Folic Acid-Doxorubicin-Double-Functionalized-Lipid-Core Nanocapsules: Synthesis, Chemical Structure Elucidation, and Cytotoxicity Evaluation on Ovarian (OVCAR-3) and Bladder (T24) Cancer Cell Lines

Author(s):Show less -

Ce, Rodrigo ^[1] ; Lavayen, Vladimir ^{[2, 3]} ; Couto, Gabriela Klein ^[4] ; De Marchi, Joao Guilherme Barreto ^[1] ; Pacheco, Barbara Zoche ^[5] ; Natividade, Leticia Antunes ^[5] ; Fracari, Tiago Ost ^{[2, 3]} ; Ciocheta, Taiane Medeiro ^[1] ; de Cristo Soares Alves, Aline ^[1] ; Jornada, Denise Soledade ^[1] ; Guterres, Silvia Staniscuaski ^[1] ; Seixas, Fabiana ^[4] ; Collares, Tiago ^[4] ; Pohlmann, Adriana Raffin ^{[5, 1]}

Affiliation

^[1] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Farmaceut, Fac Farm, Av Ipiranga 2752, BR-90610000 Porto Alegre, RS - Brazil

^[2] Univ Fed Rio Grande Sul UFRGS, Inst Quim, Dept Quim Inorgan, Av Bento Goncalves 9500, BR-91501970 Porto Alegre, RS - Brazil

^[3] Univ Fed Rio Grande Sul UFRGS, Inst Quim, Programa Posgrad Quim, Av Bento Goncalves 9500, BR-91501970 Porto Alegre, RS - Brazil

^[4] Univ Fed Pelotas, Ctr Desenvolvimento Tecnol, Lab Biotecnol Canc Biotecnol, Programa Posgrad Biotecnol, Grp Pesquisa Oncol Cel, Pelotas, RS - Brazil

^[5] Univ Fed Rio Grande do Sul, Inst Quim, Dept Quim Organ, Av Bento Goncalves 9500, BR-91501970 Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: PHARMACEUTICAL RESEARCH; v. 38, n. 2, p. 301-317, FEB 2021.
• Web of Science Citations: 0

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 mu g mL(-1) of DOX and 105.00 +/- 2.05 mu g 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 mu mol 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. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants