Please use this identifier to cite or link to this item: http://www.repositorio.ufop.br/handle/123456789/9917
Title: Tacrolimus delivered from polymeric implants suppressed inflammation and angiogenesis in vivo without inducing nephrotoxicity, hepatotoxicity, and myelosuppression.
Authors: Oliveira, Leandro Gonzaga de
Miranda, Marina Barcelos de
Moura, Sandra Aparecida Lima de
Silva, Gisele Rodrigues da
Keywords: Polymeric implants
Local drug delivery systems
Murine sponge model
Inflammatory angiogenesis
Issue Date: 2018
Citation: 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.
Abstract: 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.
URI: http://www.repositorio.ufop.br/handle/123456789/9917
metadata.dc.identifier.uri2: https://www.sciencedirect.com/science/article/pii/S1773224717304264
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