Microfluidic Technology Creates Uniform Microspheres for Month-Long Leuprolide Release | Research

The takeaway

Researchers used microfluidic technology to create uniform PLGA microspheres that released the peptide drug leuprolide steadily for about 28 days.

80.28% encapsulation
Maximum encapsulation efficiency for leuprolide in PLGA microspheres produced by microfluidic technology

What the researchers found

Using a glass capillary microfluidic device, researchers produced monodisperse PLGA microspheres with a uniform particle size of 80 μm and a distinct core-shell structure for leuprolide acetate delivery. At an optimal gelatin concentration of 7.5 mg/mL in the inner aqueous phase, microspheres achieved maximum encapsulation efficiency of 80.28% and drug loading of 4.24%.

The microspheres sustained leuprolide release for approximately 28 days in vitro. Drug loading increased proportionally with leuprolide concentration in the inner phase. Gelatin incorporation and collecting solution pH were identified as the critical factors controlling encapsulation efficiency.

Why it matters

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.

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

This is a materials science/pharmaceutical engineering study demonstrating proof of concept for a manufacturing technique. It provides strong in vitro data for the formulation approach but lacks in vivo validation.

When this study was published

Published in 2025, this is a very recent study reflecting the current state of microfluidic drug delivery technology.

The bigger picture

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.

Questions still open

Does the in vitro 28-day release profile translate to sustained therapeutic leuprolide levels in animal models?
Can microfluidic production be scaled up to commercially viable throughput for microsphere manufacturing?
How do these uniform microspheres compare to commercial Lupron Depot in terms of pharmacokinetics and bioavailability?

Common questions

What are microspheres and why are they used for peptide drugs?

Microspheres are tiny biodegradable spheres (about the width of a human hair) that encapsulate drugs inside a polymer shell. As the polymer slowly dissolves, it releases the drug over weeks to months. This is ideal for peptide drugs like leuprolide, which would otherwise be broken down in the body within hours and require daily injections. Instead, a single microsphere injection can maintain drug levels for a month.

How does microfluidic production differ from conventional methods?

Conventional methods mix large batches of ingredients together, producing microspheres of many different sizes. Microfluidic production uses precision channels to form one droplet at a time, creating particles that are almost identical in size and structure. This uniformity means every microsphere releases its drug at the same rate, making the overall drug delivery more predictable and consistent.

Read the original research

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

Langmuir : the ACS journal of surfaces and colloids, 41(27), 17893-17901

View on PubMed ↗Publisher’s paper ↗

Citation

Wei, Ruoxin; Dou, Jiaze; Wu, Yihui; Li, Jinjin; Cen, Lian; Xi, Zhenhao. (2025). Microfluidic Regulation of Core-Shell PLGA Microspheres for Sustained Release of Leuprolide Acetate.. Langmuir : the ACS journal of surfaces and colloids, 41(27), 17893-17901. https://doi.org/10.1021/acs.langmuir.5c01667