Tacrolimus delivered from polymeric implants suppressed inflammation and angiogenesis in vivo without inducing nephrotoxicity, hepatotoxicity, and myelosuppression.

Resumo
Implants containing tacrolimus and poly(ɛ-caprolactone) (tacrolimus PCL implants) were designed to release the drug directly into the inflammatory and angiogenesis site without inducing systemic toxicity. A non-biocompatible sponge, inserted into the subcutaneous tissue of mice, functioned as a frame for inducing inflammatory and angiogenic responses. After 4 days post-insertion of sponges, PCL implants loaded with tacrolimus were inserted adjacent to the pathological site, and the cellular and molecular components of inflammation were monitored. PCL implants constantly released tacrolimus into the target site. Tacrolimus limited the expression of TNF-α, a pro-angiogenic and pro-inflammatory cytokine. As a result, the neovascularization was inhibited. It also limited the neutrophil migration at the early stage of inflammation and the monocyte/macrophage infiltration at the proliferative phase due to the reduced activities of myeloperoxidase (MPO) and N-Acetyl-β-D-Glucosaminidase (NAG), respectively. Tacrolimus released from PCL implants did not induce toxicity in the liver and kidney, since the biomarkers of functionality of these organs showed normal levels. In addition, the drug did not promote myelosuppression. It was suggested that the controlled tacrolimus release from implantable devices directly into the pathological site could provide the remission of the inflammatory and angiogenic responses without carrying out organ toxicity.
Descrição
Palavras-chave
Polymeric implants, Local drug delivery systems, Murine sponge model, Inflammatory angiogenesis
Citação
OLIVEIRA, L. G. de et al. Tacrolimus delivered from polymeric implants suppressed inflammation and angiogenesis in vivo without inducing nephrotoxicity, hepatotoxicity, and myelosuppression. Journal of Drug Delivery Science and Technology, v. 43, p. 487-495, 2018. Disponível em: <https://www.sciencedirect.com/science/article/pii/S1773224717304264>. Acesso em: 05 abr. 2018.