title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Samuel V
authors: SV
authors: Mussi
authors: Rupa
authors: R
authors: Sawant
authors: Federico
authors: F
authors: Perche
authors: Mônica C
authors: MC
authors: Oliveira
authors: Ricardo B
authors: RB
authors: Azevedo
authors: Lucas A M
authors: LA
authors: Ferreira
authors: Vladimir P
authors: VP
authors: Torchilin
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002626:Chemistry, Pharmaceutical; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004281:Docosahexaenoic Acids; D004317:Doxorubicin