Preparation, characterization and pharmacokinetic studies of tacrolimus-dimethyl-β-cyclodextrin inclusion complex-loaded albumin nanoparticles.
The purpose of the study is to develop a new formulation for clinically used anti-cancer agent tacrolimus (FK506) to minimize the severe side effects. Toward this end, a new formulation method has been developed by complexation of FK506 with an hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) using ultrasonic means. The resulting complex displays dramatically enhanced solubility of FK506. Then bovine serum albumin (BSA) nanoparticles were prepared directly from the preformed FK506/DM-β-CD inclusion complex by the desolvation-chemical crosslinking method, with the size of 148.4-262.9 nm. Stable colloidal dispersions of the nanoparticles were formed with zeta potentials of the range of -24.9 to -38.4 mV. The entrapment efficiency of FK506 was increased as high as 1.57-fold. Moreover, notably FK506 was released from the nanoparticles in a sustained manner. As demonstrated, pharmacokinetic studies reveal that, as compared with FK506-loaded BSA nanoparticles, the FK506/DM-β-CD inclusion complex-loaded BSA nanoparticles have significant increase at T(max), t(1/2), MRT and decrease at C(max). In summary, these results suggest that the drug/DM-β-CD inclusion complex-loaded BSA nanoparticles display significantly improved delivery efficiency for poorly soluble FK506 or its derivatives.
Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
Shanshan
S
Gao
Jun
J
Sun
Dongjun
D
Fu
Hongli
H
Zhao
Minbo
M
Lan
Feng
F
Gao
D000818:Animals; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents; D004563:Electrochemistry; D000431:Ethanol / Q000737:chemistry; D006207:Half-Life; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D016559:Tacrolimus / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
D003432:Cross-Linking Reagents; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; D012997:Solvents; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D012710:Serum Albumin, Bovine; D000431:Ethanol; D016559:Tacrolimus