Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil®

MAXIMILIANO CAGEL; EZEQUIEL BERNABEU; LORENA GONZALEZ; EDUARDO LAGOMARSINO; MARCELA ZUBILLAGA; MARCELA A. MORETTON; DIEGO A. CHIAPPETTA; MAXIMILIANO CAGEL; EZEQUIEL BERNABEU; LORENA GONZALEZ; EDUARDO LAGOMARSINO; MARCELA ZUBILLAGA; MARCELA A. MORETTON; DIEGO A. CHIAPPETTA

BIOMEDICINE & PHARMACOTHERAPY = BIOMEDECINE & PHARMACOTHERAPIE.

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Lugar: Paris; Año: 2017 vol. 95 p. 894 - 903

0753-3322

Doxorubicin (DOX) is used as a ?first-line? antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus⁠®, Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery.Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles. The combination of T1107:TPGS (1:3, weight ratio) demonstrated the best physicochemical properties together with a high DL capacity (6.43% w/v). Particularly, DOX in vitro release was higher at acidic tumour microenvironment pH value (5.5) than at physiological counterpart (7.4). The hydrodynamic diameter of the DOX/NaDC-loaded mixed micellar system was 10.7 nm (PDI = 0.239).The in vitro cytotoxicity of the mixed micellar formulation resulted significantly (p < 0.05) higher than Doxil⁠® against ovarian (SKOV-3) and triple-negative breast cancer cells (MDA-MB- 231). Further, the in vitro cellular uptake assays demonstrated a significant increment (p < 0.05) of the DOX intracellular content for the mixed micelles versus Doxil⁠® for both, SKOV-3 (at 2, 4 and 6 h of incubation) and MDA-MB-231 (at 4 h of incubation) cells. These findings suggest that T1107:TPGS (1:3) mixed micelles could be employed as a potential nanotechnological platform for drug delivery of DOX.