Rodrigo Cé1, Vladimir Lavayen2, Gabriela Klein Couto3, João Guilherme Barreto De Marchi4, Barbara Zoche Pacheco5, Letícia Antunes Natividade5, Tiago Ost Fracari2, Taiane Medeiro Ciocheta4, Aline de Cristo Soares Alves4, Denise Soledade Jornada4, Silvia Stanisçuaski Guterres4, Fabiana Seixas3, Tiago Collares3, Adriana Raffin Pohlmann6,7. 1. Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, 90610-000, Brazil. rodrigoce_@hotmail.com. 2. Departamento de Química Inorgânica and Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil, Av. Bento Gonçalves, 9500, Porto Alegre, 91501-970, Brazil. 3. Programa de Pós-Graduação em Biotecnologia, Grupo de Pesquisa em Oncologia Celular e Molecular, Laboratório de Biotecnologia do Cancer Biotecnologia/Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, Brazil. 4. Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, 90610-000, Brazil. 5. Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, 91501-970, Brazil. 6. Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre, 90610-000, Brazil. adriana.pohlmann@ufrgs.br. 7. Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, 91501-970, Brazil. adriana.pohlmann@ufrgs.br.
Abstract
PURPOSE: Folic acid-doxorubicin-double-functionalized-lipid-core nanocapsules (LNC-CS-L-Zn+2-DOX-FA) were prepared, characterized, and evaluated in vitro against ovarian and bladder cancer cell lines (OVCAR-3 and T24). METHODS: LNC-CS-L-Zn+2-DOX-FA was prepared by self-assembly and interfacial reactions, and characterized using liquid chromatography, particle sizing, transmission electron microscopy, and infrared spectroscopy. Cell viability and cellular uptake were studied using MTT assay and confocal microscopy. RESULTS: The presence of lecithin allows the formation of nanocapsules with a lower tendency of agglomeration, narrower size distributions, and smaller diameters due to an increase in hydrogen bonds at the surface. LNC-L-CS-Zn+2-DOX-FA, containing 98.00 ± 2.34 μg mL-1 of DOX and 105.00 ± 2.05 μg mL-1 of FA, had a mean diameter of 123 ± 4 nm and zeta potential of +12.0 ± 1.3 mV. After treatment with LNC-L-CS-Zn+2-DOX-FA (15 μmol L-1 of DOX), T24 cells had inhibition rates above 80% (24 h) and 90% (48 h), whereas OVCAR-3 cells showed inhibition rates of 68% (24 h) and 93% (48 h), showing higher cytotoxicity than DOX.HCl. The fluorescent-labeled formulation showed a higher capacity of internalization in OVCAR-3 compared to T24 cancer cells. CONCLUSION: Lecithin favored the increase of hydrogen bonds at the surface, leading to a lower tendency of agglomeration for nanocapsules. LNC-CS-L-Zn+2-DOX-FA is a promising therapeutic agent against tumor-overexpressing folate receptors.
PURPOSE:Folic acid-doxorubicin-double-functionalized-lipid-core nanocapsules (LNC-CS-L-Zn+2-DOX-FA) were prepared, characterized, and evaluated in vitro against ovarian and bladder cancer cell lines (OVCAR-3 and T24). METHODS:LNC-CS-L-Zn+2-DOX-FA was prepared by self-assembly and interfacial reactions, and characterized using liquid chromatography, particle sizing, transmission electron microscopy, and infrared spectroscopy. Cell viability and cellular uptake were studied using MTT assay and confocal microscopy. RESULTS: The presence of lecithin allows the formation of nanocapsules with a lower tendency of agglomeration, narrower size distributions, and smaller diameters due to an increase in hydrogen bonds at the surface. LNC-L-CS-Zn+2-DOX-FA, containing 98.00 ± 2.34 μg mL-1 of DOX and 105.00 ± 2.05 μg mL-1 of FA, had a mean diameter of 123 ± 4 nm and zeta potential of +12.0 ± 1.3 mV. After treatment with LNC-L-CS-Zn+2-DOX-FA (15 μmol L-1 of DOX), T24 cells had inhibition rates above 80% (24 h) and 90% (48 h), whereas OVCAR-3 cells showed inhibition rates of 68% (24 h) and 93% (48 h), showing higher cytotoxicity than DOX.HCl. The fluorescent-labeled formulation showed a higher capacity of internalization in OVCAR-3 compared to T24 cancer cells. CONCLUSION:Lecithin favored the increase of hydrogen bonds at the surface, leading to a lower tendency of agglomeration for nanocapsules. LNC-CS-L-Zn+2-DOX-FA is a promising therapeutic agent against tumor-overexpressing folate receptors.
Entities:
Keywords:
OVCAR-3: ovarian cancer line; T24: bladder cancer line; doxorubicin; folic acid; lipid-core nanocapsules
Authors: Eduardo A Bender; Marcela F Cavalcante; Márcia D Adorne; Letícia M Colomé; Sílvia S Guterres; Dulcinéia S P Abdalla; Adriana R Pohlmann Journal: Pharm Res Date: 2014-05-08 Impact factor: 4.200
Authors: Giovanni Di Lorenzo; Giuseppe Ricci; Giovanni Maria Severini; Federico Romano; Stefania Biffi Journal: Theranostics Date: 2018-07-30 Impact factor: 11.556