Pharmacokinetics and Tissue Distribution of PLGAPLL-PEG-TF Nanoparticles Loaded with Daunorubicin and Tetrandrine Following Intravenous Injection in the Rats Using LC-MS/MS

  Objective: A sensitive, rapid and reliable LC-MS/MS method was developed for simultaneously determination of daunorubicin (DNR) and tetrandrine (Tet) in rat plasma and tissues. Methods: The pharmacokinetics and tissue distribution of DNR/Tet-PLGAPLL-PEG-NPs-Tf (D/T-PPP-NPs-Tf), DNR/Tet-PLGA-PLL-PEG-NPs (D/T-PPP-NPs) and DNR/Tet (D/T) solution were compared following intravenous injection in the rats. Result: Compare to D/T solution, the parameters of DNR and Tet in D/T-PPP-NPs-Tf group presented significantly higher AUC (p<0.01) and lower V (p<0.05). Compared with D/T solution, the distribution of DNR in groups of D/T-PPP-NPs and D/T-PPP-NPs-Tf were higher in liver (p<0.01), lung (p<0.05), fat (p<0.05) and testicle (p<0.05), and were lower in heart, spleen, kidney (p<0.01), brain and intestine (p<0.01). The distribution of Tet in D/T-PPP-NPs and D/T-PPP-NPs-Tf groups were higher in liver, brain and uterus (p<0.05), and were lower in heart, spleen, lung, kidney and fat (p<0.05) compared with D/T solution. Conclusion: The LC-MS/MS method was specific, sensitive, rapid and reliable for the simultaneously determination of DNR and Tet in rat plasma and tissues. Compared with D/T solution, D/T-PPP-NPs-Tf tended to stay in the blood after injection. The distribution of D/T-PPP-NPs and D/T-PPP-NPs-Tf were significantly changed.