Ryu Won Hyoung, Vyakarnam Murty, Greco Ralph S, Prinz Fritz B, Fasching Rainer J
Rapid Prototyping Laboratory, Mechanical Engineering Department, Stanford University, Rm. 226, Bldg. 530, 440 Escondido Mall, Stanford, CA 94305, USA.
Biomed Microdevices. 2007 Dec;9(6):845-53. doi: 10.1007/s10544-007-9097-8.
A programmable and biodegradable drug delivery device is desirable when a drug needs to be administered locally. While most local drug delivery devices made of biodegradable polymers relied on the degradation of the polymers, the degradation-based release control is often limited by the property of the polymers. Thus, we propose micro-geometry as an alternative measure of controlling drug release. The proposed devices consist of three functional layers: diffusion control layer via micro-orifices, diffusion layer, and drug reservoir layers. A micro-fabrication technology was used to shape an array of micro-orifices and micro-cavities in 85/15PLGA layers. A thin layer of fast degrading 50/50PLGA was placed as the diffusion layer between the 85/15PLGA layers to prevent any burst-type release. To modulate the release of the devices, the dimension and location of the micro-orifices were varied and the responding in vitro release response of tetracycline was monitored over 2 weeks. The release response to the different micro-geometry was prominent and further analyzed by FEM simulation. Comparison of the experiments to the simulated results identified that the variation of micro-geometry influenced also the volume-dependent degradation rate and induced the osmotic pressure.
当需要局部给药时，一种可编程且可生物降解的药物递送装置是很理想的。虽然大多数由可生物降解聚合物制成的局部药物递送装置依赖于聚合物的降解，但基于降解的释放控制通常受到聚合物性质的限制。因此，我们提出将微观几何结构作为控制药物释放的一种替代方法。所提出的装置由三个功能层组成：通过微孔的扩散控制层、扩散层和药物储库层。采用微加工技术在85/15聚乳酸-羟基乙酸共聚物（PLGA）层中形成微孔和微腔阵列。在85/15PLGA层之间放置一层快速降解的50/50PLGA作为扩散层，以防止任何突发式释放。为了调节装置的释放，改变微孔的尺寸和位置，并在两周内监测四环素的体外释放响应。对不同微观几何结构的释放响应很显著，并通过有限元模拟进一步分析。将实验结果与模拟结果进行比较发现，微观几何结构的变化也影响了体积依赖性降解速率并诱导了渗透压。
