Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia.
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.
Eur J Pharm Sci. 2017 Aug 30;106:1-9. doi: 10.1016/j.ejps.2017.05.041. Epub 2017 May 19.
The bile acid taurocholic acid (TCA) is endogenously produced, and has shown formulation-stabilising effects when incorporated into microcapsules containing potential antidiabetic drugs. This study aimed to develop and characterise TCA-microcapsules, and test their antidiabetic effects, in an animal model of Type 1 diabetes (T1D).
Using the polymer sodium alginate (SA), SA-microcapsules (control) and TCA-microcapsules (test) were prepared, and assessed for morphology, surface composition, chemical and thermal stability, swelling, buoyancy, mechanical, release and rheological properties. TCA-microcapsules were gavaged as a single dose (1.2mg/300g) to alloxan-induced diabetic rats, and blood glucose and TCA concentrations in serum, tissues (ileum, liver and pancreas) and faeces, were measured. One healthy and one diabetic group were used as control and gavaged SA-microcapsules.
TCA-microcapsules showed consistent size, TCA presence on surface and all layers of microcapsules, chemical and thermal stability, enhanced swelling, buoyancy and targeted-release properties and rheological analysis showed Non-Newtonian flow properties. TCA serum concentrations were lower in the healthy group, compared with the diabetic and diabetic-treated groups, but there was no significant difference between diabetic control and diabetic treated groups, in terms of TCA levels, and blood glucose concentrations.
The developed TCA-microcapsules showed good stability and release properties, but did not lower blood glucose levels in T1D, which suggests absence of insulin-mimetic effects, when using a single 1.2mg/rat oral dose.
胆酸牛磺胆酸（TCA）是内源性产生的，当掺入含有潜在抗糖尿病药物的微胶囊中时，显示出制剂稳定化作用。本研究旨在开发和表征 TCA 微胶囊，并在 1 型糖尿病（T1D）动物模型中测试其抗糖尿病作用。
使用聚合物海藻酸钠（SA），制备 SA 微胶囊（对照）和 TCA 微胶囊（测试），并评估其形态、表面成分、化学和热稳定性、溶胀、浮力、机械、释放和流变性能。将 TCA 微胶囊作为单剂量（1.2mg/300g）灌胃给链脲佐菌素诱导的糖尿病大鼠，并测量血清、组织（回肠、肝脏和胰腺）和粪便中的血糖和 TCA 浓度。使用一个健康组和一个糖尿病组作为对照，灌胃 SA 微胶囊。
TCA 微胶囊显示出一致的大小、表面和微胶囊所有层的 TCA 存在、化学和热稳定性、增强的溶胀、浮力和靶向释放特性以及流变分析显示出非牛顿流动特性。与糖尿病组和糖尿病治疗组相比，健康组的血清 TCA 浓度较低，但在糖尿病对照组和糖尿病治疗组之间，TCA 水平和血糖浓度没有显著差异。
开发的 TCA 微胶囊显示出良好的稳定性和释放特性，但在使用 1.2mg/大鼠单剂量口服时，并未降低 T1D 中的血糖水平，这表明不存在胰岛素模拟作用。
