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胰岛素-PHBV 纳米粒/藻酸盐水凝胶复合系统的制备、表征及体外评价用于胰岛素的长效递送。

Preparation, Characterization and In vitro Evaluation of Insulin-PHBV Nanoparticles/Alginate Hydrogel Composite System for Prolonged Delivery of Insulin.

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Ziaeian Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Pharm Sci. 2024 Aug;113(8):2552-2559. doi: 10.1016/j.xphs.2024.03.010. Epub 2024 Mar 19.

Abstract

PURPOSE

In the present study, biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticles (NPs) containing insulin were loaded in sodium alginate/jeffamine (ALG/jeff) hydrogel for prolonged delivery of insulin. The main aim of this work was to fabricate an efficient insulin delivery system to improve patient adherence by decreasing the repetition of injections.

METHODS

Swelling and morphological properties and crosslinking efficiency of ALG/jeff hydrogel were assessed. The composite hydrogel was prepared by adding PHBV NPs to ALG/jeff hydrogel concurrently with crosslinking process. The morphology and loading capacity of composite hydrogel were analyzed.

RESULTS

Circular dichroism measurement demonstrated that insulin remains stable following fabrication process. The release profile exhibited 54.6 % insulin release from composite hydrogel within 31 days with minor initial burst release equated to nanoparticles and hydrogels. MTT cell viability analysis was performed by applying L-929 cell line and no cytotoxic effect was observed.

CONCLUSIONS

Favorable results clearly introduced fabricated composite hydrogel as an excellent candidate for drug delivery systems and also paves the route for prolonged delivery systems of other proteins.

摘要

目的

在本研究中,载有胰岛素的可生物降解聚(3-羟基丁酸酯-共-3-羟基戊酸酯)(PHBV)纳米颗粒(NPs)被负载于海藻酸钠/Jeffamine(ALG/Jeff)水凝胶中,以实现胰岛素的长效递送。这项工作的主要目的是构建一种有效的胰岛素递送系统,通过减少注射次数来提高患者的顺应性。

方法

评估了 ALG/Jeff 水凝胶的溶胀和形态特性以及交联效率。通过在交联过程中同时将 PHBV NPs 添加到 ALG/Jeff 水凝胶中来制备复合水凝胶。分析了复合水凝胶的形态和载药能力。

结果

圆二色谱测量表明,胰岛素在制备过程后保持稳定。释放曲线显示,复合水凝胶在 31 天内释放了 54.6%的胰岛素,初始突释较小,与纳米颗粒和水凝胶相当。通过 L-929 细胞系进行 MTT 细胞活力分析,未观察到细胞毒性。

结论

良好的结果清楚地表明,所制备的复合水凝胶是一种很有前途的药物递送系统候选物,也为其他蛋白质的长效递送系统铺平了道路。

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