Pharmacokinetic properties and in vitro enzyme activities of TPGS-modified arginine deiminase cyclodextrin lipid nanoparticles / 中国药理学通报

Aim To investigate the pharmacokinetic properties and in vitro enzyme activities of D-a-to- copherol polyethylene glycol 1000 succinate-modified arginine deiminase cyclodextrin lipid nanoparticles (ACLN). Methods The diacetylmonooxime-thiosem- icarbazide colorimetric method was used to determine the ADI enzyme activity, and the double reciprocal plot method was used to determine the enzyme Michae- lis constants. After the rats were given intravenously free ADI and ACLN, rat plasma samples were taken at different time points to determine the activity of ADI, and the time-enzyme activity curve would be drawn and the pharmacokinetic data analyzed by DAS 2. 1. 1. Re¬sults The optimum temperature for ADI and ACLN was 37 °C and the optimum pH was 6. 5. The Km val¬ ues of free ADI and ACLN were 0. 87 and 0. 74 mmol • L"1, respectively. The Vmai values of free ADI and ACLN were 53.28, 62.50 fjimol • L"' • min"1, re-spectively. The V

Release Characteristics and Pharmacokinetic Properties of Chitosan Coated Curcumin Ethosomes / 中国药学杂志

OBJECTIVE: To investigate the release characteristics in vitro of chitosan coated curcumin ethosomes (CMETS-CS) and its pharmacokinetics in rats. METHODS: The in vitro cumulative release rate of CMETS-CS in two different media (pH 1.2 HCl and pH 6.8 PBS solution) was investigated by dynamic dialysis. The release behavior was evaluated by similar factor method. After gastrointestinal administration, the plasma drug concentration at different time point was determined by high performance liquid chromatography (HPLC), and the average plasma concentration-time curve was drawn. The pharmacokinetic parameters, bioequivalence between CMETS-CS and CM were analyzed by DAS software. RESULTS: The cumulative release rates of CMETS-CS in pH 1.2 HCl and pH 6.8 PBS solution were (70.49±0.75)%, (73.90±0.52)%, respectively. Compared with CM, the CMETS-CS significantly increase the drug release.The release behavior of CMETS-CS in the two different release media was similar. After calculation, the area under the 0-72 h curve (AUC0-72 h), mean residence time (MRT0-72 h), peak concentration (ρmax) of CMETS-CS were 11.84, 5.45, 1.55 times than those of free curcumin (CM), respectively and its relative bioavailability of CMETS-CS was 1 111.32%. The bioequivalence of AUC0-72 hAUC0-∞ and tmax and in CMETS-CS and CM were not eligible, but bioequivalence of ρmax was eligible. CONCLUSION: Compared with free curcumin, CMETS-CS can improve the release behavior in vitro, significantly improve the oral bioavailability in rats, and there is not bioequivalence between CMETS-CS and CM.