Optimisation of processing variables effective on self-assembly of folate targeted Synpronic-based micelles for...

Polymeric micelles (PMs) were formulated as nano carriers for docetaxel intended for both intravenous administration and improve therapeutic efficacy of the drug. The PMs were formulated using folic acid conjugated Synpronic F127-cholesterol copolymer and were optimised using a 2(3) full factorial design. The effects of different formulation variables were evaluated on the particle size, entrapment efficiency (EE), zeta potential and release efficiency of the micelles. The in vitro cytotoxicity of DTX-loaded FA targeted micelles was studied on B16F10 melanoma cells which over expressed FA receptor. Among the studied single factors, solvent type was the most effective parameter on the EE and release efficiency. Polymer/drug ratio had the most considerable effect on the particle size while, zeta potential was more affected by temperature. Finally, the PMs with polymer/drug ratio of 12 prepared at 25°C by dimethyl sulfoxide as the dialyzing solvent was shown to be the optimum formulation with desirability factor of 84.9%. The optimised formulation exhibited a particle size of 171.3 nm, 99.59% drug EE, zeta potential of -7.80 mV, drug release efficiency of about 70% at 144 h and polydispersity index of 0.32. The MTT assay indicated DTX-loaded FA targeted micelles were significantly more cytotoxic than non-targeted micelles and free drug.