Doxazosin nanoencapsulation improves its in vitro antiproliferative and anticlonogenic effects on breast cancer cells.

Autor: Krai J; Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Beckenkamp A; Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Gaelzer MM; Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Pohlmann AR; Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Guterres SS; Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Filippi-Chiela EC; Faculdade de Medicina, Programa de Pós-Graduação em Hepatologia e Gastroenterologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Salbego C; Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Buffon A; Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil., Beck RCR; Faculdade de Farmácia, Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Electronic address: ruy.beck@ufrgs.br.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2017 Oct; Vol. 94, pp. 10-20. Date of Electronic Publication: 2017 Jul 24.
DOI: 10.1016/j.biopha.2017.07.048
Abstrakt: Doxazosin has been evaluated for the treatment of several types of cancer. Here, the antitumor effect of the nanoencapsulated form of doxazosin was evaluated in an in vitro model of breast cancer (MCF7 cell line). Doxazosin-loaded polymeric nanocapsules (DXZ-NC) were produced by interfacial deposition of preformed polymer with homogeneous aspect, spherical shape, mean diameter of about 130nm, positive zeta potential (+5mV), and encapsulation efficiency close to 35%. The Alamar Blue ® assay and cell counting were carried out to assess cell viability and cell number, respectively. Mechanism of death was evaluated by Annexin/Propidium Iodide staining, while the long-term response was assessed using the clonogenic assay. Nuclear morphometric analysis was investigated using the NMA technique. A significant decrease in cell viability and clonogenicity was observed after the treatment with DXZ-NC when compared to the non-encapsulated drug. All treatments induced apoptosis as the main mechanism of toxicity. In conclusion, the nanoencapsulation of doxazosin improved its in vitro effects in MCF7 cells, without changing the mechanism of cell death underlying its toxicity. This approach was fundamental to reduce the long-term in vitro ability of the remaining tumor cells to form new colonies after the treatment, potentially reducing the risk of tumor recurrence.
(Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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