A novel pellets/thermosensitive hydrogel depot with low burst release for long-term continuous drug release: Preparation, characterization, in vitro and in vivo studies

The purpose of this study was to develop a pellets/thermosensitive gel hybrid depot (Pellets-Gel), designed to provide a novel implant delivery system for long-term steady controlled release of poor soluble drug with less burst release. Pellets made from PLGA and PEG loaded with curcumin (CUR-Pellets)were fabricated via combination of solvent evaporation and extrusion spheronization technique and were characterized by the appearance, drug loading (DL), structure, thermal behavior and morphology. The sol-gel conversion properties, polymers degradation characteristics, drug release kinetics in vitro of final optimized CUR loaded Pellets-Gel (CUR-Pellets-Gel) were evaluated, in vivo pharmacokinetics study were also performed on Sprague-Dawley rats. The results demonstrated that pellets with a diameter about 1.0 mm has a high loading capacity of CUR (30% (w/w)) can be simply produced. In in vitro study, CUR-Pellets-Gel showed a low burst release (2.67%) and release completeness up to 91.83%. In the pharmacokinetics study, the in vivo burst release of CUR-Pellets-Gel was significantly decreased reflected by the AUC (0-1d)/AUC (0-td) value. CUR-Pellets-Gel showed a smoother plasma drug level with a longer drug release profile for 78 days. These results demonstrated that this hybrid depot of pellets/thermosensitive gel could be more potential application in enhanced therapeutic effects of poor soluble drugs by continuously delivering for long periods of time without burst release. [Display omitted]