pH-Responsive nanoparticles composed of chitosan (CS) and poly-gamma-glutamic acid (gamma-PGA) blended with tripolyphosphate (TPP) and MgSO(4) (multi-ion-crosslinked NPs) were prepared and characterized to determine their effectiveness in the oral delivery of insulin. Their counterparts without TPP and MgSO(4) (NPs) were used as a control. FT-IR and XRD results indicated that the spontaneous interaction between CS, insulin, gamma-PGA, MgSO(4) and TPP can form an ionically crosslinked network-structure, leading to the formation of nanoparticles. Multi-ion-crosslinked NPs were more compact than NPs, while their zeta potential values were comparable. During storage, multi-ion-crosslinked NPs suspended in deionized water were stable for at least 10 weeks. Multi-ion-crosslinked NPs had a superior stability over a broader pH range than NPs. In the in vitro release study, NPs failed to provide an adequate retention of loaded insulin in dissolution media compared to multi-ion-crosslinked NPs. Transepithelial-electrical-resistance and transport experiments demonstrated that multi-ion-crosslinked NPs significantly more effectively transported insulin than NPs; confocal visualization further validated the enhanced permeation of insulin via the paracellular pathway. The aforementioned results suggest that multi-ion-crosslinked NPs are a promising carrier for improved transmucosal delivery of insulin in the small intestine.

译文

制备了由壳聚糖 (CS) 和聚 γ-谷氨酸 (γ-PGA) 与三聚磷酸盐 (TPP) 和MgSO(4) (多离子交联np) 混合组成的pH响应纳米颗粒,并对其进行了表征,以确定其在胰岛素口服递送中的有效性。没有TPP和MgSO(4) (NPs) 的同类产品被用作对照。Ft-ir和XRD结果表明,CS,胰岛素,γ-PGA,MgSO(4) 和TPP之间的自发相互作用可以形成离子交联的网络结构,从而导致纳米颗粒的形成。多离子交联的np比np更紧凑,而其zeta电位值可比。在储存过程中,悬浮在去离子水中的多离子交联np稳定至少10周。与NPs相比,多离子交联的NPs在更宽的pH范围内具有优异的稳定性。在体外释放研究中,与多离子交联的np相比,NPs未能在溶解介质中充分保留负载的胰岛素。跨上皮电阻和转运实验表明,多离子交联的NPs比NPs更有效地转运胰岛素; 共聚焦可视化进一步验证了通过细胞旁途径增强的胰岛素渗透。上述结果表明,多离子交联的np是改善小肠中胰岛素经粘膜递送的有前途的载体。

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