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Co-Delivery of an Innovative Organoselenium Compound and Paclitaxel by pH-Responsive PCL Nanoparticles to Synergistically Overcome Multidrug Resistance in Cancer.
Mathes, Daniela; Macedo, Letícia Bueno; Pieta, Taís Baldissera; Maia, Bianca Costa; Rodrigues, Oscar Endrigo Dorneles; Leal, Julliano Guerin; Wendt, Marcelo; Rolim, Clarice Madalena Bueno; Mitjans, Montserrat; Nogueira-Librelotto, Daniele Rubert.
Afiliación
  • Mathes D; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Macedo LB; Laboratório de Testes e Ensaios Farmacêuticos In Vitro, Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Pieta TB; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Maia BC; Laboratório de Engenharia e Processos Químicos, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Rodrigues OED; Laboratório de Testes e Ensaios Farmacêuticos In Vitro, Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Leal JG; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Wendt M; Laboratório de Testes e Ensaios Farmacêuticos In Vitro, Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Rolim CMB; Departamento de Química, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Mitjans M; Departamento de Química, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
  • Nogueira-Librelotto DR; Departamento de Química, Universidade Federal de Santa Maria, Av. Roraima 1000, Santa Maria 97105-900, Brazil.
Pharmaceutics ; 16(5)2024 Apr 26.
Article en En | MEDLINE | ID: mdl-38794252
ABSTRACT
In this study, we designed the association of the organoselenium compound 5'-Seleno-(phenyl)-3'-(ferulic-amido)-thymidine (AFAT-Se), a promising innovative nucleoside analogue, with the antitumor drug paclitaxel, in poly(ε-caprolactone) (PCL)-based nanoparticles (NPs). The nanoprecipitation method was used, adding the lysine-based surfactant, 77KS, as a pH-responsive adjuvant. The physicochemical properties presented by the proposed NPs were consistent with expectations. The co-nanoencapsulation of the bioactive compounds maintained the antioxidant activity of the association and evidenced greater antiproliferative activity in the resistant/MDR tumor cell line NCI/ADR-RES, both in the monolayer/two-dimensional (2D) and in the spheroid/three-dimensional (3D) assays. Hemocompatibility studies indicated the safety of the nanoformulation, corroborating the ability to spare non-tumor 3T3 cells and human mononuclear cells of peripheral blood (PBMCs) from cytotoxic effects, indicating its selectivity for the cancerous cells. Furthermore, the synergistic antiproliferative effect was found for both the association of free compounds and the co-encapsulated formulation. These findings highlight the antitumor potential of combining these bioactives, and the proposed nanoformulation as a potentially safe and effective strategy to overcome multidrug resistance in cancer therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2024 Tipo del documento: Article País de afiliación: Brasil

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Pharmaceutics Año: 2024 Tipo del documento: Article País de afiliación: Brasil
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