Novel micelles from graft polyphosphazenes as potential anti-cancer drug delivery systems: drug encapsulation and in vitro evaluation.
In this study, a new class of amphiphilic methoxy-poly(ethylene glycol) grafted polyphosphazene with glycine ethyl ester side groups (PPP-g-PEG/GlyEt) was synthesized and characterized. An anti-cancer agent doxorubicin (DOX) was encapsulated into polymeric micelles derived from those copolymers, which exhibited considerably strong impact on micelle morphology: turned the rod-like and spherical drug free micelles into spheres and vesicles respectively. The in vitro release behavior of those drug-loaded micelles exhibits a sustained release manner and is affected by drug content. Cytotoxicity assay against adriamycin-resistant human breast cancer MCF-7 cell line showed that drug-loaded micelles based on PPP-g-PEG/GlyEt micelles can effectively suppress cell proliferation and the cytotoxicity was both time and concentration related, an enhanced cytotoxicity was observed either with increasing drug concentration or with prolonged incubation time. Moreover, flow cytometry results revealed a particle size dependency in cellular uptake of drug-loaded micelles. These findings suggest that the present copolymers can encapsulate water insoluble anti-cancer agents and contribute to improve drug sensitivity of adriamycin-resistant cell line.
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Cheng
C
Zheng
Liyan
L
Qiu
Xiaping
X
Yao
Kangjie
K
Zhu
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D005434:Flow Cytometry; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010316:Particle Size; D010753:Phosphoranes / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
D000970:Antineoplastic Agents; D008823:Micelles; D009943:Organophosphorus Compounds; D010753:Phosphoranes; D011108:Polymers; C108974:poly(phosphazene); D011092:Polyethylene Glycols; C022010:glycine ethyl ester; D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol; C022601:hexachlorocyclotriphosphazene; D005998:Glycine