Randall Christina L, Leong Timothy G, Bassik Noy, Gracias David H
Department of Biomedical Engineering, Johns Hopkins University, 720 Rutland Avenue, Baltimore MD 21205, USA.
Adv Drug Deliv Rev. 2007 Dec 22;59(15):1547-61. doi: 10.1016/j.addr.2007.08.024. Epub 2007 Sep 4.
Lithographic patterning offers the possibility for precise structuring of drug delivery devices. The fabrication process can also facilitate the incorporation of advanced functionality for imaging, sensing, telemetry and actuation. However, a major limitation of present day lithographic fabrication is the inherent two-dimensionality of the patterning process. We review a new approach to construct three dimensional (3D) patterned containers by lithographically patterning two dimensional (2D) templates with liquefiable hinges that spontaneously fold upon heating into hollow polyhedral containers. The containers have finite encapsulation volumes, can be made small enough to pass through a hypodermic needle, and the 3D profile of the containers facilitates enhanced diffusion with the surrounding medium as compared to reservoir systems fabricated in planar substrates. We compare the features of the containers to those of present day drug delivery systems. These features include ease of manufacture, versatility in size and shape, monodisperse porosity, ability for spatial manipulation and remote triggering to release drugs on-demand, the incorporation of electronic modules, cell encapsulation, biocompatibility and stability. We also review possible applications in drug delivery and cell encapsulation therapy (CET). The results summarized in this review suggest a new strategy to enable construction of "smart", three dimensional drug delivery systems using lithography.
光刻图案化技术为药物递送装置的精确结构化提供了可能性。制造过程还可以促进成像、传感、遥测和驱动等先进功能的整合。然而，当今光刻制造的一个主要限制是图案化过程固有的二维性。我们回顾了一种通过对具有可液化铰链的二维模板进行光刻图案化来构建三维（3D）图案化容器的新方法，这些铰链在加热时会自发折叠成中空多面体容器。这些容器具有有限的封装体积，可以做得足够小以通过皮下注射针，并且与在平面基板上制造的储库系统相比，容器的三维轮廓有助于增强与周围介质的扩散。我们将这些容器的特性与当今药物递送系统的特性进行了比较。这些特性包括易于制造、尺寸和形状的多样性、单分散孔隙率、空间操纵能力以及远程触发按需释放药物的能力、电子模块的整合、细胞封装、生物相容性和稳定性。我们还回顾了在药物递送和细胞封装治疗（CET）中的可能应用。本综述总结的结果表明了一种使用光刻技术构建“智能”三维药物递送系统的新策略。
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