Design of a zero-order sustained release PLGA microspheres for palonosetron hydrochloride with high encapsulation efficiency

Abstract Efficient encapsulation of hydrophilic drugs was substantially challenging when using emulsion solvent evaporation approach. The aim of present study was to design palonosetron hydrochloride-loaded PLGA microspheres (Pal-MS) with high encapsulation efficiency (EE) to sustain drug release for over several days. Pal-MS were prepared using emulsion-solvent evaporation method. Results showed that the pH of external phase could significantly affect the EE and the drug release rate of Pal-MS. By increasing the pH of external phase from 5.0 to 10.0, EE of Pal-MS increased from 55.64% to 94.33%. When the pH of external phase was 7.0, an ideal Pal-MS with EE of 86.51% and a zero-order drug release profile was obtained. The improved EE and drug release performance was proved to be associated with possible PLGA degradation, enhanced drug-PLGA interaction and reduced drug diffusion from organic phase to aqueous phase. After subcutaneous injection, such Pal-MS showed more steady drug plasma concentration (0.207∼1.238 ng/ml) over the entire 6-day in comparison with those of multiple-day-dosing intravenous palonosetron hydrochloride solution. It was concluded that Pal-MS were successfully designed by the adjustment of the pH of external phase and could be promising for preventing both acute and delayed chemotherapy-induced nausea and vomiting (CINV).