PLGA microparticle-embedded thermosensitive hydrogels for sustained release of hydrophobic drugs

The release profile of a hydrophobic drug, indomethacin (IMC), from poly(lactic-co-glycolic acid) (PLGA) particles embedded in a chitosan-Pluronic (CP) hydrogel matrix was investigated. The PLGA particles were prepared by an oil-in-water (O/W) emulsion method, and were mixed with IMC. The average diameter of the prepared PLGA particles was determined as 41.6 +/- 35.8 microm by dynamic light scattering (DLS). The loading amount and loading efficiency were 0.023 +/- 0.01 mg/mg and 14.8 +/- 0.67%, respectively. The CP solution (16 wt%) was transformed into a thermosensitive hydrogel under increasing temperature above a lower critical solution temperature (LCST). In this process, the IMC-loaded PLGA particles were mixed and uniformly dispersed in the solution phase, following thermosensitive gelation. SEM observation revealed that the added IMC-loaded PLGA particles were uniformly dispersed in a three-dimensional matrix of the CP hydrogel, observed by SEM. The PLGA particles embedded in the CP hydrogel released about 30% of loaded IMC for 25 days, showing a significantly sustained release as compared with the PLGA particles only (approximately 50% for the same period). Therefore, it is assumed that this sustained release of IMC results from the retardation effect of the CP hydrogel matrix on the degradation and release of the PLGA particles.