采用流聚焦玻璃微流控器件制备用于药物输送的结构可生物降解聚合物微球。

Structured Biodegradable Polymeric Microparticles for Drug Delivery Produced Using Flow Focusing Glass Microfluidic Devices.

机构信息

Department of Chemical Engineering, Loughborough University , Loughborough, LE11 3TU, United Kingdom.

School of Energy, Environment & Agrifood (SEEA), Department of Offshore, Process & Energy Engineering, Cranfield University , Cranfield, MK43 0AL, United Kingdom.

出版信息

ACS Appl Mater Interfaces. 2015 Oct 21;7(41):23132-43. doi: 10.1021/acsami.5b06943. Epub 2015 Oct 12.

Abstract

Biodegradable poly(DL-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microparticles with tunable size, shape, internal structure and surface morphology were produced by counter-current flow focusing in axisymmetric (3D) glass capillary devices. The dispersed phase was composed of 0.5-2 wt % polymer solution in a volatile organic solvent (ethyl acetate or dichloromethane) and the continuous phase was 5 wt % aqueous poly(vinyl alcohol) solution. The droplets with a coefficient of variation in dripping regime below 2.5% were evaporated to form polymeric particles with uniform sizes ranging between 4 and 30 μm. The particle microstructure and surface roughness were modified by adding nanofiller (montmorillonite nanoclay) or porogen (2-methylpentane) in the dispersed phase to form less porous polymer matrix or porous particles with golf-ball-like dimpled surface, respectively. The presence of 2-4 wt % nanoclay in the host polymer significantly reduced the release rate of paracetamol and prevented the early burst release, as a result of reduced polymer porosity and tortuous path for the diffusing drug molecules. Numerical modeling results using the volume of fluid-continuum surface force model agreed well with experimental behavior and revealed trapping of nanoclay particles in the dispersed phase upstream of the orifice at low dispersed phase flow rates and for 4 wt % nanoclay content, due to vortex formation. Janus PLA/PCL (polycaprolactone) particles were produced by solvent evaporation-induced phase separation within organic phase droplets containing 3% (v/v) PLA/PCL (30/70 or 70/30) mixture in dichloromethane. A strong preferential adsorption of Rhodamine 6G dye onto PLA was utilized to identify PLA portions of the Janus particles by confocal laser scanning microscopy (CLSM). Uniform hemispherical PCL particles were produced by dissolution of PLA domes with acetone.

摘要

可生物降解的聚(DL-乳酸)(PLA)和聚(乳酸-共-羟基乙酸)(PLGA)微米粒子具有可调节的尺寸、形状、内部结构和表面形态,是通过在轴对称(3D)玻璃毛细管装置中使用逆流流动聚焦法制备的。分散相由 0.5-2wt%聚合物在挥发性有机溶剂(乙酸乙酯或二氯甲烷)中的溶液组成,连续相为 5wt%水性聚乙烯醇溶液。在滴落模式下,变化系数低于 2.5%的液滴被蒸发,形成尺寸均匀的聚合物粒子,尺寸范围在 4 到 30μm 之间。通过在分散相中添加纳米填料(蒙脱土纳米粘土)或致孔剂(2-甲基戊烷)来改变粒子的微观结构和表面粗糙度,分别形成具有较少多孔聚合物基质或具有高尔夫球状凹坑表面的多孔粒子。在主体聚合物中添加 2-4wt%纳米粘土可显著降低扑热息痛的释放速率,并防止早期突释,这是由于聚合物孔隙率降低和扩散药物分子的曲折路径所致。使用体积流-连续表面力模型的数值模拟结果与实验行为吻合较好,并揭示了在低分散相流速下,由于涡旋形成,纳米粘土颗粒在孔口上游的分散相被捕获,对于 4wt%纳米粘土含量更是如此。在含有 3%(v/v)PLA/PCL(30/70 或 70/30)混合物的二氯甲烷中的有机相液滴内通过溶剂蒸发诱导相分离制备了 Janus PLA/PCL(聚己内酯)粒子。利用 Rhodamine 6G 染料对 PLA 的强优先吸附,通过共聚焦激光扫描显微镜(CLSM)来识别 Janus 粒子的 PLA 部分。通过丙酮溶解 PLA 圆顶,制备出均匀的半球形 PCL 粒子。

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