title: PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.
abstract: Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Advanced Drug Delivery and Biomaterials, Avenue E. Mounier 73 box B1.73.12, 1200 Brussels, Belgium.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Chereddy
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Advanced Drug Delivery and Biomaterials, Avenue E. Mounier 73 box B1.73.12, 1200 Brussels, Belgium.
authors.forename: Charles-Henry
authors.initials: CH
authors.lastname: Her
authors.affiliation: Center of Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Michela
authors.initials: M
authors.lastname: Comune
authors.affiliation: Environmental Science and Technology Department, School of Applied Sciences, Cranfield University, Bedford MK43 0AL, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Moia
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Advanced Drug Delivery and Biomaterials, Avenue E. Mounier 73 box B1.73.12, 1200 Brussels, Belgium.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lopes
authors.affiliation: Université catholique de Louvain, Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium.
authors.forename: Paolo E
authors.initials: PE
authors.lastname: Porporato
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Advanced Drug Delivery and Biomaterials, Avenue E. Mounier 73 box B1.73.12, 1200 Brussels, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Vanacker
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, European Medical School at the Carl von Ossietzky University of Oldenburg, Evangelisches Krankenhaus, Steinweg 13-17, 26122 Oldenburg, Germany.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Lam
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, European Medical School at the Carl von Ossietzky University of Oldenburg, Evangelisches Krankenhaus, Steinweg 13-17, 26122 Oldenburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Steinstraesser
authors.affiliation: Université catholique de Louvain, Institut de Recherche Expérimentale et Clinique (IREC), Pole of Pharmacology, Avenue Emmanuel Mounier 52 box B1.53.09, 1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.affiliation: Environmental Science and Technology Department, School of Applied Sciences, Cranfield University, Bedford MK43 0AL, UK.
authors.forename: Huijun
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Center of Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Lino S
authors.initials: LS
authors.lastname: Ferreira
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Advanced Drug Delivery and Biomaterials, Avenue E. Mounier 73 box B1.73.12, 1200 Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute (LDRI), Advanced Drug Delivery and Biomaterials, Avenue E. Mounier 73 box B1.73.12, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000008:administration & dosage* / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006097:Granulation Tissue / Q000187:drug effects; D007249:Inflammation / Q000473:pathology; D015603:Keratinocytes / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
keywords: Host defense peptide; LL37; Lactate; Nanoparticles; Poly(lactic-co-glycolic acid) (PLGA); Wound healing