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

Autor: Mark A. Carlson, Yajuan Su, Biswajit Mishra, Debra A. Reilly, Ronald R. Hollins, Jiang Jiang, Jayaram Lakshmaiah Narayana, Jingwei Xie, Hongjun Wang, Guangshun Wang
Rok vydání: 2019
Předmět:
Methicillin-Resistant Staphylococcus aureus
Chronic wound
Cell Survival
Polyesters
medicine.medical_treatment
Antimicrobial peptides
Nanofibers
Pharmaceutical Science
Poloxamer
02 engineering and technology
Administration
Cutaneous
Protein Engineering
medicine.disease_cause
030226 pharmacology & pharmacy
Diabetes Mellitus
Experimental
Cathelicidin
Microbiology
Mice
03 medical and health sciences
Wound care
Drug Delivery Systems
0302 clinical medicine
Cathelicidins
Drug Discovery
medicine
Animals
Humans
Skin
Debridement
integumentary system
biology
Chemistry
biochemical phenomena
metabolism
and nutrition
021001 nanoscience & nanotechnology
biology.organism_classification
Bandages
Anti-Bacterial Agents
Acinetobacter baumannii
Disease Models
Animal
Drug Liberation
Staphylococcus aureus
Biofilms
Nanofiber
Wound Infection
Molecular Medicine
medicine.symptom
0210 nano-technology
Antimicrobial Cationic Peptides
Zdroj: Molecular Pharmaceutics. 16:2011-2020
ISSN: 1543-8392
1543-8384
DOI: 10.1021/acs.molpharmaceut.8b01345
Popis: 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.
Databáze: OpenAIRE
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