title: Nanoparticles Encapsulated with LL37 and Serpin A1 Promotes Wound Healing and Synergistically Enhances Antibacterial Activity.
abstract: Wound care is a serious healthcare concern, often complicated by prolonged inflammation and bacterial infection, which contributes significantly to mortality and morbidity. Agents commonly used to treat chronic wound infections are limited due to toxicity of the therapy, multifactorial etiology of chronic wounds, deep skin infections, lack of sustained controlled delivery of drugs, and development of drug resistance. LL37 is an endogenous host defense peptide possessing antimicrobial activity and is involved in the modulation of wound healing. Serpin A1 (A1) is an elastase inhibitor and has been shown to demonstrate wound-healing properties. Hence, our goal was to develop a topical combination nanomedicine for the controlled sustained delivery of LL37 and A1 at precise synergistic ratio combinations that will significantly promote wound closure, reduce bacterial contamination, and enhance anti-inflammatory activity. We have successfully developed the first solid lipid nanoparticle (SLN) formulation that can simultaneously deliver LL37 and A1 at specific ratios resulting in accelerated wound healing by promoting wound closure in BJ fibroblast cells and keratinocytes as well as synergistically enhancing antibacterial activity against S. aureus and E. coli in comparison to LL37 or A1 alone.
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, College of Pharmacy, Faculty of Health Sciences, University of Manitoba , 750 McDermot Avenue, Winnipeg, Manitoba R3E 0T5, Canada.
authors.forename: Miral
authors.initials: M
authors.lastname: Fumakia
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, College of Pharmacy, Faculty of Health Sciences, University of Manitoba , 750 McDermot Avenue, Winnipeg, Manitoba R3E 0T5, Canada.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Ho
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D001424:Bacterial Infections / Q000188:drug therapy; D054804:Cathelicidins / Q000737:chemistry*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits; D012867:Skin / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*; D000515:alpha 1-Antitrypsin / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D054804:Cathelicidins; D008055:Lipids; D000515:alpha 1-Antitrypsin
keywords: LL37; anti-inflammatory; antibacterial; chronic wounds; combination nanomedicine; drug delivery; serpin A1; solid lipid nanoparticles; synergy; wound healing