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

Yajuan Su, Hongjun Wang, Biswajit Mishra, Jayaram Lakshmaiah Narayana, Jiang Jiang, Debra A. Reilly, Ronald R. Hollins, Mark A. Carlson, Guangshun Wang, Jingwei Xie

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2011-2020
Number of pages10
JournalMolecular Pharmaceutics
Volume16
Issue number5
DOIs
StatePublished - May 6 2019

Fingerprint

Nanofibers
Bandages
Biofilms
Peptides
Wounds and Injuries
UCON 50-HB-5100
Debridement
Methicillin-Resistant Staphylococcus aureus
Bacteria
Poloxamer
Acinetobacter baumannii
Klebsiella pneumoniae
CAP18 lipopolysaccharide-binding protein
Monocytes
Skin

Keywords

  • antimicrobial peptides
  • biofilms
  • chronic wounds
  • electrospinning
  • nanofibers
  • topical delivery

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Nanofiber Dressings Topically Delivering Molecularly Engineered Human Cathelicidin Peptides for the Treatment of Biofilms in Chronic Wounds. / Su, Yajuan; Wang, Hongjun; Mishra, Biswajit; Lakshmaiah Narayana, Jayaram; Jiang, Jiang; Reilly, Debra A.; Hollins, Ronald R.; Carlson, Mark A.; Wang, Guangshun; Xie, Jingwei.

In: Molecular Pharmaceutics, Vol. 16, No. 5, 06.05.2019, p. 2011-2020.

Research output: Contribution to journalArticle

@article{009fae1ceabf4c6ba726c66238b48163,
title = "Nanofiber Dressings Topically Delivering Molecularly Engineered Human Cathelicidin Peptides for the Treatment of Biofilms in Chronic Wounds",
abstract = "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.",
keywords = "antimicrobial peptides, biofilms, chronic wounds, electrospinning, nanofibers, topical delivery",
author = "Yajuan Su and Hongjun Wang and Biswajit Mishra and {Lakshmaiah Narayana}, Jayaram and Jiang Jiang and Reilly, {Debra A.} and Hollins, {Ronald R.} and Carlson, {Mark A.} and Guangshun Wang and Jingwei Xie",
year = "2019",
month = "5",
day = "6",
doi = "10.1021/acs.molpharmaceut.8b01345",
language = "English (US)",
volume = "16",
pages = "2011--2020",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Nanofiber Dressings Topically Delivering Molecularly Engineered Human Cathelicidin Peptides for the Treatment of Biofilms in Chronic Wounds

AU - Su, Yajuan

AU - Wang, Hongjun

AU - Mishra, Biswajit

AU - Lakshmaiah Narayana, Jayaram

AU - Jiang, Jiang

AU - Reilly, Debra A.

AU - Hollins, Ronald R.

AU - Carlson, Mark A.

AU - Wang, Guangshun

AU - Xie, Jingwei

PY - 2019/5/6

Y1 - 2019/5/6

N2 - 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.

AB - 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.

KW - antimicrobial peptides

KW - biofilms

KW - chronic wounds

KW - electrospinning

KW - nanofibers

KW - topical delivery

UR - http://www.scopus.com/inward/record.url?scp=85064822634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064822634&partnerID=8YFLogxK

U2 - 10.1021/acs.molpharmaceut.8b01345

DO - 10.1021/acs.molpharmaceut.8b01345

M3 - Article

C2 - 30916573

AN - SCOPUS:85064822634

VL - 16

SP - 2011

EP - 2020

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 5

ER -