title: LL37 loaded nanostructured lipid carriers (NLC): A new strategy for the topical treatment of chronic wounds.
abstract: The LL37 is a human antimicrobial peptide which not only has a broad spectrum of antimicrobial activity, but it has also been proved to modulate wound healing by participating in angiogenesis, epithelial cell migration and proliferation, and immune response. In this work, LL37 has been encapsulated in nanostructured lipid carriers (NLCs), produced by the melt-emulsification method, in order to improve its effectiveness. The characterisation of the NLC-LL37 showed a mean size of 270nm, a zeta potential of -26mV and an encapsulation efficiency of 96.4%. The cytotoxicity assay performed in Human Foreskin Fibroblasts demonstrated that the NLC-LL37 did not affect cell viability. Moreover, the in vitro bioactivityassay evidenced that the peptide remained active after the encapsulation, since the NLC-LL37 reversed the activation of the macrophages induced by LPS in the same way as the LL37 in solution. In addition, the in vitro antimicrobial assay revealed the NLC-LL37 activity against Escherichia coli. The effectiveness of the nanoparticles was assessed in a full thickness wound model indb/dbmice. The data demonstrated that NLC-LL37 significantly improved healing compared to the same concentration of the LL37 solution in terms of wound closure, reepithelisation grade and restoration of the inflammatory process. Overall, these findings suggest a promising potential of the NLC-LL37 formulation for chronic wound healing.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain.
authors.forename: Itxaso
authors.initials: I
authors.lastname: Garcia-Orue
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biopraxis Research AIE, Miñano, Vitoria-Gasteiz, Spain.
authors.forename: Garazi
authors.initials: G
authors.lastname: Gainza
authors.affiliation: Department of Immunology, Microbiology and Parasitology, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Girbau
authors.affiliation: Department of Immunology, Microbiology and Parasitology, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Alonso
authors.affiliation: Hospital Universitario de Álava (HUA) Txagorritxu, Vitoria-Gasteiz 01009, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Aguirre
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain. Electronic address: rosa.hernandez@ehu.es.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Hernandez
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000737:chemistry*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry; D004847:Epithelial Cells / Q000166:cytology; D004926:Escherichia coli / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007249:Inflammation; D008055:Lipids / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D049329:Nanostructures / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D014945:Wound Healing; D014947:Wounds and Injuries / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D004337:Drug Carriers; D008055:Lipids
keywords: Antimicrobial peptide; Chronic wounds; LL37; Lipid nanoparticles; NLC (nanostructured lipid carriers)