Stanković Milica, Tomar Jasmine, Hiemstra Christine, Steendam Rob, Frijlink Henderik W, Hinrichs Wouter L J
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands.
Eur J Pharm Biopharm. 2014 Jul;87(2):329-37. doi: 10.1016/j.ejpb.2014.02.012. Epub 2014 Mar 3.
In this study, the in vitro release of proteins from novel, biodegradable phase-separated poly(ε-caprolactone-PEG)-block-poly(ε-caprolactone), [PCL-PEG]-b-[PCL]) multiblock copolymers with different block ratios and with a low melting temperature (49-55°C) was studied. The effect of block ratio and PEG content of the polymers (i.e. 22.5, 37.5 and 52.5 wt%) as well as the effect of protein molecular weight (1.2, 5.8, 14, 29 and 66 kDa being goserelin, insulin, lysozyme, carbonic anhydrase and albumin, respectively) on protein release was investigated. Proteins were spray-dried with inulin as stabilizer to obtain a powder of uniform particle size. Spray-dried inulin-stabilized proteins were incorporated into polymeric implants by hot melt extrusion. All incorporated proteins fully preserved their structural integrity as determined after extraction of these proteins from the polymeric implants. In general, it was found that the release rate of the protein increased with decreasing molecular weight of the protein and with increasing the PEG content of the polymer. Swelling and degradation rate of the copolymer increased with increasing PEG content. Hence, release of proteins of various molecular weights from [PCL-PEG]-b-[PCL] multi-block copolymers can be tailored by varying the PEG content of the polymer.
在本研究中，对新型、可生物降解的相分离聚（ε-己内酯-聚乙二醇）-嵌段-聚（ε-己内酯），即[PCL-PEG]-b-[PCL]多嵌段共聚物在不同嵌段比例且低熔点（49 - 55°C）下蛋白质的体外释放情况进行了研究。考察了聚合物的嵌段比例和聚乙二醇含量（即22.5%、37.5%和52.5%重量比）以及蛋白质分子量（分别为1.2 kDa、5.8 kDa、14 kDa、29 kDa和66 kDa的戈舍瑞林、胰岛素、溶菌酶、碳酸酐酶和白蛋白）对蛋白质释放的影响。蛋白质与菊粉作为稳定剂进行喷雾干燥以获得粒径均匀的粉末。通过热熔挤出将喷雾干燥的菊粉稳定化蛋白质掺入聚合物植入物中。从聚合物植入物中提取这些蛋白质后测定发现，所有掺入的蛋白质都完全保持了其结构完整性。总体而言，发现蛋白质的释放速率随蛋白质分子量的降低以及聚合物聚乙二醇含量的增加而提高。共聚物的溶胀和降解速率随聚乙二醇含量的增加而增加。因此，通过改变聚合物的聚乙二醇含量，可以调整[PCL-PEG]-b-[PCL]多嵌段共聚物中各种分子量蛋白质的释放。
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