On-demand preparation of calcium alginate microspheres via piezoelectric microfluidics

Calcium alginate microspheres (CAMs) have attracted extensive attention as a novel drug carrier due to their cheapness, biodegradability, biocompatibility and nontoxicity. The existing preparation technologies of CAMs require complex process steps and involve multiple types of equipment, which are difficult to achieve the real-time and on-demand supply of microspheres in micro-reaction experiments. In this work, CAMs for prolonged drug release are prepared by the designed piezoelectric microfluidic devices using sodium alginate (NaAlg) and calcium chloride (CaCl₂). Specifically, the on-demand CAMs are synthesized timely by piezoelectric micro-jet followed by the transportation of piezoelectric micro-pump. Furthermore, various solution concentrations, main parameters of excitation signal and different nozzle diameters are evaluated in terms of size, morphology and drug release rate. The control method of CAMs’ size is obtained based on the multi-physics coupling analysis. Experimental results show that the doxorubicin hydrochloride loaded CAMs (DOX-CAMs) which can be prepared on demand, have excellent uniformity and dispersion, and the minimum average particle size is about 81.9 µm. The controlled drug release rate of DOX-CAMs reaches 83.2 % after 24 h. Moreover, the piezoelectric microfluidic devices and corresponding control methods may have potentials to be adapted for synthesizing other inorganic composite microspheres.