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A novel enzymatically-mediated drug delivery carrier for bone tissue engineering applications: combining biodegradable starch-based microparticles and differentiation agents

机译：用于骨组织工程应用的新型酶促药物递送载体：结合可生物降解的淀粉基微粒和分化剂

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In many biomedical applications, the performanceof biomaterials depends largely on their degradationbehavior. For instance, in drug delivery applications, thepolymeric carrier should degrade under physiologicalconditions slowly releasing the encapsulated drug. The aimof this work was, therefore, to develop an enzymaticmediateddegradation carrier system for the delivery ofdifferentiation agents to be used in bone tissue engineeringapplications. For that, a polymeric blend of starch withpolycaprolactone (SPCL) was used to produce a microparticlecarrier for the controlled release of dexamethasone(DEX). In order to investigate the effect of enzymes on thedegradation behavior of the developed system and releaseprofile of the encapsulated osteogenic agent (DEX), themicroparticles were incubated in phosphate buffer solutionin the presence of a-amylase and/or lipase enzymes (atphysiological concentrations), at 37 C for different periodsof time. The degradation was followed by gravimetricmeasurements, scanning electron microscopy (SEM) andFourier transformed infrared (FTIR) spectroscopy and therelease of DEX was monitored by high performance liquidchromatography (HPLC). The developed microparticleswere shown to be susceptible to enzymatic degradation, as observed by an increase in weight loss and porosity withdegradation time when compared with control samples(incubation in buffer only). For longer degradation times,the diameter of the microparticles decreased significantlyand a highly porous matrix was obtained. The in vitrorelease studies showed a sustained release pattern with48% of the encapsulated drug being released for a period of30 days. As the degradation proceeds, it is expected thatthe remaining encapsulated drug will be completelyreleased as a consequence of an increasingly permeablematrix and faster diffusion of the drug. Cytocompatibilityresults indicated the possibility of the developed microparticlesto be used as biomaterial due to their reducedcytotoxic effects.
机译：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，从而缓慢释放被包封的药物。因此，这项工作的目的是开发一种酶介导的降解载体系统，用于输送分化剂，以用于骨组织工程应用。为此，使用淀粉与聚己内酯（SPCL）的聚合物共混物来生产用于控制释放地塞米松（DEX）的微粒载体。为了研究酶对发达系统的降解行为和包囊成骨剂（DEX）释放特性的影响，将微粒在磷酸缓冲液中在α-淀粉酶和/或脂肪酶（生理浓度）存在下孵育。 37°C的不同时间段。降解后进行重量分析，扫描电子显微镜（SEM）和傅立叶变换红外（FTIR）光谱，并通过高效液相色谱（HPLC）监测DEX的释放。与对照样品相比（仅在缓冲液中孵育），重量减轻和孔隙率随降解时间的增加而观察到，所开发的微粒表现出对酶降解的敏感性。对于更长的降解时间，微粒的直径显着减小，并且获得了高度多孔的基质。体外释放研究显示了持续释放方式，其中48％的封装药物被释放30天。随着降解的进行，由于药物的可渗透性增加和药物扩散较快，预计剩余的封装药物将被完全释放。细胞相容性结果表明，由于其降低的细胞毒性作用，开发的微粒有可能被用作生物材料。

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