of multidrug-resistant bacteria in diabetic wounds. Molecularly engineered human cathelicidin peptide 17BIPHE2 was successfully encapsulated in the core of pluronic F127/17BIPHE2-PCL core–shell nanofibers. The in vitro release profiles of 17BIPHE2 showed an in initial burst followed by a sustained release over 4 weeks. The peptide nanofiber formulations effectively killed methicillin-resistant Staphylococcus aureus (MRSA) USA300. Similarly, the 17BIPHE2 peptide containing nanofibers could also effectively kill other bacteria including Klebsiella pneumoniae (104 to 106 CFU) and Acinetobacter baumannii (104 to 107 CFU) clinical strains in vitro without showing evident cytotoxicity to skin cells and monocytes. Importantly, 17BIPHE2-containing nanofiber dressings without debridement caused five-magnitude decreases of the MRSA USA300 CFU in a biofilm-containing chronic wound model based on type II diabetic mice. In combination with debridement, 17BIPHE2-containing nanofiber dressings could completely eliminate the biofilms, providing one possible solution to chronic wound treatment. Taken together, the biodegradable nanofiber-based wound dressings developed in this study can be utilized to effectively deliver molecularly engineered peptides to treat biofilm-containing chronic wounds.