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Effects of the hydrophobization on chitosan-insulin nanoparticles obtained by an alkylation reaction on chitosan

机译:疏水化对壳聚糖烷基化反应制得的壳聚糖-胰岛素纳米颗粒的影响

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In this work, we investigate the influence of chitosan hydrophobization on the formation, physicochemical properties, solubilization, and release profiles of chitosan-based nanoparticles (NPs) complexed with the protein insulin, used as a protein model. We use an alkylation procedure to insert 8, 10, and 12 carbon chains along the chitosan macromolecule with a final 5, 10, or 50% substitution degree. Nuclear magnetic resonance (NMR) and infrared spectroscopes (IR) were used to evaluate the success and extent of the hydrophobization procedure. The size, shape, and charge of bare polymer and polymer-insulin NPs were evaluated by dynamic light scattering (DLS), transmission electron (TEM), and atomic force (AFM) microscopes, and zeta potential, respectively. DLS and zeta potential data demonstrated that polymeric NPs made with hydrophobized chitosans possess smaller sizes and higher positive charges than NPs obtained with unmodified chitosan. Also, TEM and AFM images showed that modified chitosan-made NPs have more elongated structures. Isothermal titration calorimetry (ITC) was used to determine the type and extent of the existing interactions between the different constituting components of complexed insulin-hydrophobized chitosan nanoparticles. The association efficiency and loading capacity of insulin into the polymeric nanoparticles were also investigated under different solution conditions. Our results showed that hydrophobized chitosan-based NPs possess both higher association efficiencies and protein loading capacities at pH 6 in comparison with unmodified chitosan-based ones. In vitro protein release studies at pH 5.3, 6, and 7.4 demonstrated that insulin is released more slowly from hydrophobized chitosan NPs, which would favor a more sustained protein release.
机译:在这项工作中,我们调查了壳聚糖疏水化对与蛋白胰岛素复合的壳聚糖基纳米颗粒(NPs)的形成,理化性质,溶解和释放曲线的影响,该蛋白用作蛋白模型。我们使用烷基化程序沿壳聚糖大分子插入8、10和12个碳链,最终取代度为5%,10%或50%。核磁共振(NMR)和红外光谱仪(IR)用于评估疏水化程序的成功程度和程度。裸露的聚合物和聚合物-胰岛素NP的大小,形状和电荷分别通过动态光散射(DLS),透射电子(TEM)和原子力(AFM)显微镜以及zeta电位进行评估。 DLS和zeta电位数据表明,与未修饰的壳聚糖获得的NP相比,用疏水化壳聚糖制备的聚合物NP具有更小的尺寸和更高的正电荷。此外,TEM和AFM图像显示,改性壳聚糖制成的NP具有更长的结构。等温滴定热法(ITC)用于确定复合的胰岛素-疏水化壳聚糖纳米粒子的不同构成成分之间现有相互作用的类型和程度。还研究了在不同溶液条件下胰岛素在聚合物纳米颗粒中的缔合效率和负载能力。我们的结果表明,与未修饰的壳聚糖基纳米粒子相比,疏水化的壳聚糖基纳米粒子在pH 6下具有更高的缔合效率和蛋白质负载能力。在pH值为5.3、6和7.4的体外蛋白质释放研究表明,胰岛素从疏水化壳聚糖NPs释放的速度较慢,这有利于蛋白质的持续释放。

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