Devaraji Vinod, Jayanthi Sivaraman
Computational Drug Design Lab, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology Vellore-632014 Tamil Nadu India
RSC Adv. 2023 Jul 6;13(29):20282-20297. doi: 10.1039/d3ra02845c. eCollection 2023 Jun 29.
Insulin administered orally has a limited therapeutic profile due to factors such as digestion enzymes, pH, temperature, and acidic conditions in the gastrointestinal tract. Type 1 diabetes patients are typically restricted to use intradermal insulin injections to manage their blood sugar levels as oral administration is not available. Research has shown that polymers could enhance the oral bioavailability of therapeutic biologicals, but traditional methods for developing suitable polymers are time-consuming and resource-intensive. Although computational formulations can be used to identify the best polymers more quickly. The true potential of biological formulations has not been fully explored due to a lack of benchmarking studies. Therefore, molecular modelling techniques were used as a case study in this research to determine which polymer is most compatible among five natural biodegradable polymers to address insulin stability. Specially, molecular dynamics simulations were conducted in order to compare insulin-polymer mixtures at different pH levels and temperatures. Hormonal peptide morphological properties were analyzed in body and storage conditions to assess stability of insulin with and without polymers. According to our computational simulations and energetic analyses, polymer cyclodextrin and chitosan maintain insulin stability the most effectively, while alginate and pectin are less effective relatively. Overall, this study contributes valuable insight into the role of biopolymers in stabilizing hormonal peptides in biological and storage conditions. A study such as this could have a significant impact on the development of new drug delivery systems and encourage scientists to utilize them in the formulation of biologicals.
由于胃肠道中的消化酶、pH值、温度和酸性条件等因素,口服胰岛素的治疗效果有限。1型糖尿病患者通常只能通过皮内注射胰岛素来控制血糖水平,因为无法口服给药。研究表明,聚合物可以提高治疗性生物制品的口服生物利用度,但开发合适聚合物的传统方法既耗时又耗费资源。虽然可以使用计算制剂来更快地识别最佳聚合物。由于缺乏基准研究,生物制剂的真正潜力尚未得到充分探索。因此,本研究将分子建模技术作为案例研究,以确定五种天然可生物降解聚合物中哪种聚合物与胰岛素的相容性最佳,从而解决胰岛素稳定性问题。具体而言,进行了分子动力学模拟,以比较不同pH值和温度下胰岛素与聚合物的混合物。在体内和储存条件下分析激素肽的形态特性,以评估有无聚合物时胰岛素的稳定性。根据我们的计算模拟和能量分析,聚合物环糊精和壳聚糖对胰岛素稳定性的维持效果最佳,而海藻酸盐和果胶的效果相对较差。总体而言,本研究为生物聚合物在生物和储存条件下稳定激素肽方面的作用提供了有价值的见解。这样的研究可能会对新型药物递送系统的开发产生重大影响,并鼓励科学家在生物制剂配方中使用它们。