Xu Qiaobing, Hashimoto Michinao, Dang Tram T, Hoare Todd, Kohane Daniel S, Whitesides George M, Langer Robert, Anderson Daniel G
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachussets Avenue, Cambridge, MA 02139, USA.
Small. 2009 Jul;5(13):1575-81. doi: 10.1002/smll.200801855.
Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several therapies approved by the US Food and Drug Administration. Conventional emulsion-based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug-loaded microparticles from biodegradable polymers using the microfluidic flow-focusing (FF) devices and the drug-delivery properties of those particles. Particles are engineered with defined sizes, ranging from 10 microm to 50 microm. These particles are nearly monodisperse (polydispersity index = 3.9%). A model amphiphilic drug (bupivacaine) is incorporated within the biodegradable matrix of the particles. Kinetic analysis shows that the release of the drug from these monodisperse particles is slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibit a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release is attributed to the uniform distribution of the drug inside the particles generated using the microfluidic methods. These results demonstrate the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs.
可降解微粒作为药物递送载体具有广泛的用途，并且是美国食品药品监督管理局批准的几种疗法的基础。传统的基于乳液的制造方法在每一批中都会产生具有广泛直径范围（以及因此具有不同释放动力学）的颗粒。本文描述了使用微流控流动聚焦（FF）装置由可生物降解聚合物制备单分散、载药微粒及其药物递送特性。所制备的微粒尺寸确定，范围从10微米到50微米。这些微粒几乎是单分散的（多分散指数 = 3.9%）。一种模型两亲性药物（布比卡因）被纳入微粒的可生物降解基质中。动力学分析表明，这些单分散微粒中药物的释放比相同平均尺寸但尺寸分布更宽的传统方法制备的微粒慢，并且最重要的是，其初始突释比传统微粒显著更低。药物释放初始动力学的差异归因于使用微流控方法在微粒内部产生的药物均匀分布。这些结果证明了微流控流动聚焦在生成用于药物递送的均匀微粒系统方面的实用性。
