The Study of Tacrolimus-Loaded Polyion Complex Micelles for Oral Delivery

In the present study, polyion complex micelles based on pluronic F127-chitosan (F127-CS) and sodium deoxycholate (NaDC) were prepared to improve the oral absorption of tacrolimus (FK506) by increasing its aqueous solubility and enhancing its absorption in the gastrointestinal (GI) tract. FK506-loaded F127-CS/NaDC micelles were prepared by the thin film hydration method and had a high drug-loading capacity (8.93 +/- 1.47%) and a small particle size (55.77 +/- 2.23 nm). The low critical micelle concentration (2.65x10(-3) mol/L) and the stability test results indicated that F127-CS/NaDC micelles have an enhanced stability against the dilution of GI fluid or blood. Tests of cell uptake showed that F127CS/NaDC micelles exerted a comparable P-glycoprotein inhibition to verapamil. Compared with FK506 solution, the time to peak (t(max)) of FK506 in F127-CS/NaDC micelles decreased from 3 to 1 h and the half-life was prolonged from 16.09 h to 18.00 h. Moreover, drug-time area under the curve was increased by 39.3%, from 533.79 to 742.11 ng/mL.h, which indicated enhanced oral absorption of FK506 in FK506-loaded F127-CS/NaDC micelles. Furthermore, the immunosuppressive effect of FK506-loaded F127-CS/NaDC micelles in a rat liver transplantation model was better than that of FK506 solution. All these results showed that FK506-loaded F127-CS/NaDC micelles are a promising approach for oral delivery of FK506.