Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
InnoCore Pharmaceuticals, L.J. Zielstraweg 1, 9713 GX, Groningen, The Netherlands.
Int J Pharm. 2015 Mar 1;480(1-2):73-83. doi: 10.1016/j.ijpharm.2015.01.007. Epub 2015 Jan 6.
In this study, water-swellable multiblock copolymers composed of semi-crystalline poly(ϵ-caprolactone) [PCL] blocks and amorphous blocks consisting of poly(D,L-lactide) (PDLLA) and poly(ethylene glycol) (PEG) [PDLLA-PEG] were synthesized. The block ratio of these [PDLLA-PEG]-b-[PCL] multiblock copolymers was varied and the degradation of implants prepared of these polymers by hot melt extrusion (HME) was compared with implants prepared of [PCL-PEG]-b-[PCL], a copolymer which has been described previously (Stanković et al., 2014). It was shown that the initial degradation rate of the [PDLLA-PEG]-b-[PCL] multiblock copolymers increased with increasing the content of amorphous [PDLLA-PEG] block and that the degradation rate of these multiblock copolymers was faster than that of the [PCL-PEG]-b-[PCL] multiblock copolymers due to rapid degradation of the [PDLLA-PEG] block. Furthermore, the release of the model proteins lysozyme and bovine serum albumin from polymer implants prepared by HME was studied. It was found that the protein release from [PDLLA-PEG]-b-[PCL] copolymers was incomplete, which is not acceptable for any application of these polymers. Besides, [PCL-PEG]-b-[PCL] copolymers showed slow and continuous release. We hypothesize that the incomplete release is explained by an irreversible interaction between the proteins and polymer degradation products or by entrapment of the protein in the hydrophobic and non-swellable polymer matrix that was left after degradation and loss of the hydrophilic [PDLLA-PEG] blocks from the degrading polymer.
在这项研究中，合成了由半结晶聚（ε-己内酯）[PCL]嵌段和由聚（D，L-丙交酯）（PDLLA）和聚乙二醇（PEG）[PDLLA-PEG]组成的无定形嵌段的可溶胀多嵌段共聚物。这些[PDLLA-PEG]-b-[PCL]多嵌段共聚物的嵌段比发生了变化，并比较了由这些聚合物通过热熔挤出（HME）制备的植入物的降解与先前描述的[PCL-PEG]-b-[PCL]聚合物的降解情况（Stanković 等人，2014）。结果表明，随着无定形[PDLLA-PEG]嵌段含量的增加，[PDLLA-PEG]-b-[PCL]多嵌段共聚物的初始降解速率增加，并且由于[PDLLA-PEG]嵌段的快速降解，这些多嵌段共聚物的降解速率快于[PCL-PEG]-b-[PCL]多嵌段共聚物。此外，还研究了通过 HME 制备的聚合物植入物中模型蛋白溶菌酶和牛血清白蛋白的释放情况。结果发现，从[PDLLA-PEG]-b-[PCL]共聚物中释放的蛋白质不完全，这对于这些聚合物的任何应用都不可接受。此外，[PCL-PEG]-b-[PCL]共聚物表现出缓慢而连续的释放。我们假设，不完全释放是由于蛋白质与聚合物降解产物之间的不可逆相互作用或由于蛋白质被包裹在疏水且不可溶胀的聚合物基质中，该聚合物基质在亲水性[PDLLA-PEG]嵌段降解和丧失后留下。
