Alpha-tocopheryl succinate and doxorubicin-loaded liposomes improve drug uptake and tumor accumulation in a murine breast tumor model
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 relea...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | Brasil |
| Institución: | Universidade Federal de Minas Gerais (UFMG) |
| Repositorio: | Repositório Institucional da UFMG |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.ufmg.br:1843/79648 |
| Acceso en línea: | https://doi.org/10.1016/j.biopha.2023.115034 http://hdl.handle.net/1843/79648 https://orcid.org/0000-0001-6704-4057 https://orcid.org/0000-0002-2912-5312 https://orcid.org/0000-0001-8562-8689 https://orcid.org/0000-0002-8703-4283 https://orcid.org/0000-0001-7979-1156 https://orcid.org/0000-0003-4782-5416 |
| Access Level: | acceso abierto |
| Palabra clave: | Doxorubicin Alpha-tocopheryl succinate PH-sensitive liposomes Tumor accumulation Breast cancer Câncer Tumores Biologia celular e molecular |
| Sumario: | 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. |
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