Pharmacokinetics, biodistribution, and bioavailability of gossypol-loaded Pluronic® F127 nanoparticles

To enhance the water solubility and improve the bioavailability of gossypol, gossypol-loaded Pluronic (R) F127 nanoparticles (GLPFNs) for intravenous (i.v.) administration were prepared through thin-film hydration. The morphological characteristics of the GLPFNs were determined by transmission electron microscopy and particle size analysis. Pharmacokinetic and biodistribution studies were performed using Kun Ming (KM) mice by measuring gossypol concentrations in plasma and tissue samples of the mice using ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC- ESI-MS/MS). The GLPFNs exhibited uniform spherical shapes with a dynamic size of 70 +/- 2.4 nm. The encapsulation and drug-loading efficiencies of the GLPFNs were 91.2% +/- 3.1% and 9.1% +/- 0.42%, respectively. The particles further exhibited sustained drug release for about 200 h. The UHPLC-ESI-MS/MS method used in this work for plasma and tissue sample analysis was fully validated. The pharmacokinetics of the GLPFNs was studied after intravenous (i.v.) and intragastric (i.g.) administration to KM mice, and tissue distribution studies of the GLPFNs were performed. The AUC (0-inf) of the GLPFNs exhibited five- and sixfold increases. The clearance of GLPFNs decreased up to 5.6-fold when the gossypol entrapped in GLPFNs was i.g. administered. The absolute bioavailability of GLPFNs, which was 44.32%, increased by threefold compared with that of gossypol alone. The relative bioavailability of the GLPFNs after intravenous (i.v.) and intragastric (i.g.) administration was 192.38% and 560.75%, respectively. The concentration of GLPFNs was higher than that of gossypol, especially in reticuloendothelial cell-containing organs. Thus, the GLPFNs improved the bioavailability of the lipophilic drug gossypol. The gossypol-loaded Pluronic (R) F127 nanoparticles exhibited high biocompatibility and tunable drug release characteristics for treating cancer.