1. Preparation and characterization of polymeric micelles loaded with a potential anticancer prodrug
- Author
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Marinelli, Lisa, Cacciatore, Ivana, Fornasari, Erika, Gasbarri, Carla, Angelini, Guido, Marrazzo, Agostino, Pandolfi, Assunta, Mandatori, Domitilla, Shi, Yang, Van Nostrum, Cornelus F., Hennink, Wim E., Di Stefano, Antonio, Sub Drug delivery, Dep Farmaceutische wetenschappen, Pharmaceutics, Sub Drug delivery, Dep Farmaceutische wetenschappen, and Pharmaceutics
- Subjects
Materials science ,micelles ,Amphiphilic block copolymers ,Drug delivery system ,Pharmaceutical Science ,02 engineering and technology ,macromolecular substances ,anticancer ,010402 general chemistry ,01 natural sciences ,Micelle ,chemistry.chemical_compound ,Amphiphile ,HPMA ,Taverne ,Copolymer ,Organic chemistry ,Methacrylamide ,chemistry.chemical_classification ,technology, industry, and agriculture ,Polymer ,Prodrug ,021001 nanoscience & nanotechnology ,Combinatorial chemistry ,0104 chemical sciences ,chemistry ,prodrug ,Drug delivery ,Polymeric micelles ,R-(+)-MRJF4 ,0210 nano-technology ,Ethylene glycol - Abstract
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.
- Published
- 2016