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基于天然生物活性生物相容性聚合物的胰岛素新型药物递送系统的研制。

Formulation of new drug delivery systems for insulin from natural bioactive biocompatible polymers.

作者信息

Fetouh Howida A, Aleem Engy E A, Mohammed Najiyah H, Aldesouky Jihad M Abd-Almajeed, Ismail Amel M

机构信息

Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.

Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.

出版信息

Sci Rep. 2025 Jan 31;15(1):3941. doi: 10.1038/s41598-025-86938-4.

Abstract

New insulin drug delivery systems (IDDs): insulin@chitin; insulin@chitin-grafted (g)-guar gum were prepared by using a modified sol-gel method. Insulin vials were loaded on the safe natural inert bioactive polymers (chitin and chitin-g-GG copolymer) carriers using water green solvent. Traces amount additives were below toxicity limits. Guar gum increased the numbers of the functional groups of the polymer carrier. Insulin release monitored at 37 ± 0.5 °C and buffer solutions of pH (1.2, 6.8 and 7.4) simulating physiological body fluids: stomach, intestine colon and blood stream. Insulin released from insulin@chitin only at pH 7.4. No release observed at pH 1.2, 6.8 due strong bonding to acetyl group of chitin. Insulin@chitin-GG system showed sustained targeting insulin-release at pH: 6.8 > 7.4 > 1.2. Release data obeyed pseudo second order kinetic model indicating that IDDs is heterogeneous solid surface of energetically different active sites. Each insulin molecule occupied two active sites. The slow release at pH 1.2 indicated protection against stomach juice. Release kinetic depend on physicochemical characteristics (porosity, swelling ratio as well as peptide and amino acid sequence). Both IDDs showed negative zeta potential indicating stability against aggregation. Gaur gum improved particle size distribution and insulin release.

摘要

新型胰岛素药物递送系统(IDDs):胰岛素@几丁质;胰岛素@几丁质接枝(g)-瓜尔胶通过改良的溶胶-凝胶法制备。使用水绿色溶剂将胰岛素小瓶装载到安全的天然惰性生物活性聚合物(几丁质和几丁质-g-GG共聚物)载体上。痕量添加剂低于毒性限度。瓜尔胶增加了聚合物载体的官能团数量。在37±0.5°C以及模拟生理体液(胃、小肠、结肠和血流)的pH值为(1.2、6.8和7.4)的缓冲溶液中监测胰岛素释放。胰岛素仅在pH值为7.4时从胰岛素@几丁质中释放。在pH值为1.2、6.8时未观察到释放,因为与几丁质的乙酰基团有强键合。胰岛素@几丁质-GG系统在pH值为6.8>7.4>1.2时显示出持续的靶向胰岛素释放。释放数据符合伪二级动力学模型,表明IDDs是具有能量不同活性位点的非均相固体表面。每个胰岛素分子占据两个活性位点。在pH值为1.2时的缓慢释放表明对胃液有保护作用。释放动力学取决于物理化学特性(孔隙率、溶胀率以及肽和氨基酸序列)。两种IDDs均显示出负的zeta电位,表明对聚集具有稳定性。瓜尔胶改善了粒径分布和胰岛素释放。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d569/11785760/9625d8e73971/41598_2025_86938_Fig1_HTML.jpg

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