Ginty Patrick J, Barry John J A, White Lisa J, Howdle Steve M, Shakesheff Kevin M
School of Pharmacy, University of Nottingham, Nottingham, UK.
Eur J Pharm Biopharm. 2008 Jan;68(1):82-9. doi: 10.1016/j.ejpb.2007.05.023. Epub 2007 Jul 18.
We report the development of three protein loaded polymer blend and composite materials that modify the release kinetics of the protein from poly(dl-lactic acid) (P(dl)LA) scaffolds. P(dl)LA has been combined with either poly(ethylene glycol) (PEG), poly(caprolactone) (PCL) microparticles or calcium alginate fibres using supercritical CO(2) (scCO(2)) processing to form single and dual protein release scaffolds. P(dl)LA was blended with the hydrophilic polymer PEG using scCO(2) to increase the water uptake of the resultant scaffold and modify the release kinetics of an encapsulated protein. This was demonstrated by the more rapid release of the protein when compared to the release rate from P(dl)LA only scaffolds. For the P(dl)LA/alginate scaffolds, the protein loaded alginate fibres were processed into porous protein loaded P(dl)LA scaffolds using scCO(2) to produce dual release kinetics from the scaffolds. Protein release from the hydrophilic alginate fibres was more rapid in the initial stages, complementing the slower release from the slower degrading P(dl)LA scaffolds. In contrast, when protein loaded PCL particles were loaded into P(dl)LA scaffolds, the rate of protein release was retarded from the slow degrading PCL phase.
我们报道了三种负载蛋白质的聚合物共混物和复合材料的研发情况,这些材料可改变蛋白质从聚(dl-乳酸)(P(dl)LA)支架中的释放动力学。P(dl)LA已与聚乙二醇(PEG)、聚己内酯(PCL)微粒或海藻酸钙纤维结合,采用超临界CO₂(scCO₂)处理形成单一和双重蛋白质释放支架。利用scCO₂将P(dl)LA与亲水性聚合物PEG共混,以增加所得支架的吸水性,并改变包封蛋白质的释放动力学。与仅由P(dl)LA制成的支架的释放速率相比,蛋白质释放更快,这证明了这一点。对于P(dl)LA/海藻酸盐支架,将负载蛋白质的海藻酸纤维通过scCO₂加工成多孔的负载蛋白质的P(dl)LA支架,以产生支架的双重释放动力学。亲水性海藻酸纤维的蛋白质释放在初始阶段更快,补充了降解较慢的P(dl)LA支架的较慢释放。相反,当将负载蛋白质的PCL颗粒加载到P(dl)LA支架中时,蛋白质释放速率从降解缓慢的PCL相延迟。