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用于胰岛素有效口服递送的菊粉纳米载体的开发:合成、优化、表征及生物物理研究。

Development of inulin nanocarrier for effective oral delivery of insulin: synthesize, optimization, characterization, and biophysical study.

作者信息

Rasjava Achmad Ramadhanna'il, Kurniawati Desy, Rizki Wa Ode Sri, Kurniati Neng Fisheri, Hertadi Rukman

机构信息

Biochemistry and Biomolecular Engineering Research Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Bandung, Indonesia.

Pharmacology - Clinical Pharmacy Research Division, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia.

出版信息

J Biomater Sci Polym Ed. 2025 Jun;36(8):963-986. doi: 10.1080/09205063.2024.2436297. Epub 2024 Dec 4.

Abstract

The susceptibility of insulin against gastric acid degradation presents a major challenge for oral insulin delivery. The potential of biopolymer-based nanocarriers was investigated in order to address this issue. Inulin, a biopolymer produced by the halophilic bacterium Salinivibrio sp. GM01, has been evaluated for its effectiveness as an insulin nanocarrier. Using central composite design (CCD) method, the optimum condition of inulin-encapsulated insulin (I-In) was achieved at 53 mg of inulin stirred at 17,800 rpm for 10 min, resulting in spherical I-In nanoparticles (I-In NPs) with an average diameter of 416 ± 32 nm and encapsulation efficiency of 87.04 ± 3.01%. The insulin release profile of I-In NPs in simulated gastric fluid follows a burst pattern. Biophysical analysis revealed that insulin in I-In NPs had higher conformational stability than the free state (FS) insulin, as evidenced by an increase in denaturation half-life up to 60 min and the transition enthalpy by 0.29 and 1.53 kcal/mol for secondary and tertiary structures, respectively. Furthermore, preliminary studies showed that I-In NPs showed significant effect compared to FS insulin for up to 15% in blood glucose level reduction. This study demonstrates the potential of I-In NPs as a promising candidate for antidiabetic therapy and an effective oral delivery system.

摘要

胰岛素对胃酸降解的敏感性给口服胰岛素递送带来了重大挑战。为了解决这个问题,研究了基于生物聚合物的纳米载体的潜力。菊粉是一种由嗜盐细菌盐弧菌属GM01产生的生物聚合物,已被评估作为胰岛素纳米载体的有效性。采用中心复合设计(CCD)方法,在53毫克菊粉以17,800转/分钟搅拌10分钟的条件下,实现了菊粉包封胰岛素(I-In)的最佳条件,得到平均直径为416±32纳米、包封效率为87.04±3.01%的球形I-In纳米颗粒(I-In NPs)。I-In NPs在模拟胃液中的胰岛素释放曲线呈现出突释模式。生物物理分析表明,I-In NPs中的胰岛素比游离态(FS)胰岛素具有更高的构象稳定性,二级和三级结构的变性半衰期分别增加到60分钟,过渡焓分别增加0.29和1.53千卡/摩尔,这证明了这一点。此外,初步研究表明,与FS胰岛素相比,I-In NPs在降低血糖水平方面有显著效果,最多可降低15%。这项研究证明了I-In NPs作为抗糖尿病治疗的有前途的候选者和有效的口服递送系统的潜力。

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