School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
Small. 2010 May 7;6(9):1003-11. doi: 10.1002/smll.200901985.
Particulate systems have tremendous potential to achieve controlled release and targeted delivery of drugs. However, conventional single-layered particles have several inherent limitations, including initial burst release, the inability to provide zero-order release, and a lack of time-delayed or pulsatile release of therapeutic agents. Multilayered particles have the potential to overcome these disadvantages. Herein, it is shown how triple-layered polymeric microparticles can be fabricated through a simple, economical, reliable, and versatile one-step solvent evaporation technique. Particle morphologies and layer configurations are determined by scanning electron microscopy, polymer dissolution tests, and Raman mapping. Key fabrication parameters that affect the formation of triple-layered polymeric microparticles comprising poly(DL-lactide-co-glycolide) (50:50), poly(L-lactide), and poly(ethylene-co-vinyl acetate) (40 wt% vinyl acetate) are discussed, along with their formation mechanisms. Layer thickness and the configurations of these microparticles are altered by changing the polymer mass ratios. Finally, it is shown that drugs can be localized in specific layers of the microparticles. This fabrication process can therefore be used to tailor microparticle designs, thus allowing such "designer" particulate drug-delivery systems to function across a wide range of applications.
颗粒系统具有实现药物控制释放和靶向传递的巨大潜力。然而，传统的单层颗粒具有几个固有的局限性，包括初始突释、无法提供零级释放以及缺乏治疗剂的时滞或脉冲释放。多层颗粒有可能克服这些缺点。本文展示了如何通过一种简单、经济、可靠和通用的一步溶剂蒸发技术来制备三层聚合物微球。通过扫描电子显微镜、聚合物溶解测试和拉曼映射来确定颗粒形态和层结构。讨论了影响由聚（DL-丙交酯-共-乙交酯）（50:50）、聚（L-丙交酯）和聚（乙烯-共-醋酸乙烯酯）（40wt%醋酸乙烯酯）组成的三层聚合物微球形成的关键制造参数及其形成机制。通过改变聚合物的质量比，可以改变层厚度和这些微球的构型。最后，表明药物可以定位在微球的特定层中。因此，这种制造工艺可用于定制微球设计，从而使这些“设计”的颗粒药物递送系统能够在广泛的应用中发挥作用。
