Study On FK506-Dimethyl-β-Cyclodextrin Inclusion Compound And Its Albumin Nanopreparation

Tacrolimus (FK506) is a potent immunosuppressant, but its poor solubility restricted its application. FK506-dimethyl-(3-cyclodextrin (DM-β-CD) inclusion compound was prepared by an ultrasonic method. Bovine serum albumin (BSA) nanoparticle (NP) was prepared by a desolvation-chemical crosslinking method. FK506-DM-β-CD-BSA NP was prepared and these experimental data for a novel drug delivery system were provided.FK506-DM-P-CD inclusion compound was prepared by grind method or ultrasonic method and the results indicated that ultrasonic method was better than grind method. Then, the inclusion compound formation condition optimized by orthogonal test was 0.5 h,40℃and 75% ethanol under ultrasound. The loading efficiency of inclusion compound prepared by the above conditions was (12.4±0.3)%, while the inclusion compound greatly improved the solubility of FK506.BSA NP was prepared using a desolvation-chemical crosslinking method. The effects of crosslinking time, pH, albumin concentration, and the volume of ethanol were investigated by a single factor test. The preparations were optimized with the morphology, particle size, and yield as the indexes. The degradation of albumin nanoparticles was evaluated in vitro. These results found that the controllable nanopartieles between 140 and 300 nm were prepared by altering ethanol volume. The NP was spherical with an average diameter of (148.4±7.9)nm, yield of (97.5±0.1)% with the preparation conditions as follows:albumin 50 mg/ml, pH 9, ethanol 4 ml, and 18 h for crosslinking. Degradation of the BSA NP was (81.9±0.4)% in artificial gastric juice after 15 min and (18.8±0.1)% in artificial intestinal juice after 24 h, respectively. Albumin nanopreparation was obtained with protective agent after freeze-drying.FK506-DM-P-CD-BSA NP was also prepared by a desolvation-chemical crosslinking method. When FK506 was chosen at 3.5 mg/ml, the entrapment efficiency and loading efficiency of FK506-DM-β-CD-BSA NP were (91.5±1.0)% and (3.20±0.04)%, respectively, its particle size was (245.2±7.5)nm. Comparing with FK506-BSA NP, FK506-DM-β-CD-BSA NP increased by 2.12% to 3.20% in loading efficiency, and decreased by degradation in enzyme. The cumulative release curves indicated that FK506-DM-β-CD-BSA NP had lower break-release and slower drug release. These results of pharmacokinetical study showed that it maintained stable blood drug level and held time longer for intravenous injection of FK506-DM-β-CD-BSA NP in rats. The absolute bioavailability of FK506-DM-β-CD-BSA NP was (117.6±3.5)%.