Alpha-tocopheryl succinate and doxorubicin-loaded liposomes improve drug uptake and tumor accumulation in a murine breast tumor model
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Universidade Federal de Minas Gerais
Descrição
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Artigo de periódico
Título alternativo
Primeiro orientador
Membros da banca
Resumo
Liposomes composed of a rigid bilayer have high plasma stability; however, they can be challenged in efficacy due to complications in releasing the encapsulated drug as well as being internalized by the tumor cell. On the other hand, fusogenic liposomes may fuse with the plasmatic membrane and release encapsulated material directly into the cytoplasm. In a previous study, fusogenic liposomes composed of alpha-tocopheryl succinate (TS) and doxorubicin (DOX) were developed (pHSL-TS-DOX). These stabilized tumor growth and reduced toxicity compared to a commercial formulation. In the present study, we investigated whether cellular uptake or
DOX accumulation in the tumor could justify the better performance of the pHSL-TS-DOX formulation. Release, deformability, and DOX plasmatic concentration studies were also carried out. pHSL-TS-DOX showed an adequate release profile and demonstrated characteristics of a deformable formulation. Data from apoptosis, cell cycle, and nuclear morphology studies have shown that the induction of cell death caused by pHSL-TS-DOX occurred more quickly. Higher DOX cellular uptake and tumor accumulation were observed when pHSL-TSDOX was administered, demonstrating better drug delivery capacity. Therefore, better DOX uptake as well as
tumor accumulation explain the great antitumor activity previously demonstrated for this formulation.
Abstract
Assunto
Câncer, Tumores, Biologia celular e molecular
Palavras-chave
Doxorubicin, Alpha-tocopheryl succinate, PH-sensitive liposomes, Tumor accumulation, Breast cancer
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Curso
Endereço externo
https://www.sciencedirect.com/science/article/pii/S0753332223008247