Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, Nagyerdei St. 98, H-4032 Debrecen, Hungary.
Department of Histology, Faculty of Medicine, 'Vasile Goldiș' Western University of Arad, 86 Rebreanu Street, 310414 Arad, Romania.
Biomolecules. 2019 Sep 20;9(10):509. doi: 10.3390/biom9100509.
2-Hydroxypropyl-beta-cyclodextrin (HPBCD) is utilized in the formulation of pharmaceutical products and recently orphan designation was granted for the treatment of Niemann-Pick disease, type C. The exact mechanism of HPBCD action and side effects are not completely explained. We used fluorescently labelled hydroxypropyl-beta-cyclodextrin (FITC-HPBCD) to study its pharmacokinetic parameters in mice and compare with native HPBCD data. We found that FITC-HPBCD has fast distribution and elimination, similar to HPBCD. Interestingly animals could be divided into two groups, where the pharmacokinetic parameters followed or did not follow the two-compartment, first-order kinetic model. Tissue distribution studies revealed, that a significant amount of FITC-HPBCD could be detected in kidneys after 60 min treatment, due to its renal excretion. Ex vivo fluorescent imaging showed that fluorescence could be measured in lung, liver, brain and spleen after 30 min of treatment. To model the interaction and cellular distribution of FITC-HPBCD in the wall of blood vessels, we treated human umbilical vein endothelial cells (HUVECs) with FITC-HPBCD and demonstrated for the first time that this compound could be detected in the cytoplasm in small vesicles after 30 min of treatment. FITC-HPBCD has similar pharmacokinetic to HPBCD and can provide new information to the detailed mechanism of action of HPBCD.
2-羟丙基-β-环糊精（HPBCD）被用于药物制剂的配方中，最近因其治疗尼曼-皮克病 C 型的作用被授予孤儿药地位。HPBCD 的作用机制和副作用尚不完全清楚。我们使用荧光标记的羟丙基-β-环糊精（FITC-HPBCD）研究其在小鼠中的药代动力学参数，并与天然 HPBCD 数据进行比较。我们发现 FITC-HPBCD 的分布和消除速度很快，与 HPBCD 相似。有趣的是，动物可以分为两组，其中药代动力学参数遵循或不遵循二室、一级动力学模型。组织分布研究表明，在 60 分钟治疗后，由于肾脏排泄，大量的 FITC-HPBCD 可以在肾脏中检测到。离体荧光成像显示，在 30 分钟治疗后，可以在肺、肝、脑和脾中测量到荧光。为了模拟 FITC-HPBCD 在血管壁中的相互作用和细胞分布，我们用 FITC-HPBCD 处理人脐静脉内皮细胞（HUVECs），并首次证明该化合物在 30 分钟治疗后可以在细胞质中小泡中检测到。FITC-HPBCD 的药代动力学与 HPBCD 相似，可以为 HPBCD 的作用机制提供新的信息。
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