Novel pH-Responsive Folic Acid-Conjugated Zein-Carboxymethyl Cellulose Nanoparticles for Enhanced and Controlled Curcumin Release

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmaceutical Innovation Pub Date : 2025-05-06 DOI:10.1007/s12247-025-09992-5

Merve Öztekin, Yeşim Sağ Açıkel

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引用次数: 0

Abstract

Purpose

The aim of this study is to develop a novel pH-sensitive drug delivery system by encapsulating curcumin (CR) in carboxymethyl cellulose (CMC)-coated zein (ZN) nanoparticles (NPs). In addition, this study aims to improve a tumour-specific drug delivery system by targeting NPs with folic acid.

Methods

ZN-NPs were prepared by an antisolvent precipitation technique. Zetasizer, TGA, FT-IR, XRD, SEM and DSC analyses were used in the characterisation studies of the NPs. The dialysis method was used to study the release of CR from CR-ZN-NPs and CR-ZN-CMC-NPs.

Results

The smallest average ZN-NPs size, 117.2 nm, was obtained with a ultrapure water/ethanol ratio of 10/90 and 0.2 g of ZN. The ZN-NPs size loaded with 1.5 mg of CR was found to be 184 nm. The optimum average ZN-CMC-NPs size was obtained as 277.5 nm with an ideal polydispersity index (0.230) and zeta potential value (-48.1 mV) at a ZN to CMC mass ratio of 1:3. The maximum CR encapsulation efficiency and loading capacity of CR-ZN-NPs containing 2.5 mg of CR were 51% and 0.64%, respectively. For CR-ZN-CMC-NPs, the maximum CR encapsulation efficiency and loading capacity were 70% and 0.58%, respectively. The cumulative release percentages of CR from CR-ZN-NPs and CR-ZN-CMC-NPs loaded with 1.5 mg of CR were 63.6% and 82.5%, respectively, after 72 h in pH 5.6 PBS buffer. Under pH 7.4 conditions, the cumulative CR release percentages from CR-ZN-NPs and CR-ZN-CMC-NPs were 90.6% and 92.1%, respectively, after 72 h. A more controlled, sustained, slower but slightly lower release of CR was obtained at pH 5.6 than at pH 7.4. CR release was slightly retarded by folic acid (FA) conjugation to CR-ZN-CMC-NPs. The release kinetics of CR from both CR-ZN-CMC-NPs and CR-ZN-NPs were best represented by the Higuchi and Korsmeyer-Peppas models, which suggests an "anomalous transport" mechanism.

Conclusion

The study demonstrates that CMC-coated ZN-NPs were used as an effective CR delivery system by providing optimal CR encapsulation efficiency and controlled release. The study suggests that this pH-responsive, biocompatible drug delivery system could be optimized for dual-drug combinations or synergistic effects in cancer therapy, providing a promising foundation for further research.

Graphical Abstract

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新的ph响应叶酸共轭玉米蛋白-羧甲基纤维素纳米颗粒增强和控制姜黄素的释放

目的利用羧甲基纤维素（CMC）包被的玉米蛋白（ZN）纳米颗粒（NPs）包裹姜黄素（CR），建立一种新的ph敏感给药系统。此外，本研究旨在通过叶酸靶向NPs来改善肿瘤特异性药物递送系统。方法采用抗溶剂沉淀法制备szn - nps。采用Zetasizer， TGA, FT-IR， XRD， SEM和DSC分析对NPs进行了表征研究。采用透析法研究CR- zn - nps和CR- zn - cmc - nps中CR的释放情况。结果在超纯水/乙醇比为10/90、添加0.2 g ZN的条件下，得到的ZN- nps平均尺寸最小，为117.2 nm。负载1.5 mg CR的ZN-NPs粒径为184 nm。当锌与CMC质量比为1:3时，锌-CMC- nps的最佳平均粒径为277.5 nm，理想的多分散性指数为0.230，zeta电位值为-48.1 mV。CR含量为2.5 mg的CR- zn - nps的最大CR包封率为51%，载CR量为0.64%。CR- zn - cmc - nps的CR包封效率和载量分别为70%和0.58%。CR- zn - nps和CR- zn - cmc - nps在pH 5.6的PBS缓冲液中处理72 h后，CR的累积释放率分别为63.6%和82.5%。在pH 7.4条件下，CR- zn - nps和CR- zn - cmc - nps在72 h后的CR累积释放率分别为90.6%和92.1%,pH 5.6条件下CR的释放比pH 7.4条件下更有控制、持续、缓慢但略低。叶酸（FA）与CR- zn - cmc - nps的结合略微延缓了CR的释放。CR- zn - cmc - nps和CR- zn - nps的CR释放动力学由Higuchi和Korsmeyer-Peppas模型最好地描述，这表明CR的“异常转运”机制。结论cmc包被ZN-NPs具有最佳的CR包被效率和控释能力，是一种有效的CR递送体系。该研究表明，这种ph响应性强、生物相容性好的药物传递系统可以优化为双药联合或协同治疗癌症，为进一步的研究提供了良好的基础。图形抽象

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

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.