PLGA implants for controlled dexamethasone delivery: Impact of the polymer chemistry

The aim of this study was to better understand the impact of the chemistry of poly(lactic-co-glycolic acid) (PLGA) polymers on the resulting drug release kinetics from implants prepared by melting and molding. Dexamethasone was incorporated as the drug. The polymer molecular weight of the PLGA, lactic acid:glycolic acid ratio and type of end groups (ester versus free acid) were varied. The implants were characterized using optical macroscopy, SEM, X-ray powder diffraction, DSC, gravimetric monitoring of dynamic changes in the systems' dry and wet mass upon exposure to the release medium as well as drug release and pH measurements. Interestingly, the shape of the drug release profiles was similar in all cases: No noteworthy burst effect was observed. Dexamethasone release set on after a lag time, the length of which strongly depended on the PLGA chemistry: The lag time decreased with decreasing polymer molecular weight, increasing glycolic acid content and was shorter for -COOH end groups compared to ester end groups. In all cases, drug release set on as soon as a critical hydrophilicity and polymer molecular weight were reached and substantial system swelling started: The penetration of large amounts of water into the implants allowed for complete dexamethasone dissolution and relatively rapid diffusion of the dissolved drug molecules through a highly swollen PLGA gel up to 100% drug release.