Solid lipid nanoparticles co-loaded with doxorubicin and α-tocopherol succinate are effective against drug-resistant cancer cells in monolayer and 3-D spheroid cancer cell models.

Autor: Oliveira MS; Department of Phamaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Aryasomayajula B; Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA., Pattni B; Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA., Mussi SV; Department of Phamaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Ferreira LAM; Department of Phamaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil., Torchilin VP; Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA. Electronic address: v.torchilin@neu.edu.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2016 Oct 15; Vol. 512 (1), pp. 292-300. Date of Electronic Publication: 2016 Aug 26.
DOI: 10.1016/j.ijpharm.2016.08.049
Abstrakt: This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopherol succinate (TS) and to evaluate its potential to overcome drug resistance and to increase antitumoral effect in MCF-7/Adr and NCI/Adr cancer cell lines. The SLN were prepared by a hot homogenization method and characterized for size, zeta potential, entrapment efficiency (EE), and drug loading (DL). The cytotoxicity of SLN or penetration was evaluated in MCF-7/Adr and NCI/adr as a monolayer or spheroid cancer cell model. The SLN showed a size in the range of 74-80nm, negative zeta potential, EE of 99%, and DL of 67mg/g. The SLN co-loaded with Dox and TS showed a stronger cytotoxicity against MCF-7/Adr and NCI/Adr cells. In the monolayer model, the doxorubicin co-localization as a free and encapsulated form was higher for the encapsulated drug in MCF-7/Adr and NCI/adr, suggesting a bypassing of P-glycoprotein bomb efflux. For cancer cell spheroids, the SLN co-loaded with doxorubicin and TS showed a prominent cytotoxicity and a greater penetration of doxorubicin.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE