Center for Molecular Metabolism , Nanjing University of Science & Technology , Nanjing 210094 , China.
Department of Oncology , The Johns Hopkins University School of Medicine , Baltimore , Maryland 21287 , United States.
J Agric Food Chem. 2018 Oct 10;66(40):10479-10489. doi: 10.1021/acs.jafc.8b02879. Epub 2018 Oct 1.
We present an improved type of food gum (salecan) based hydrogels for oral delivery of insulin. Structural hydrogel formation was assessed with Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. We found that the hydrogel modulus, morphology, and swelling properties can be controlled by varying the salecan dose during hydrogel formation. Insulin was introduced into the hydrogel using a swelling-diffusion approach and then further used a drug prototype. In vitro insulin release profiles demonstrated that the release of entrapped insulin was suppressed in acidic conditions but markedly increased at neutral pH. Cell viability and toxicity tests revealed that the salecan hydrogel constructs were biocompatible. Oral administration of insulin-loaded salecan hydrogels in diabetic rats resulted in a sustained decrease of fasting plasma glucose levels over 6 h postadministration. For nondiabetic animals, the relative pharmacological bioavailability of insulin was significantly larger (6.24%, p < 0.05) for insulin-loaded hydrogels compared to free insulin. These results encourage further development of salecan-based hydrogels as vehicles for controlled insulin delivery following oral administration.
我们提出了一种改良型的基于食品胶（岩藻依聚糖）的水凝胶，用于胰岛素的口服递送。通过傅里叶变换红外光谱、热重分析和 X 射线衍射评估了结构水凝胶的形成。我们发现，通过在水凝胶形成过程中改变岩藻依聚糖的剂量，可以控制水凝胶的模量、形态和溶胀性能。通过溶胀-扩散法将胰岛素引入水凝胶中，然后进一步使用药物原型。体外胰岛素释放曲线表明，在酸性条件下，包埋胰岛素的释放受到抑制，但在中性 pH 下显著增加。细胞活力和毒性试验表明，岩藻依聚糖水凝胶构建物具有生物相容性。在糖尿病大鼠中口服给予载胰岛素的岩藻依聚糖水凝胶后，在给药后 6 小时内可持续降低空腹血糖水平。对于非糖尿病动物，与游离胰岛素相比，载胰岛素水凝胶的胰岛素相对药效生物利用度显著更高（6.24%，p<0.05）。这些结果鼓励进一步开发基于岩藻依聚糖的水凝胶作为口服给予后控制胰岛素递送的载体。
