Microfluidic Technology Creates Uniform Microspheres for Month-Long Leuprolide Release

Researchers developed a glass capillary microfluidic device to generate water-in-oil-in-water (W/O/W) emulsions that solidified into PLGA microspheres. They systematically varied gelatin concentration in the internal aqueous phase, collecting solution composition, and leuprolide concentration to optimize encapsulation. Microsphere morphology was characterized for size uniformity and core-shell structure. In vitro drug release was measured over 28 days.

Current leuprolide microsphere products (like Lupron Depot) are made using conventional emulsification techniques that produce particles of varying sizes, which can lead to inconsistent drug release. Microfluidic manufacturing creates extremely uniform particles, potentially improving the predictability and consistency of drug delivery. This technology could be applied to many other peptide and protein drugs that need sustained release, advancing the field of injectable depot formulations.

Microsphere-based drug delivery is a mature but still improving field. The shift from batch emulsification to microfluidic production represents a manufacturing evolution that could yield more consistent, higher-quality products. For peptide drugs specifically — which are expensive and often require precise dosing — uniform microspheres could reduce waste, improve pharmacokinetics, and potentially reduce the frequency of injections. This study demonstrates a platform technology applicable beyond leuprolide to any water-soluble peptide or protein drug.

This is an in vitro study only — no animal testing was performed to confirm that the 28-day release profile translates to sustained drug levels in vivo. Microfluidic production rates are typically much slower than conventional methods, which could limit commercial scalability. The 80 μm particle size is relatively large for injection, and injectability was not assessed. Comparison with commercially available leuprolide microsphere products was not included.