Development of an Innovative Nanosystem Based on Functionalized Albumin and Oxidized Gellan for the Synergistic Delivery of Curcumin and Temozolomide in the Treatment of Brain Cancer.

IF 5.3 3区化学 Q1 POLYMER SCIENCE

Gels Pub Date : 2025-09-03 DOI:10.3390/gels11090708

Camelia Elena Iurciuc Tincu, Gabriela Vochița, Daniela Gherghel, Cosmin-Teodor Mihai, Silvia Vasiliu, Ștefania Racoviță, Anca Niculina Cadinoiu, Corina Lenuța Logigan, Mihaela Hamcerencu, Florin Mitu, Marcel Popa, Lăcrămioara Ochiuz

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引用次数: 0

Abstract

Treating brain cancer remains challenging due to the blood-brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin and temozolomide (TMZ). Nanoparticle stability was enhanced by crosslinking with aldehyde groups from oxidized gellan (OG). The successful attachment of LMWP to HSA at the thiol group of Cys34 was confirmed through FT-IR and ¹H-NMR analyses. Most self-assembled nanoparticles were smaller than 200 nm in diameter. Curcumin showed higher encapsulation efficiency than TMZ. In vitro drug release was pH-dependent: curcumin released more at pH 7.4, while TMZ release was better at pH 4. Higher crosslinking degrees reduced drug release. Cytotoxicity assays on V79-4 (normal) and C6 (glioma) cell lines showed increased apoptosis and significantly lower IC₅₀ values for co-encapsulated formulations, indicating a synergistic effect. Curcumin's antioxidant activity was maintained and protected from UV degradation by the polymer matrix. The parallel artificial membrane permeability assay (PAMPA) confirmed that the functionalized formulations with co-encapsulated drugs could cross the BBB. Hemocompatibility studies indicated a favorable profile for intravenous use.

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基于功能化白蛋白和氧化结冷胶的创新纳米系统的开发，用于协同递送姜黄素和替莫唑胺治疗脑癌。

由于血脑屏障（BBB）和化疗的全身毒性，治疗脑癌仍然具有挑战性。本研究的重点是开发用低分子量鱼精蛋白修饰的人血清白蛋白（HSA）纳米颗粒，以改善血脑屏障的穿越，并实现姜黄素和替莫唑胺（TMZ）的靶向递送。通过与氧化结冷胶（OG）的醛基交联，提高了纳米颗粒的稳定性。通过FT-IR和1H-NMR分析证实了LMWP与Cys34巯基上的HSA的成功连接。大多数自组装纳米颗粒直径小于200 nm。姜黄素的包封率高于TMZ。体外释药呈pH依赖性，姜黄素在pH 7.4时释药较多，TMZ在pH 4时释药较好。较高的交联度降低了药物释放。对V79-4（正常）和C6（胶质瘤）细胞株的细胞毒性试验显示，共胶囊制剂增加了细胞凋亡，显著降低了IC50值，表明其具有协同作用。姜黄素的抗氧化活性在聚合物基质中得到维持和保护。平行人工膜透性试验（PAMPA）证实，共包封药物功能化制剂可以穿过血脑屏障。血液相容性研究表明静脉注射使用有利。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gels POLYMER SCIENCE-

CiteScore

4.70

自引率

19.60%

发文量

707

审稿时长

11 weeks

期刊介绍： The journal Gels (ISSN 2310-2861) is an international, open access journal on physical (supramolecular) and chemical gel-based materials. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the maximum length of the papers, and full experimental details must be provided so that the results can be reproduced. Short communications, full research papers and review papers are accepted formats for the preparation of the manuscripts. Gels aims to serve as a reference journal with a focus on gel materials for researchers working in both academia and industry. Therefore, papers demonstrating practical applications of these materials are particularly welcome. Occasionally, invited contributions (i.e., original research and review articles) on emerging issues and high-tech applications of gels are published as special issues.