Lipoxin A.sub.4 encapsulated in PLGA microparticles accelerates wound healing of skin ulcers

Lipoxin A.sub.4 (LXA.sub.4) is involved in the resolution of inflammation and wound healing; however, it is extremely unstable. Thus, to preserve its biological activities and confer stability, we encapsulated LXA.sub.4 in poly-lactic-co-glycolic acid (PLGA) microparticles (LXA.sub.4 -MS) and assess...

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Bibliographic Details
Published in:PloS one 2017-07, Vol.12 (7), p.e0182381
Main Authors: Reis, Mouzarllem Barros, Pereira, Priscilla Aparecida Tartari, Caetano, Guilherme Ferreira, Leite, Marcel Nani, Galvão, Alyne Fávero, Paula-Silva, Francisco Wanderley Garcia, Frade, Marco Andrey Cipriani, Faccioli, Lúcia Helena
Format: Article
Language:English
Subjects:
Acronyms
Health aspects
Physiological aspects
Skin ulcer
Wound healing
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Summary:Lipoxin A.sub.4 (LXA.sub.4) is involved in the resolution of inflammation and wound healing; however, it is extremely unstable. Thus, to preserve its biological activities and confer stability, we encapsulated LXA.sub.4 in poly-lactic-co-glycolic acid (PLGA) microparticles (LXA.sub.4 -MS) and assessed its application in treating dorsal rat skin lesions. Ulcers were sealed with fibrin adhesive and treated with either LXA.sub.4 -MS, unloaded microparticles (Un-MS), soluble LXA.sub.4, or PBS/glue (vehicle). All groups were compared at 0, 2, 7, and 14 days post-lesions. Our results revealed that LXA.sub.4 -MS accelerated wound healing from day 7 and reduced initial ulcer diameters by 80%. Soluble LXA.sub.4, Un-MS, or PBS closed wounds by 60%, 45%, and 39%, respectively. LXA.sub.4 -MS reduced IL-1[beta] and TNF-[alpha], but increased TGF-[beta], collagen deposition, and the number of blood vessels. Compared to other treatments, LXA.sub.4 -MS reduced inflammatory cell numbers, myeloperoxidase (MPO) concentration, and metalloproteinase-8 (MMP8) mRNA in scar tissue, indicating decreased neutrophil chemotaxis. In addition, LXA.sub.4 -MS treatment increased macrophages and IL-4, suggesting a positive impact on wound healing. Finally, we demonstrated that WRW4, a selective LXA.sub.4 receptor (ALX) antagonist, reversed healing by 50%, indicating that LXA.sub.4 must interact with ALX to induce wound healing. Our results show that LXA.sub.4 -MS could be used as a pharmaceutical formulation for the treatment of skin ulcers.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0182381