Tacrolimus delivered from polymeric implants suppressed inflammation and angiogenesis in vivo without inducing nephrotoxicity, hepatotoxicity, and myelosuppression.
No Thumbnail Available
Date
2018
Journal Title
Journal ISSN
Volume Title
Publisher
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.
Description
Keywords
Polymeric implants, Local drug delivery systems, Murine sponge model, Inflammatory angiogenesis
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.