MilliporeSigma
  • Home
  • Search Results
  • Novel nanostructured lipid carrier co-loaded with doxorubicin and docosahexaenoic acid demonstrates enhanced in vitro activity and overcomes drug resistance in MCF-7/Adr cells.

Novel nanostructured lipid carrier co-loaded with doxorubicin and docosahexaenoic acid demonstrates enhanced in vitro activity and overcomes drug resistance in MCF-7/Adr cells.

Pharmaceutical research (2014-02-14)
Samuel V Mussi, Rupa Sawant, Federico Perche, Mônica C Oliveira, Ricardo B Azevedo, Lucas A M Ferreira, Vladimir P Torchilin
ABSTRACT

To develop a nanostructured lipid carrier (NLC) co-loaded with doxorubicin and docosahexaenoic acid (DHA) and to evaluate its potential to overcome drug resistance and to increase antitumoral effect in MCF-7/Adr cancer cell line. The NLC was prepared by a hot homogenization method and characterized for size, zeta potential, entrapment efficiency (EE) and drug loading (DL). Drug release was evaluated by dialysis in complete DMEM, and NLC aggregation was assayed in the presence of serum. The cytotoxicity of formulations, doxorubicin uptake or penetration were evaluated in MCF-7 and MCF-7/Adr as monolayer or spheroid models. The formulation had a size of about 80 nm, negative zeta potential, EE of 99%, DL of 31 mg/g, a controlled drug release in DMEM and no particles aggregation in presence of serum. The NLC loaded with doxorubicin and DHA showed the same activity as free drugs against MCF-7 but a stronger activity against MCF-7/Adr cells. In monolayer model, the doxorubicin uptake as free and encapsulated form was similar in MCF-7 but higher for the encapsulated drug in MCF-7/Adr, suggesting a bypassing of P-glycoprotein bomb efflux. For spheroids, the NLC loaded with doxorubicin and DHA showed a prominent cytotoxicity and a greater penetration of doxorubicin. These findings suggest that the co-encapsulation of doxorubicin and DHA in NLC enhances the cytotoxicity and overcomes the doxorubicin resistance in MCF-7/Adr.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, BioUltra, for molecular biology, pH 8.0, ~0.5 M in H2O
Sigma-Aldrich
Oleic acid, natural, FCC
Sigma-Aldrich
Triethanolamine, reagent grade, 98%
Sigma-Aldrich
Oleic acid, technical grade, 90%
Sigma-Aldrich
Oleic acid, meets analytical specification of Ph, Eur., 65.0-88.0% (GC)
Supelco
Oleic acid, analytical standard
Sigma-Aldrich
Triethanolamine, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Triethanolamine, puriss. p.a., ≥99% (GC)
Sigma-Aldrich
Triethanolamine, ≥99.0% (GC)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Oleic acid, suitable for cell culture, BioReagent
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Oleic acid, ≥99% (GC)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ≥98.0% (KT)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, ≥99.0% (KT)
Sigma-Aldrich
Ethylenediaminetetraacetic acid, 99.995% trace metals basis
SAFC
Triethanolamine
Oleic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Triethanolamine, analytical standard
Supelco
Oleic acid, Selectophore, ≥99.0%
Trolamine, European Pharmacopoeia (EP) Reference Standard