Microfluidic Regulation of Core-Shell PLGA Microspheres for Sustained Release of Leuprolide Acetate

Microsphere formulations represent a promising drug delivery system for proteins and peptides with short half-lives as they effectively mitigate drug degradation in vivo. This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with leuprolide acetate (LA) using microfluidic technology and to investigate key factors that could have a significant effect on the LA encapsulation and loading. A glass capillary microfluidic device for a water-in-oil-in-water (W/O/W) emulsion system was developed. Gelatin (Gel) of varying concentrations was introduced in the internal aqueous phase, and different collecting solutions for W/O/W emulsions were investigated. The effect of the LA concentration in the inner phase was also explored. It was shown that LA-loaded PLGA microspheres (LA-PLGA-MS) by microfluidics were monodisperse with a uniform particle size of 80 μm and exhibited a distinguished core-shell structure. At a Gel concentration of 7.5 mg/mL, the microspheres reached a maximum encapsulation efficiency (EE) of 80.28% and a drug loading (DL) of 4.24%. The in vitro release could last for around 28 days. The DL of microspheres was found to be increased with the increase in LA concentration in the inner water phase. The incorporation of Gel within the inner water phase and the collecting solution with a suitable pH value were the main factors that affected the EE of microspheres. Briefly, LA-PLGA-MS could be successfully prepared and regulated using microfluidics and sustained LA release as monodispersed microsphere formulations. The developed technological strategy could provide a precise strategy and experimental reference for applications in delivery systems for water-soluble peptides and proteins.