Jiwani Shahwar Imran, Huang Sha, Beji Oritsegidenene, Gyasi-Antwi Philemon, Gillis Richard B, Adams Gary G
University of Nottingham, Faculty of Medicine and Health Sciences, Queen's Medical Centre, Clifton Boulevard, Nottingham NG7 2HA, UK.
University of Nottingham, School of Biosciences, Sutton Bonington Campus, Sutton Bonington, Leicestershire LE12 5RD, UK.
Polymers (Basel). 2020 Feb 9;12(2):390. doi: 10.3390/polym12020390.
Protein polysaccharide complexes have been widely studied for multiple industrial applications and are popular due to their biocompatibility. Insulin degludec, an analogue of human insulin, exists as di-hexamer in pharmaceutical formulations and has the potential to form long multi-hexamers in physiological environment, which dissociate into monomers to bind with receptors on the cell membrane. This study involved complexation of two negatively charged bio-polymers xanthan and alginate with clinically-relevant insulin degludec (PIC). The polymeric complexations and interactions were investigated using biophysical methods. Intrinsic viscosity [η] and particle size distribution (PSD) of PIC increased significantly with an increase in temperature, contrary to the individual components indicating possible interactions. [η] trend was X > XA > PIC > A > IDeg. PSD trend was X>A>IDeg>XA>PIC. Zeta (ζ)- potential (with general trend of IDeg < A < XA < X ≈ PIC) revealed stable interaction at lower temperature which gradually changed with an increase in temperature. Likewise, sedimentation velocity indicated stable complexation at lower temperature. With an increase in time and temperature, changes in the number of peaks and area under curve were observed for PIC. Conclusively, stable complexation occurred among the three polymers at 4 °C and 18 °C and the complex dissociated at 37 °C. Therefore, the complex has the potential to be used as a drug delivery vehicle.
蛋白质多糖复合物已被广泛研究用于多种工业应用，并因其生物相容性而受到欢迎。德谷胰岛素是一种人胰岛素类似物，在药物制剂中以二聚六聚体形式存在，在生理环境中有可能形成长链多聚六聚体，然后解离成单体与细胞膜上的受体结合。本研究涉及两种带负电荷的生物聚合物黄原胶和海藻酸盐与临床相关的德谷胰岛素（PIC）的络合。使用生物物理方法研究了聚合物的络合和相互作用。PIC的特性粘度[η]和粒径分布（PSD）随温度升高而显著增加，这与单个组分相反，表明可能存在相互作用。[η]的趋势为X > XA > PIC > A > IDeg。PSD的趋势为X > A > IDeg > XA > PIC。zeta（ζ）电位（一般趋势为IDeg < A < XA < X ≈ PIC）表明在较低温度下存在稳定的相互作用，随着温度升高逐渐变化。同样，沉降速度表明在较低温度下存在稳定的络合。随着时间和温度的增加，观察到PIC的峰数和曲线下面积发生变化。总之，三种聚合物在4℃和18℃下发生稳定络合，络合物在37℃下解离。因此，该络合物有潜力用作药物递送载体。
