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Pharm Res. 2009 Apr;26(4):946-57. doi: 10.1007/s11095-008-9797-7. Epub 2008 Dec 20.

Doxorubicin-loaded polymeric micelles based on amphiphilic polyphosphazenes with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and ethyl glycinate as side groups: synthesis, preparation and in vitro evaluation.

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  • 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yu-Hang-Tang Road, Hangzhou, 310058, China.



To construct novel doxorubicin-loaded polymeric micelles based on polyphosphazenes containing N-isopropylacrylamide copolymers and evaluate their various properties as well as in vitro anticancer effect.


These amphiphilic graft polyphosphazenes PNDGP were synthesized via thermal ring-opening polymerization and subsequent two-step substitution reaction of hydrophilic and hydrophobic side groups. Micellization behavior in an aqueous phase was confirmed by fluorescence technique, DLS and TEM. Doxorubicin (DOX) was physically loaded into micelles by dialysis or O/W emulsion method. CLSM and MTT test were applied to observe intracellular drug distribution and determine cytotoxicity of drug-loaded micelles on Hela and HepG2 cells lines, respectively.


A series of PNDGPs with controlled substitution ratios were obtained. Poly(NIPAm-co-DMAA) can act as hydrophilic segments in micellular system since its LCST was over 37 degrees C when PNIPAm was copolymerized with DMAA. The CMC value was decreased with the increase of Glyet content. In addition, more hydrophobic group content introduced into the polymer would facilitate DOX encapsulation into the micelle. DOX-loaded micelle could achieve comparative cytotoxicity as free drug via endocytosis and succedent drug release into cytoplasm of cancer cells.


The results suggest that these polymers might be used as potential carriers of hydrophobic anti-tumor drug for cancer therapy.

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