Alpha-tocopheryl succinate improves encapsulation, pH-sensitivity, antitumor activity and reduces toxicity of doxorubicin-loaded liposomes
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Universidade Federal de Minas Gerais
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Artigo de periódico
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Membros da banca
Resumo
Doxorubicin (DOX) plays an important role in cancer treatment; however, high cardiotoxicity and low penetration in solid tumors are the main limitations of its use. Liposomal formulations have been developed to attenuate the DOX toxicity, but the technological enhancement of the liposomal formulation as well as the addition of another agent with antitumor properties, like alpha-tocopheryl succinate (TS), a semi-synthetic analog of vitamin E, could certainly bring benefits. Thus, in this study, it was proposed the development of liposomes composed of DOX and TS (pHSL-TS-DOX). A new DOX encapsulation method, without using the classic ammonium sulfate gradient with high encapsulation percentage was developed. Analysis of Small Angle X-ray Scattering (SAXS) and release study proved the pH-sensitivity of the developed formulation. It was observed stabilization of tumor growth using pHSL-TS-DOX when compared to free DOX. The toxicity tests showed the safety of this formulation since it allowed body weight initial recovery after the treatment and harmless to heart and liver, main target organs of DOX toxicity. The developed formulation also avoided the occurrence of myelosuppression, a typical adverse effect of DOX. Therefore, pHSL-TS-DOX is a promising alternative for the treatment of breast cancer since it has adequate antitumor activity and a safe toxicity profile.
Abstract
Assunto
Câncer de mama, Agentes antineoplásicos
Palavras-chave
Breast cancer, Doxorubicin, Alpha-tocopheryl succinate, Antitumor activity, Cytotoxicity, PH-sensitivity
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Endereço externo
https://www.sciencedirect.com/science/article/pii/S0928098719304786