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Type:	Artigo de Periódico
Title:	Co-delivery of doxorubicin, docosahexaenoic acid, and -tocopherol succinate by nanostructured lipid carriers has a synergistic effect to enhance antitumor activity and reduce toxicity
Authors:	Eduardo Burgarelli Lages Renata Salgado Fernandes Juliana de Oliveira Silva Ângelo Malachias de Souza Geovanni Dantas Cassali André Luís Branco de Barros Lucas Antônio Miranda Ferreira
Abstract:	Doxorubicin (DOX) is widely used in cancer treatment, however, its use is often limited due to its side effects. To avoid these shortcomings, the encapsulation of DOX into nanocarriers has been suggested. Herein, we proposed a novel nanostructured lipid carrier (NLC) formulation loading DOX, docosahexaenoic acid (DHA), and α-tocopherol succinate (TS) for cancer treatment. DHA is an omega-3 fatty acid and TS is a vitamin E derivative. It has been proposed that these compounds can enhance the antitumor activity of chemotherapeutics. Thus, we hypothesized that the combination of DOX, DHA, and TS in NLC (NLC-DHA-DOX-TS) could increase antitumor efficacy and also reduce toxicity. NLC-DHA-DOX-TS was prepared using emulsification-ultrasound. DOX was incorporated after preparing the NLC, which prevented its degradation during manufacture. High DOX encapsulation efficiency was obtained due to the ion-pairing with TS. This ion-pairing increases lipophilicity of DOX and reduces its crystallinity, contributing to its encapsulation in the lipid matrix. Controlled DOX release from the NLC was observed in vitro, with increased drug release at the acidic environment. In vitro cell studies indicated that DOX, DHA, and TS have synergistic effects against 4T1 tumor cells. The in vivo study showed that NLC-DHA-DOX-TS exhibited the greatest antitumor efficacy by reducing tumor growth in 4T1 tumor-bearing mice. In addition, this formulation reduced mice mortality, prevented lung metastasis, and decreased DOX-induced toxicity to the heart and liver, which was demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that NLC-DHA-DOX-TS may be a promising carrier for breast cancer treatment.
Subject:	Câncer Quimioterápicos Compostos químicos
language:	eng
metadata.dc.publisher.country:	Brasil
Publisher:	Universidade Federal de Minas Gerais
Publisher Initials:	UFMG
metadata.dc.publisher.department:	FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS ICB - DEPARTAMENTO DE PATOLOGIA ICX - DEPARTAMENTO DE FÍSICA
Rights:	Acesso Restrito
metadata.dc.identifier.doi:	https://doi.org/10.1016/j.biopha.2020.110876
URI:	http://hdl.handle.net/1843/51102
Issue Date:	2020
metadata.dc.url.externa:	https://www.sciencedirect.com/science/article/pii/S0753332220310684
metadata.dc.relation.ispartof:	Biomedicine & Pharmacotherapy
Appears in Collections:	Artigo de Periódico

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