Hydrogel-containing PLGA microspheres of palonosetron hydrochloride for achieving dual-depot sustained release

Abstract

The aim of this study was to prepare palonosetron hydrochloride poly (D, l-lactic acid-co-glycolic acid) (PLGA) microspheres suitable for long-term administration. PLGA as the carrier material and the emulsion-solvent evaporation method were used to prepare three types of palonosetron hydrochloride or palonosetron microspheres: F1 palonosetron hydrochloride W/O/W hydrogel PLGA microspheres, F2 palonosetron O/W PLGA microspheres and F3 palonosetron S/W/O/W hydrogel PLGA microspheres. Among these, F1 showed the best sustained-release behavior, as well as a high drug loading (2.99%) and encapsulation efficiency (78.86%), and a long release period (60 days in vitro). The drug release in vitro was affected by the burst release of the drug and the degradation and erosion of PLGA, as well as being dependent on the properties of the hydrogel, which could make the release rate slower and more stable. In addition, the blood concentration in rats was steady (35.74–1.16 ng/mL) and prolonged (7 days). Meanwhile, the formulation could achieve dual-depot sustained release, whereby Pal dispersed in the PLGA matrix in the early stage diffused to form the first peak at the 12th hour, while Pal concentrated in the hydrogel matrix diffused in the later stage to form the second peak on day 2. Furthermore, this formulation exhibited the best biocompatibility. Thus, W/O/W PLGA microspheres containing a temperature-sensitive hydrogel in the inner water phase showed great potential for palonosetron hydrochloride delivery.