Delivery of methotrexate executed by engineered polymeric micelles intended to improve chemotherapy

Abstract

Development of novel polymeric micelles incorporating methotrexate (MTX) was the objective of present investigation. Solvent evaporation and sonication methods were employed for formulation of micelles, which were optimized on the basis of size, size-distribution (PDI), entrapment efficiency (EE), and drug loading (DL) where sonication time and amount of excipients were selected as optimization parameters. Critical micelles concentration (CMC) of Pluronic (PF-127)-sodium dodecyl sulfate (SDS) mixture was lower than PF127 indicating higher stability of micelles. Loading of MTX in micelles was ensured by 1H NMR characterization. PF-127, PF-127/SDS and PF-127/PC micelles exhibited 80.89±6, 77.67±5 and 78.54±4% in vitro drug release at the end of 24 h. In vitro cytotoxicity of PF127/SDS in MCF-7 cells revealed higher cytotoxic potential (IC50: 0.511±0.437 μM; 6.04 fold than free MTX) which was further supported by higher (84.25%) cell uptake of the micelles. Engineered polymeric micelles ensured safety at 10 mg/kg dose as no major abnormalities in liver and kidney tissues were observed in treated Swiss mice. Stability studies exhibited no significant changes (P<0.05) in the physicochemical and in vitro characterization parameters.