Preparation and characterization of polymeric micelles loaded with a potential anticancer prodrug

Polymeric micelles based on HPMA [N-(2-hydroxypropyl) methacrylamide] polymers were recently evaluated as drug delivery systems of several anticancer drugs. The development of polymeric micelles to solubilize R-(+)-MRJF4, a potential anticancer prodrug, is reported in this paper. Two different amphiphilic block copolymers based on PEG-HPMA [(ω-methoxypoly(ethylene glycol)-b-(N-(2-benzoyloxy-propyl) methacrylamide)-co-(N-(2-lactoyloxypropyl) methacrylamide) (PEG-HPMA-Bz-L) and (ω-methoxy poly(ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide (PEG-HPMA-Bz)] were synthesized and investigated for this purpose. Results showed that both polymers were able to efficiently solubilize the drug at concentrations of 2 and 4 mg/mL and polymer concentration of 9 mg/mL yielding polymeric micelles with a size of 53-83 nm. Release studies showed that the formulation obtained using PEG-HPMA-Bz-L slowly released R-(+)-MRJF4 for 7-8 days. Moreover, cytotoxicity studies performed on C6 glioma cells revealed that, after 48 h, R-(+)-MRJF4-loaded PEG-HPMA-Bz and PEG-HPMA-Bz-L micelles possessed a higher antiproliferative activity when compared to free R-(+)-MRJF4, implying that the formulations could be internalized by the cells. Taken together, our results suggest that PEG-HPMA-Bz-L polymeric micelles are interesting to optimize the therapeutic efficacy of R-(+)-MRJF4.