Enhancing drug release from PEG-PLGA implants: The role of Hydrophilic Dexamethasone Phosphate in modulating release kinetics and degradation behavior

Poly(lactic-co-glycolic acid) (PLGA) is a prominent biodegradable polymer used in biomedical applications, including drug delivery systems (DDS) and tissue engineering. PLGA's ability to control drug release is often hindered by nonlinear release profiles and slow initial drug release for hydrophobic drugs. This study investigates the incorporation of dexamethasone phosphate (DEXP) into polyethylene glycol–poly(lactic-co-glycolic acid) (PEG-PLGA) implants to enhance the initial release rate of dexamethasone (DEX). Implants were fabricated via hot-melt extrusion with varying DEX to DEXP ratios. X-ray diffraction (XRD) analysis confirmed that DEX remained crystalline in all formulations, whereas DEXP's crystallinity was detectable only in higher concentrations. Energy-dispersive X-ray spectroscopy (EDX) provided insights into the distribution of DEX and DEXP within the polymer matrix. Drug release studies revealed that PEG-PLGA implants accelerated initial drug release with increasing quantity of DEXP, though it also led to a shorter overall release duration. Despite these improvements, all implants exhibited a biphasic release profile. DEXP also influenced the characteristics of the polymer matrix, evidenced by increased swelling, water absorption, and mass loss. ¹H NMR analysis revealed a faster decrease in glycolic acid monomers in DEXP-containing implants. These findings demonstrate that DEXP enhances early drug release of DEX-loaded PEG-PLGA implants prepared by hot-melt extrusion. However, balancing initial and sustained release profiles remains challenging.