Chen Cheng, Yu Chung Him, Cheng Yin Chung, Yu Peter H F, Cheung Man Ken
State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, PR China.
Biomaterials. 2006 Sep;27(27):4804-14. doi: 10.1016/j.biomaterials.2006.04.039. Epub 2006 Jun 5.
New amorphous amphiphilic triblock copolymers of poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) (PHB-PEG-PHB) were synthesized using the ring-opening copolymerization of beta-butyrolactone monomer. They were characterized by fluorescence, SEM and (1)H NMR. These triblock copolymers can form biodegradable nanoparticles with core-shell structure in aqueous solution. Comparing to the poly(ethylene oxide)-PHB-poly(ethylene oxide) (PEO-PHB-PEO) copolymers, these nanoparticles exhibited much smaller critical micelle concentrations and better drug loading properties, which indicated that the nanoparticles were very suitable for delivery carriers of hydrophobic drugs. The drug release profile monitored by fluorescence showed that the release of pyrene from the PHB-PEG-PHB nanoparticles exhibited the second-order exponential decay behavior. The initial biodegradation rate of the PHB-PEG-PHB nanoparticles was related to the enzyme amount, the initial concentrations of nanoparticle dispersions and the PHB block length. The biodegraded products detected by (1)H NMR contained 3HB monomer, dimer and minor trimer, which were safe to the body.
通过β-丁内酯单体的开环共聚反应合成了新型的聚(3-羟基丁酸酯)-聚(乙二醇)-聚(3-羟基丁酸酯)(PHB-PEG-PHB)无定形两亲性三嵌段共聚物。通过荧光、扫描电子显微镜和核磁共振氢谱对其进行了表征。这些三嵌段共聚物在水溶液中可形成具有核壳结构的可生物降解纳米颗粒。与聚环氧乙烷-PHB-聚环氧乙烷(PEO-PHB-PEO)共聚物相比,这些纳米颗粒表现出小得多的临界胶束浓度和更好的载药性能,这表明这些纳米颗粒非常适合作为疏水性药物的递送载体。通过荧光监测的药物释放曲线表明,芘从PHB-PEG-PHB纳米颗粒中的释放呈现二级指数衰减行为。PHB-PEG-PHB纳米颗粒的初始生物降解速率与酶量、纳米颗粒分散体的初始浓度以及PHB嵌段长度有关。通过核磁共振氢谱检测到的生物降解产物包含3HB单体、二聚体和少量三聚体,它们对人体是安全的。