title: Experimental design of a liposomal lipid system: A potential strategy for paclitaxel-based breast cancer treatment.
abstract: Paclitaxel (PTX) is widely used as a first-line treatment for patients with metastatic breast cancer; however, its poor water solubility represents a major challenge for parenteral administration. The encapsulation of the PTX in drug-delivery systems with high affinity for tumor sites could improve the uptake and increase its therapeutic efficacy. In this work, long-circulating and pH-sensitive PEG-coated (SpHL-PTX) and PEG-folate-coated liposomes containing PTX (SpHL-FT-PTX) were prepared, and the physicochemical properties and in vitro cytotoxic activity were evaluated. Both formulations presented adequate physicochemical properties, including a mean diameter smaller than 200 nm, zeta potential values near the neutral range, and an encapsulation percentage higher than 93%. Moreover, SpHL-FT-PTX showed a good stability after storage for 100 days at 4 °C. The viability studies on breast cancer cell lines (MDA-MB-231 and MCF-7) demonstrated cytotoxic activity more pronounced for SpHL-FT-PTX than for SpHL-PTX or free drug for both tumor cell lines. This activity was reduced to a rate comparable to SpHL-PTX when the cells were previously treated with folic acid in order to saturate the receptors. In contrast, in the normal cell line (L929), cell viability was decreased only by free or liposomal PTX in the highest concentrations. A significantly higher selectivity index was obtained after SpHL-FT-PTX treatment compared to SpHL-PTX and free PTX. Therefore, the results of the present work suggest that SpHL-FT-PTX can be a promising formulation for the treatment of metastatic breast cancer.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Farmácia, Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Rodovia MGT 367-Km 583, 5000, 39100-000, Diamantina, Minas Gerais, Brazil.
authors.forename: Marcos V
authors.initials: MV
authors.lastname: Barbosa
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Liziane O F
authors.initials: LO
authors.lastname: Monteiro
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Farmácia, Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Rodovia MGT 367-Km 583, 5000, 39100-000, Diamantina, Minas Gerais, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Carneiro
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Farmácia, Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Rodovia MGT 367-Km 583, 5000, 39100-000, Diamantina, Minas Gerais, Brazil.
authors.forename: Andréa R
authors.initials: AR
authors.lastname: Malagutti
authors.affiliation: Centro de Tecnologia SENAI-CETEC, Avenida José Cândido da Silveira, 2000, Belo Horizonte, MG 31170-000, Brazil.
authors.forename: José M C
authors.initials: JM
authors.lastname: Vilela
authors.affiliation: Centro de Tecnologia SENAI-CETEC, Avenida José Cândido da Silveira, 2000, Belo Horizonte, MG 31170-000, Brazil.
authors.forename: Margareth S
authors.initials: MS
authors.lastname: Andrade
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mônica C
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Farmácia, Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Rodovia MGT 367-Km 583, 5000, 39100-000, Diamantina, Minas Gerais, Brazil.
authors.forename: Alvaro D
authors.initials: AD
authors.lastname: Carvalho-Junior
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Farmácia, Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Rodovia MGT 367-Km 583, 5000, 39100-000, Diamantina, Minas Gerais, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: elaineleite@ufmg.br.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Leite
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage*; D008081:Liposomes; D017239:Paclitaxel / Q000627:therapeutic use*
chemical_list: D008055:Lipids; D008081:Liposomes; D017239:Paclitaxel
keywords: Folate; Liposomes; Paclitaxel; Targeted drug delivery; pH-sensitivity