Liquid formulation containing doxorubicin-loaded lipid-core nanocapsules: Cytotoxicity in human breast cancer cell line and in vitro uptake mechanism

Michelli B Antonow; Ana Carolina C Asbahr; Paula Raddatz; Aline Beckenkamp; Andréia Buffon; Sílvia S Guterres; Adriana R Pohlmann

doi:10.1016/j.msec.2017.03.099

Liquid formulation containing doxorubicin-loaded lipid-core nanocapsules: Cytotoxicity in human breast cancer cell line and in vitro uptake mechanism

Mater Sci Eng C Mater Biol Appl. 2017 Jul 1:76:374-382. doi: 10.1016/j.msec.2017.03.099. Epub 2017 Mar 14.

Authors

Michelli B Antonow¹, Ana Carolina C Asbahr¹, Paula Raddatz², Aline Beckenkamp³, Andréia Buffon³, Sílvia S Guterres³, Adriana R Pohlmann⁴

Affiliations

¹ Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil.
² Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre 91501-970, RS, Brazil.
³ Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil.
⁴ Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil; Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre 91501-970, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil. Electronic address: adriana.pohlmann@ufrgs.br.

PMID: 28482541
DOI: 10.1016/j.msec.2017.03.099

Abstract

Cancer is a major public health problem in the world, being breast cancer the most frequent cancer affecting women. Despite advances in detection and treatment, mortality rates remain high. Therefore, new approaches for breast cancer treatments are necessary. In this study, our objective was to develop a liquid formulation containing doxorubicin-loaded lipid-core nanocapsules (DOX-LNC), to evaluate the in vitro antiproliferative activity and to determine the nanocapsules uptake by MCF-7 cells. Lipid-core nanocapsules (LNC), blank formulation, and DOX-LNC, proposed treatment, were prepared by self-assembling using the solvent displacement method. Hydrodynamic mean diameters (z-average) were respectively 191±31nm and 230±23nm presenting narrow size distributions. Drug content was 0.102±0.029mgmL^-1 with an encapsulation efficiency higher than 90%. Formulations were applied to semiconfluent MCF-7 cells. After 24h, LNC showed no cytotoxicity, while DOX-LNC showed an IC₅₀ of 4.49 micromolar. After 72h of incubation, DOX-LNC showed an IC₅₀ of 1.60 micromolar demonstrating a sustained effect. The nanocapsules were internalized by endocytosis mediated by caveolin and by fluid phase endocytosis, which are active transport mechanisms. In conclusion, the liquid formulation containing DOX-LNC showed to be a promising product for the breast cancer treatment opening new avenues for further in vivo studies.

Keywords: Breast cancer; Caveolin; Cytotoxicity; Doxorubicin; Lipid-core nanocapsules; Polymer.

MeSH terms

Breast Neoplasms*
Cell Line, Tumor
Doxorubicin
Humans
Lipids
MCF-7 Cells
Nanocapsules

Substances

Lipids
Nanocapsules
Doxorubicin