Statistically developed docetaxel-laden mixed micelles for improved therapy of breast cancer

Abstract

Docetaxel (DTX) has poor solubility, serious side effects, and multi-drug resistance (MDR) limiting its use in cancer treatment. Hence, the present study aimed to formulate and develop docetaxel mixed micelles (DTX MMs) for breast cancer treatment. DTX MMs were prepared from a mixture of docetaxel, TPGS, and Poloxamer 188 by using the solvent evaporation method. A 32 factorial design was applied to examine the combined effect of two formulation variables, each at 3 levels, and the 9 possible combinations of DTX MMs. The concentration of TPGS (X1) and concentration of Poloxamer 188 (X2) were independent variables. Whereas, particle size (Y1), and % entrapment efficiency (%EE) (Y2) were dependent variables. DTX MMs were evaluated for particle size analysis, TEM, %EE, in vitro drug release, %hemolysis, and stability study. DTX MMs composition (F6) was optimized based on particle size (143.2 nm), zeta potential (-7.5 mV) and %EE (81%). The TEM images showed spherical-shaped MMs. DTX MMs showed moderately higher IC50 value, indicating lower cytotoxicity when compared to plain DTX against MCF-7 cells. Docetaxel's sustained release from MMs decreased its exposure to normal tissue. Studies using IR, DSC, and P-XRD showed no significant incompatibility. DTX MMs would be a potential therapy for chemotherapy against breast cancer

Keywords

• Docetaxel
• Mixed micelles
• Poloxamer 188
• TPGS
• Breast cancer
• Cytotoxicity study