Self-assembled micelles from an amphiphilic hyperbranched copolymer with polyphosphate arms for drug delivery.
A novel type of amphiphilic hyperbranched multiarm copolymer [H40-star-(PLA-b-PEP-OH)] was synthesized through a two-step ring-opening polymerization (ROP) procedure and applied to drug delivery. First, Boltorn H40 was used as macroinitiator for the ROP of L-lactide to form the intermediate (H40-star-PLA-OH). Then, the ROP of ethyl ethylene phosphate was further initiated to produce H40-star-(PLA-b-PEP-OH). The resulting hyperbranched multiarm copolymers were characterized by (1)H, (13)C, and (31)P NMR, GPC, and FTIR spectra. Benefiting from the amphiphilic structure, H40-star-(PLA-b-PEP-OH) was able to self-assemble into micelles in water with an average diameter of 130 nm. In vitro evaluation of these micelles demonstrated their excellent biocompatibility and efficient cellular uptake by methyl tetrazolium assay, flow cytometry, and confocal laser scanning microscopy measurements. Doxorubicin-loaded micelles were investigated for the proliferation inhibition of a Hela human cervical carcinoma cell line, and the Doxorubicin dose required for 50% cellular growth inhibition was found to be 1 microg/mL. These results indicate that H40-star-(PLA-b-PEP-OH) micelles can be used as safe, promising drug-delivery systems.
Liu
Jinyao
J
School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
Huang
Wei
W
Pang
Yan
Y
Zhu
Xinyuan
X
Zhou
Yongfeng
Y
Yan
Deyue
D
D000818:Animals; D002470:Cell Survival; D011232:Chemical Precipitation; D004337:Drug Carriers / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008823:Micelles; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D041681:NIH 3T3 Cells; D011108:Polymers / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D011122:Polyphosphates / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011122:Polyphosphates