Smart swelling biopolymer microparticles by a microfluidic approach: Synthesis, in situ encapsulation and controlled release

This paper reports a microfluidic synthesis of biopolymer microparticles aiming at smart swelling. Monodisperse aqueous emulsion droplets comprising biopolymer and its cross-linking agent were formed in mineral oil and solidified in the winding microfluidic channels by in situ chaotic mixing, which resulted in internal chemical gelation for hydrogels. The achievement of pectin microparticles from in situ mixing pectin with its cross-linking agent, calcium ions, successfully demonstrates the reliability of this microfluidic synthesis approach. In order to achieve hydrogels with smart swelling, the following parameters and their impacts on the swelling behaviour, stability and morphology of microparticles were investigated: (1) the type of biopolymers (alginate or mixture of alginate and carboxymethylcellulose, A–CMC); (2) rapid mixing; (3) concentration and type of cross-linking agent. Superabsorbent microparticles were obtained from A–CMC mixture by using ferric chloride as an additional external cross-linking agent. The in situ encapsulation of a model protein, bovine serum albumin (BSA), was also carried out. As a potential protein drug-delivery system, the BSA release behaviours of the biopolymer particles were studied in simulated gastric and intestinal fluids. Compared with alginate and A–CMC microparticles cross-linked with calcium ions, A–CMC microparticles cross-linked with both calcium and ferric ions demonstrate a significantly delayed release. The controllable release profile, the facile encapsulation as well as their biocompatibility, biodegradability, mucoadhesiveness render this microfluidic approach promising in achieving biopolymer microparticles as protein drug carrier for site-specific release.