Synthesis and characterization of star block copolymer for controlled drug delivery

Abstract

Amphiphilic multiarm block copolymers of hydrophobic poly(methyl methacrylate) core and hydrophilic poly(acrylic acid) corona has been synthesized, characterized and proposed for an anticancer drug that is 5 Florouracil (5FU). 3 arm, 4 arm and 6 arm PMMA-b-PtBA (poly(methyl methacrylate-block-poly(tertiary butyl acrylate)) copolymers with molecular weights from 18 kDa to 80 kDa were synthesized by Atomic Transfer Radical Polymerization and reacted into PMMA-b-PAA (poly(methyl methacrylate-block-poly(acrylic acid)) by hydrolysis of tBA chains. Optimum molecular weight and hydrophobic core ratio was determined by evaluation of critical micelle concentrations and maximum loading capacities with pyrene. Loading method was selected among simple equilibrium, solvent deposition, salting out and dialysis methods. Dialysis method yielded the highest loading contents of model drug indomethacin. Optimum loading conditions in terms of temperature, duration, pH and polymer concentration were determined with anticancer drug 5FU. 4 arm PMMA-b-PAA with molecular weight 18000 Da and hydrophobic core ratio 0.27 was proposed for controlled delivery of 5FU. Optimum loading conditions were determined as 15C in acidic aqueous medium with pH 1.0-1.5 and loading interval as 4 hours. Minimum polymer concentration was estimated to be 2000 mg/L for an optimum loading. Drug loaded particles were characterized by FTIR, TGA, DTG and DSC. 5FU loaded PMMA-b-PAA samples with drug contents about 14-20 % were investigated by a continuous operation where a diffusion cell was employed to monitor release profiles. Controlled release of 5FU with zero order release kinetics for 18 days was provided by 4 arm PMMA-b-PAA. Biodegradation of loaded particles were monitored through particle size analysis by Dynamic Light Scattering and Atomic Force Microscopy.