title: 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.
abstract: 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.
authors: Department of Phamaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Mariana S
authors: MS
authors: Oliveira
authors: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA.
authors: Bhawani
authors: B
authors: Aryasomayajula
authors: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA.
authors: Bhushan
authors: B
authors: Pattni
authors: Department of Phamaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Samuel V
authors: SV
authors: Mussi
authors: Department of Phamaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors: Lucas A M
authors: LAM
authors: Ferreira
authors: Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA. Electronic address: v.torchilin@neu.edu.
authors: Vladmir P
authors: VP
authors: Torchilin
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000473:pathology; D014810:Vitamin E / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D014810:Vitamin E; D004317:Doxorubicin; C014225:tocophersolan
keywords: Cancer; Doxorubicin; Solid lipid nanoparticles (SLN); Spheroids; α-Tocopherol polyethylene glycol-1000 succinate (TPGS); α-Tocopherol succinate (TS)