Watkins Andrew W, Southard Stephanie L, Anseth Kristi S
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USA.
Acta Biomater. 2007 Jul;3(4):439-48. doi: 10.1016/j.actbio.2006.11.006. Epub 2007 Jan 22.
Multilaminated controlled release devices were formed through photopolymerization techniques to produce hydrogels with spatially varying solute loadings and network structures composed of poly(hydroxyl ethyl methacrylate) (PHEMA) and poly(ethylene glycol) (PEG). Using low molecular weight fluorescent dyes as model drugs, the distribution profiles were characterized non-invasively in pseudo-real-time with confocal laser scanning microscopy (CLSM) during release studies. For comparison, theoretical modeling based on Fickian diffusion theory was performed in conjunction with experimental work to identify any deviations from expected behavior and to guide in the development of future devices. In multilaminates composed of only PHEMA, the evolution of dye distribution during release and cumulative release profiles agreed well with theoretically predicted data, indicating continuity of diffusion and insignificant interfacial hindrance between layers. However, in devices composed of alternating layers of PHEMA and PEG, differences from predicted behavior were experimentally observed in both concentration profiles and release rates, suggesting interfacial obstruction of diffusion, possibly due to the formation of interpenetrating networks. Finally, the simultaneous release of two dyes at different rates from a PEG/PHEMA multilaminate was monitored to demonstrate the usefulness of CLSM in understanding the complex temporal changes in solute distributions in gel devices.
通过光聚合技术制备了多层控释装置，以生产具有空间变化溶质负载和由聚甲基丙烯酸羟乙酯（PHEMA）和聚乙二醇（PEG）组成的网络结构的水凝胶。使用低分子量荧光染料作为模型药物，在释放研究期间，利用共聚焦激光扫描显微镜（CLSM）以伪实时方式对分布情况进行非侵入性表征。为了进行比较，结合实验工作进行了基于菲克扩散理论的理论建模，以识别与预期行为的任何偏差，并指导未来装置的开发。在仅由PHEMA组成的多层层合物中，释放过程中染料分布的演变和累积释放曲线与理论预测数据吻合良好，表明扩散的连续性以及层间的界面阻碍不显著。然而，在由PHEMA和PEG交替层组成的装置中，在浓度分布和释放速率方面均通过实验观察到与预测行为的差异，这表明扩散存在界面阻碍，可能是由于互穿网络的形成。最后，监测了两种染料以不同速率从PEG/PHEMA多层层合物中同时释放的情况，以证明CLSM在理解凝胶装置中溶质分布的复杂时间变化方面的有用性。
