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: Itxaso Garcia-Orue, Garazi Gainza, Cecilia Girbau, Rodrigo Alonso, José Javier Aguirre, José Luis Pedraz, Manoli Igartua, Rosa Maria Hernandez
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 108 Pg. 310-316 (Nov 2016) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 27080206 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Infective Agents
• Antimicrobial Cationic Peptides
• Cathelicidins
• Drug Carriers
• Lipids

Topics

• Administration, Topical
• Animals
• Anti-Infective Agents (chemistry)
• Antimicrobial Cationic Peptides
• Cathelicidins (chemistry)
• Cell Movement
• Cell Proliferation
• Cell Survival
• Drug Carriers (chemistry)
• Epithelial Cells (cytology)
• Escherichia coli (drug effects)
• Fibroblasts (metabolism)
• Humans
• Immune System
• Inflammation
• Lipids (chemistry)
• Macrophages (cytology)
• Male
• Mice
• Microbial Sensitivity Tests
• Nanostructures (chemistry)
• RAW 264.7 Cells
• Wound Healing
• Wounds and Injuries (drug therapy)