Kaitian X, Denkbaş E B, Küçükyavuz Z
Hacettepe University, Chemical Engineering Department and Bioengineering Division, Ankara, Turkey.
J Biomater Sci Polym Ed. 1995;7(4):359-73. doi: 10.1163/156856295x00373.
In this study we attempted to develop a novel drug delivery system in the form of polymeric micelles. In order to obtain polymer chains with micelle forming abilities, we have proposed to produce copolymers by transesterification of poly(DL-lactic acid)(PDLLA)(as the hydrophobic segment) and polyethylene glycol (PEG) (as the hydrophilic segment). We first produced homopolymers of PDLLA with low molecular weights by condensation polymerization of DL-lactic acid. The PDLLA homopolymer with an average molecular weight of 1866 +/- 100 was then transesterified with PEG with a molecular weight range of 3300-4000. By changing the ratio of PEG to PDLLA, we were able to produce copolymers with different chain structures, and therefore, with different micelle forming abilities. FTIR, 1H-NMR, DSC, and GPC studies were performed to describe the structures of these PDLLA/PEG copolymers. Micelles of these copolymers were characterized by light scattering. We selected a model drug, i.e. adriamycin, and obtained the drug loadings to the PDLLA/PEG copolymer micelles. The maximum drug loading was about 12 mg g-1. We found that these micelles were degraded in phosphate buffer (pH 7.4 and temperature 37 degrees C) in about 5-6 weeks. We also investigated the release of adriamycin from these PDLLA/PEG micelles, and concluded that the drug release from these micelles was mainly 'degradation controlled'.
在本研究中，我们试图开发一种以聚合物胶束形式存在的新型药物递送系统。为了获得具有形成胶束能力的聚合物链，我们提议通过聚（DL-乳酸）（PDLLA）（作为疏水链段）与聚乙二醇（PEG）（作为亲水链段）的酯交换反应来制备共聚物。我们首先通过DL-乳酸的缩聚反应制备了低分子量的PDLLA均聚物。然后将平均分子量为1866±100的PDLLA均聚物与分子量范围为3300 - 4000的PEG进行酯交换反应。通过改变PEG与PDLLA的比例，我们能够制备出具有不同链结构、因而具有不同胶束形成能力的共聚物。进行了傅里叶变换红外光谱（FTIR）、核磁共振氢谱（1H-NMR）、差示扫描量热法（DSC）和凝胶渗透色谱法（GPC）研究来描述这些PDLLA/PEG共聚物的结构。这些共聚物的胶束通过光散射进行表征。我们选择了一种模型药物，即阿霉素，并测定了其在PDLLA/PEG共聚物胶束中的载药量。最大载药量约为12 mg g-1。我们发现这些胶束在磷酸盐缓冲液（pH 7.4，温度37℃）中大约5 - 6周内降解。我们还研究了阿霉素从这些PDLLA/PEG胶束中的释放情况，并得出结论，这些胶束中的药物释放主要是“降解控制”的。
