期刊
PHARMACEUTICAL RESEARCH
卷 29, 期 6, 页码 1582-1594出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-012-0669-9
关键词
cationic polycarbonate; diblock terpolymer; mPEG-b-poly(ADMC-co-CL); pH-tunable drug release; polymeric micelles
资金
- National Key Basic Research Program of China [2011CB606202, 2009CB930301]
- National Natural Science Foundation of China [20874075]
To design functional drug carriers for fast pH-responsive drug release. Functional diblock terpolymers of monomethoxy poly(ethylene glycol)-block- copoly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione--epsilon-caprolactone) [PEG--poly(ADMC--CL)] were fabricated via biosynthetic pathway. The self-assembled nanosphere and drug-loaded micelles of the copolymers were further prepared by dialysis method. The pH-tunable morphology variation and drug release pattern were observed at different pH. A collection of three PEGylated terpolymers with varied compositions in poly(ADMC--CL) block was designed with high cell-biocompatibility. The copolymers could readily self-assemble into nanoscale micelles (similar to 100 nm) in aqueous medium and exhibit high stability over 80-h incubation in different mediums including deionized water, neutral NaCl solution, and heparin sodium solution. Due to the protonation-deprotonation of tertiary amine groups in ADMC units, acid-induced structural deformation of micelles was disclosed in terms of the variation in CAC value and hydrodynamic size at different pH. Drug loading efficiency was comparable to that of reported PEG-polyester micelles with specifically designed structures purposed for drug-loading improvement. Remarkably accelerated drug release triggered by acidity was distinctly detected for ibuprofen-loaded PEG--poly(ADMC--CL) micelle system, suggesting a fast pH-responsive characteristic. Functional PEG-stabilized micellar carriers with positively charged polyester core were successfully developed for fast pH-responsive drug release.
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