Microfluidic Production of Uniform Microcarriers with Multicompartments through Phase Separation in Emulsion Drops

Abstract

Microfluidics has provided biodegradable microcarriers for sustained release of drugs, while allowing insignificant initial bursting. Here, we further engineer the microcarriers to have multiple compartments to release distinct drugs in a more controlled fashion. With a capillary microfluidic device, monodisperse emulsion drops containing two immiscible biocompatible polymers, one is biodegradable and the other is pH-responsive, are prepared, which undergo phase separation as the solvent in the drops is depleted. The emulsion drops finally form uniform microcarriers with distinct compartments. During the phase separation and consolidation, two model drugs with different hydrophobicity involved in the drops are spontaneously concentrated in their own compartments with higher affinity. The configuration of the microcarriers is exclusively selected from five different structures depending on the pair of polymers, pH of continuous phase, and organic solvent of emulsion drops; two of five have minimum interfacial energy, and the others are kinetically arrested. Microcarriers with each configuration provide their unique release behavior of the model drugs. These are potentially useful for choosing the release profile of multiple drugs suitable for specific diseases.