Balmayor Elizabeth Rosado, Tuzlakoglu Kadriye, Marques Alexandra P, Azevedo Helena S, Reis Rui L
3B's Research Group - Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
J Mater Sci Mater Med. 2008 Apr;19(4):1617-23. doi: 10.1007/s10856-008-3378-5. Epub 2008 Jan 24.
In many biomedical applications, the performance of biomaterials depends largely on their degradation behavior. For instance, in drug delivery applications, the polymeric carrier should degrade under physiological conditions slowly releasing the encapsulated drug. The aim of this work was, therefore, to develop an enzymatic-mediated degradation carrier system for the delivery of differentiation agents to be used in bone tissue engineering applications. For that, a polymeric blend of starch with polycaprolactone (SPCL) was used to produce a microparticle carrier for the controlled release of dexamethasone (DEX). In order to investigate the effect of enzymes on the degradation behavior of the developed system and release profile of the encapsulated osteogenic agent (DEX), the microparticles were incubated in phosphate buffer solution in the presence of alpha-amylase and/or lipase enzymes (at physiological concentrations), at 37 degrees C for different periods of time. The degradation was followed by gravimetric measurements, scanning electron microscopy (SEM) and Fourier transformed infrared (FTIR) spectroscopy and the release of DEX was monitored by high performance liquid chromatography (HPLC). The developed microparticles were shown to be susceptible to enzymatic degradation, as observed by an increase in weight loss and porosity with degradation time when compared with control samples (incubation in buffer only). For longer degradation times, the diameter of the microparticles decreased significantly and a highly porous matrix was obtained. The in vitro release studies showed a sustained release pattern with 48% of the encapsulated drug being released for a period of 30 days. As the degradation proceeds, it is expected that the remaining encapsulated drug will be completely released as a consequence of an increasingly permeable matrix and faster diffusion of the drug. Cytocompatibility results indicated the possibility of the developed microparticles to be used as biomaterial due to their reduced cytotoxic effects.
在许多生物医学应用中，生物材料的性能很大程度上取决于其降解行为。例如，在药物递送应用中，聚合物载体应在生理条件下降解，缓慢释放封装的药物。因此，这项工作的目的是开发一种酶介导的降解载体系统，用于在骨组织工程应用中递送分化剂。为此，使用淀粉与聚己内酯（SPCL）的聚合物共混物来制备用于地塞米松（DEX）控释的微粒载体。为了研究酶对所开发系统的降解行为和封装的成骨剂（DEX）释放曲线的影响，将微粒在α-淀粉酶和/或脂肪酶（生理浓度）存在下于37℃在磷酸盐缓冲溶液中孵育不同时间。通过重量测量、扫描电子显微镜（SEM）和傅里叶变换红外（FTIR）光谱跟踪降解，并通过高效液相色谱（HPLC）监测DEX的释放。与对照样品（仅在缓冲液中孵育）相比，随着降解时间的增加，观察到重量损失和孔隙率增加，表明所开发的微粒易受酶降解。对于更长的降解时间，微粒直径显著减小，并获得了高度多孔的基质。体外释放研究显示出持续释放模式，在30天内48%的封装药物被释放。随着降解的进行，预计由于基质渗透性增加和药物扩散加快，剩余的封装药物将完全释放。细胞相容性结果表明，所开发的微粒由于其降低的细胞毒性作用而有可能用作生物材料。
