Improved Method for Loading Leuprolide Peptide Into Slow-Release Microspheres

Preformed 50/50 PLGA-COOH microspheres were loaded with leuprolide acetate in 0.1 M HEPES buffer (pH 7.4). Parameters optimized included microsphere concentration in loading solution, duration of loading, inner water phase volume, and porosity. In vitro release was assessed over 1 month. A quasi-equilibrium absorption model was developed to predict encapsulation efficiency and loading.

Long-acting injectable peptide formulations are critical for patient compliance — monthly injections are far more manageable than daily ones. This work improves the manufacturing process for loading peptide drugs into microspheres, potentially making production more efficient and enabling new long-acting formulations for other therapeutic peptides that are currently limited to short-acting injections.

As peptide therapeutics proliferate (GLP-1 agonists, antimicrobial peptides, hormone analogs), the need for sophisticated controlled-release formulations grows. This study advances the fundamental understanding of how peptides interact with PLGA polymers and provides a generalizable framework that could accelerate development of long-acting formulations for the next generation of peptide drugs.

The study focused on leuprolide as a model peptide; other peptides with different charge, size, or solubility may behave differently. Only in vitro release was assessed — in vivo pharmacokinetics were not studied. The theoretical model assumes quasi-equilibrium binding, which may not hold for all peptide-polymer combinations. Scale-up from laboratory conditions to commercial manufacturing was not addressed.