研究目的
To study the pharmacokinetic parameters of fluorescently labelled hydroxypropyl-beta-cyclodextrin (FITC-HPBCD) in mice and compare with native HPBCD data, and to investigate the interaction and cellular distribution of FITC-HPBCD in the wall of blood vessels.
研究成果
FITC-HPBCD has similar pharmacokinetic properties to HPBCD, although some deviation from the applied two-compartment model was found. The fast elimination, similar t1/2, Vd and tissue distribution show that FITC-HPBCD could be a suitable alternative model molecule to study and understand the pharmacological effect of HPBCD. The higher distribution in the lung can explain the pulmonary side effects of HPBCD, but on the other hand it may help to develop new targeting strategies.
研究不足
The in vivo fluorescence imaging experiments were not suitable to detect the real-time organ distribution of FITC-HPBCD in mice. FITC-HPBCD in the highly perfused skin capillaries gives a strong fluorescence signal from the skin of the animals, obscuring the signal of the organs from the deeper layer. Ex vivo organ measurements were needed to reveal the organ distribution of FITC-HPBCD.
1：Experimental Design and Method Selection
The study involved the synthesis of FITC-HPBCD, its administration to mice intravenously, and the collection of blood samples at various time points to determine pharmacokinetic parameters. The interaction of FITC-HPBCD with human umbilical vein endothelial cells (HUVECs) was also investigated.
2：Sample Selection and Data Sources
BALB/c male mice (23–25 g) were used for in vivo pharmacokinetic investigation. Human umbilical vein endothelial cells (HUVECs) were cultured for in vitro studies.
3：List of Experimental Equipment and Materials
FITC-HPBCD was synthesized by Cyclolab Ltd. (Budapest, Hungary). Other reagents were from Sigma-Aldrich (Budapest, Hungary). Equipment included a Zeiss Axio Scope.A1 fluorescence microscope, a FACScan flow cytometer, and a FLUOstar Optima microplate reader.
4：Experimental Procedures and Operational Workflow
Blood samples were collected from mice at specified times after FITC-HPBCD administration. Plasma concentrations were measured using a microplate reader. HUVECs were treated with FITC-HPBCD, and cellular uptake was analyzed by fluorescence microscopy and flow cytometry.
5：Data Analysis Methods
Pharmacokinetic parameters were calculated using SigmaStat software. Data are expressed as means ± SD. Comparison of groups was performed by ANOVA.
独家科研数据包，助您复现前沿成果，加速创新突破
获取完整内容
