Optimizing The Fabrication Of Shape-Defined Microparticles For Sustained Drug Delivery: The 'Less Is More' Paradigm

Polymeric microparticles find extensive use in several pharmaceutical applications. Our group has developed poly(lactic-co-glycolic acid) (PLGA) microPLates (μPL) featuring a square base of 20 × 20 μm and a height of 10 μm for the controlled and sustained delivery of a range of therapeutic payloads, including anti-inflammatory and anti-cancer drugs, small molecules for neurodevelopmental disorders, and siRNA for osteoarthritis. In this study, the morphological and pharmacological properties of PLGA-μPL were optimized by introducing new steps in the original fabrication protocol and systematically varying the polymer content. Vacuum suction was used to control solvent removal, and two different "cleaning" steps were tested, resulting in six different μPL configurations with a PLGA content ranging from 2 to 10 mg. Electron and optical microscopy analyses confirmed the well-defined square shape of μPL, with a central concavity depending on the PLGA content. Fabrication yielding ranged between 10% and 70%, while encapsulation efficiencies reached approximately 15% using curcumin (CURC) as a model drug. The kinetics of CURC release was analyzed using the semi-empirical model of Korsmeyer-Peppas, suggesting either a Fickian diffusion or anomalous transport mechanisms based on the PLGA amounts. Complementary techniques were used to assess morphological alterations and mass loss, evaluating the degradation μPL over time in water and physiological solutions. Unexpectedly, μPL configurations with lower PLGA contents exhibited higher fabrication yielding, drug encapsulation, and slower drug release. The optimized fabrication approach offers greater flexibility to tailor the degradation and pharmacological properties of μPL for various therapeutic applications.