Microfluidic Engineering of Core–Shell PLGA Microspheres with Adjustable Shell Thickness for Long-Acting Delivery of Leuprolide Acetate

ratio was adjusted from 1 to 6 to yield PLGA microspheres of different core-shell structures. HPLC was employed to determine the LA concentration within microspheres and evaluate their long-term release behavior. It was shown that uniform microspheres of 80 μm with distinct core-shell structure were formed using this device, and shell thickness was successfully regulated via the control of the flow rate ratios. The increases in shell thickness significantly enhanced the encapsulation efficiency (EE) (from 65.48% to 87.66%), reduced the initial burst release (from 59.24% to 23.52%), and prolonged the sustained-release duration from approximately 30 to 70 days. Under the appropriate thickness, the LA concentration could also function to improve the encapsulation properties. Overall, this work provides mechanistic insight into the structure-performance relationship of microfluidic manipulated core-shell PLGA microspheres for long-term release of LA and establishes a rational foundation for the design of predictable long-acting peptide delivery systems.