Improved burn wound healing by the antimicrobial peptide LLKKK18 released from conjugates with dextrin embedded in a Carbopol gel

作者: João P. Silva , Sandeep Dhall , Monika Garcia , Alex Chan , César Costa

DOI: 10.1016/J.ACTBIO.2015.07.043

关键词: AngiogenesisWound healingAntimicrobial peptidesIn vivoMacrophagePharmacologyBiomedical engineeringM2 MacrophageInflammationAntimicrobialMaterials science

摘要: Abstract Antimicrobial peptides (AMPs) are good candidates to treat burn wounds, a major cause of morbidity, impaired life quality and resources consumption in developed countries. We took advantage commercially available hydrogel, Carbopol®, vehicle for topical administration that maintains moist environment within the wound site. hypothesized incorporation LLKKK18 conjugated dextrin would improve healing process rat burns. Whereas hydrogel improves healing, released from conjugates further accelerated closure, simultaneously improving healing. Indeed, release reduced oxidative stress inflammation (low neutrophil macrophage infiltration pro-inflammatory cytokines levels). Importantly, it induced faster resolution inflammatory stage through early M2 recruitment. In addition, stimulated angiogenesis (increased VEGF microvessel development vivo ). Moreover, collagen staining evaluated by Masson’s Trichrome was visually much more intense after treatment with LLKKK18, suggesting higher deposition. Overall, we generated an effective, safe inexpensive formulation wound, easy apply remove, potential prevent infection due presence antimicrobial peptide. These findings propel us study this LLKKK18-containing formulation, setting foundations towards therapeutic approach treatment. Statement Significance This work presents newly holds great as It is based on sustained delivery peptide – dextrin, degradation backbone upon exposure α-amylases. Conjugates were embedded suitable provides wound. obtained efficient, non-expensive apply-and-remove, has first time ability demonstrated its main mechanisms action identified.

参考文章(58)
O Distler, M Kurowska-Stolarska, J H W Distler, A Hirth, Angiogenic and angiostatic factors in the molecular control of angiogenesis. The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine. ,vol. 47, pp. 149- 161 ,(2003)
José Carlos Santos, Sandro Silva‐Gomes, João Pedro Silva, Miguel Gama, Gustavo Rosa, Richard L. Gallo, Rui Appelberg, Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice Immunity, inflammation and disease. ,vol. 2, pp. 1- 12 ,(2014) , 10.1002/IID3.7
W. B. Norbury, M. G. Jeschke, D. N. Herndon, Metabolic changes following major burn injury: How to improve outcome Springer New York. pp. 514- 524 ,(2006) , 10.1007/0-387-35096-9_48
Bruce A. Mast, Gregory S. Schultz, Interactions of cytokines, growth factors, and proteases in acute and chronic wounds Wound Repair and Regeneration. ,vol. 4, pp. 411- 420 ,(1996) , 10.1046/J.1524-475X.1996.40404.X
Arti Parihar, Mordhwaj S. Parihar, Stephen Milner, Satyanarayan Bhat, Oxidative stress and anti-oxidative mobilization in burn injury Burns. ,vol. 34, pp. 6- 17 ,(2008) , 10.1016/J.BURNS.2007.04.009
Abdelhamid Elgawish, Marcus Glomb, Miriam Friedlander, Vincent M. Monnier, Involvement of hydrogen peroxide in collagen cross-linking by high glucose in vitro and in vivo Journal of Biological Chemistry. ,vol. 271, pp. 12964- 12971 ,(1996) , 10.1074/JBC.271.22.12964
Guillaume Chaby, Patricia Senet, Michel Vaneau, Philippe Martel, Jean-Claude Guillaume, Sylvie Meaume, Luc Téot, Clélia Debure, Anne Dompmartin, Hélène Bachelet, Hervé Carsin, Véronique Matz, Jean Louis Richard, Jean Michel Rochet, Nathalie Sales-Aussias, Anne Zagnoli, Catherine Denis, Bernard Guillot, Olivier Chosidow, Dressings for acute and chronic wounds: a systematic review. Archives of Dermatology. ,vol. 143, pp. 1297- 1304 ,(2007) , 10.1001/ARCHDERM.143.10.1297
S. Guo, L.A. DiPietro, Factors Affecting Wound Healing Journal of Dental Research. ,vol. 89, pp. 219- 229 ,(2010) , 10.1177/0022034509359125
I. Nagaoka, K. Kuwahara-Arai, H. Tamura, K. Hiramatsu, M. Hirata, Augmentation of the bactericidal activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by amino acid substitutions. Inflammation Research. ,vol. 54, pp. 66- 73 ,(2005) , 10.1007/S00011-004-1323-8
Denis Okan, Kevin Woo, Elizabeth A. Ayello, Gary Sibbald, The role of moisture balance in wound healing. Advances in Skin & Wound Care. ,vol. 20, pp. 39- 53 ,(2007) , 10.1097/00129334-200701000-00013