Facile fabrication of diblock methoxy poly(ethylene glycol)-poly(tetramethylene carbonate) and its self-assembled micelles as drug carriers.
AB type diblock methoxy poly(ethylene glycol)-b-poly(tetramethylene carbonate) (mPEG-PTeMC) copolymers were designed for the first time and used as carriers for the sustained release of the hydrophobic drug ibuprofen. In this paper, we developed a facile ring-opening polymerization (ROP) method to prepare mPEG-PTeMC copolymers under the catalysis of Novozym-435 lipase. Attractively, the polymerization has been successfully performed at 30 degrees C, close to room temperature. The data show that the copolymer compositions agree well with the feed ratio of TeMC to mPEG, indicating the controllable feature of the polymerization. The copolymer structures were characterized by (1)H NMR, IR, SEC, and DSC measurements. mPEG-PTeMC exhibits no apparent in vitro cytotoxicity toward human embryonic kidney transformed 293T cells. Those amphiphilic copolymers can readily self-assemble into nanosized micelles (about 150 nm) in aqueous solution. Their critical micelle concentrations are in the range of (1.6-9.3) x 10(-7) mol/L, determined by fluorescence spectroscopy. The micelles present high stability in PBS solution, with no obvious change in micelle diameters over 5 days. Ibuprofen can be loaded effectively in mPEG-PTeMC micelles, and its sustained release behavior is observed. Transmission electron microscopy shows that the well-dispersed spherical micelles are around 25 nm in diameter, while the diameter is 30 nm after loading ibuprofen. The release rate increases when the chain length of the PTeMC block decreases. These properties show that the micelles self-assembled from mPEG-PTeMC copolymers would have great potential as carriers for the effective encapsulation as well as sustained release of hydrophobic drugs.
Feng
Jun
J
Key Laboratory of Biomedical Polymers (The Ministry of Education), Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China. fengjun@whu.edu.cn
Su
Wei
W
Wang
Hua-fen
HF
Huang
Fu-wei
FW
Zhang
Xian-zheng
XZ
Zhuo
Ren-xi
RX
D055162:Biocatalysis / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002850:Chromatography, Gel; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D005453:Fluorescence; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D008049:Lipase / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D013696:Temperature; D013997:Time Factors
D004337:Drug Carriers; D008823:Micelles; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D008049:Lipase; D007052:Ibuprofen