Co-delivery of doxorubicin, docosahexaenoic acid, and -tocopherol succinate by nanostructured lipid carriers has a synergistic effect to enhance antitumor activity and reduce toxicity

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dc.creatorEduardo Burgarelli Lages
dc.creatorRenata Salgado Fernandes
dc.creatorJuliana de Oliveira Silva
dc.creatorÂngelo Malachias de Souza
dc.creatorGeovanni Dantas Cassali
dc.creatorAndré Luís Branco de Barros
dc.creatorLucas Antônio Miranda Ferreira
dc.date.accessioned2023-03-21T18:51:46Z
dc.date.accessioned2025-09-09T00:19:36Z
dc.date.available2023-03-21T18:51:46Z
dc.date.issued2020
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.identifier.doihttps://doi.org/10.1016/j.biopha.2020.110876
dc.identifier.issn1950-6007
dc.identifier.urihttps://hdl.handle.net/1843/51102
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofBiomedicine & Pharmacotherapy
dc.rightsAcesso Restrito
dc.subjectCâncer
dc.subjectQuimioterápicos
dc.subjectCompostos químicos
dc.subject.otherDoxorubicin
dc.subject.otherCombination therapy
dc.subject.otherIon-pairing
dc.subject.otherSynergism
dc.subject.otherAntitumor activity
dc.subject.otherCardiotoxicity
dc.titleCo-delivery of doxorubicin, docosahexaenoic acid, and -tocopherol succinate by nanostructured lipid carriers has a synergistic effect to enhance antitumor activity and reduce toxicity
dc.typeArtigo de periódico
local.citation.epage12
local.citation.spage1
local.citation.volume132
local.description.resumoDoxorubicin (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.
local.identifier.orcidhttps://orcid.org/0000-0002-2458-6021
local.identifier.orcidhttps://orcid.org/0000-0002-8703-4283
local.identifier.orcidhttps://orcid.org/0000-0002-5650-6743
local.identifier.orcidhttps://orcid.org/0000-0002-7641-6585
local.identifier.orcidhttps://orcid.org/0000-0003-2474-5536
local.publisher.countryBrasil
local.publisher.departmentFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
local.publisher.departmentFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS
local.publisher.departmentICB - DEPARTAMENTO DE PATOLOGIA
local.publisher.departmentICX - DEPARTAMENTO DE FÍSICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0753332220310684

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