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载姜黄素的玉米醇溶蛋白纳米颗粒:一种基于质量源于设计理念的增强药物递送及对癌细胞细胞毒性的方法。

Curcumin-loaded zein nanoparticles: A quality by design approach for enhanced drug delivery and cytotoxicity against cancer cells.

作者信息

Cs Jayalakshmi, Haider Mohamed, Rawas-Qalaji Mutasem, Sanpui Pallab

机构信息

Department of Biotechnology, BITS Pilani Dubai Campus, Dubai International Academic City, Dubai, UAE; Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, UAE.

Research Institute of Medical & Health Sciences, University of Sharjah, Sharjah 27272, UAE; Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, UAE.

出版信息

Colloids Surf B Biointerfaces. 2025 Jan;245:114319. doi: 10.1016/j.colsurfb.2024.114319. Epub 2024 Oct 15.

DOI:10.1016/j.colsurfb.2024.114319
PMID:39461183
Abstract

Zein, a maize protein, has been explored for constructing potential biomaterial due to its hydrophobic nature, self-assembly capability, and biocompatibility. In its nanoparticulate form, zein is a promising material for drug delivery applications, particularly in cancer treatment. Despite the importance of colloidal stability for effective drug delivery, systematic studies investigating the effect of various surface modifying agents (MAs) on the zein nanoparticles (ZNPs)-based formulations are limited. This study employs quality-by-design (QbD) approach to optimize curcumin-loaded ZNPs, enhancing colloidal stability, size, and drug-encapsulation efficiency using different MAs for potential cancer therapy. Gum arabic (GA) emerged as the optimal stabilizer, with GA-stabilized curcumin-loaded ZNPs (GA-Cur-ZNPs) achieving a particle size of 184.8 ± 2.85 nm, zeta potential of -23.4 ± 0.56 mV and 87.1 ±1.55 % drug encapsulation efficiency, along with excellent colloidal stability over two months. The optimal formulation also demonstrated sustained release of Cur over 72 h. GA-Cur-ZNPs demonstrated lower IC values and higher anti-proliferative effects on three different cancer cell lines compared to the free drug, while also exhibiting superior intracellular uptake. With negligible toxicity to human dermal fibroblast cells, the optimized Cur-GA-ZNPs show promise for safe and effective killing of cancer cells.

摘要

玉米醇溶蛋白是一种玉米蛋白,因其疏水性、自组装能力和生物相容性,已被用于构建潜在的生物材料。呈纳米颗粒形式的玉米醇溶蛋白是药物递送应用的一种有前景的材料,尤其是在癌症治疗方面。尽管胶体稳定性对有效的药物递送很重要,但研究各种表面改性剂(MAs)对基于玉米醇溶蛋白纳米颗粒(ZNPs)的制剂影响的系统研究有限。本研究采用质量源于设计(QbD)方法优化负载姜黄素的ZNPs,使用不同的MAs提高胶体稳定性、粒径和药物包封效率,用于潜在的癌症治疗。阿拉伯胶(GA)成为最佳稳定剂,GA稳定的负载姜黄素的ZNPs(GA-Cur-ZNPs)粒径为184.8±2.85 nm,zeta电位为-23.4±0.56 mV,药物包封效率为87.1±1.55 %,并且在两个月内具有出色的胶体稳定性。最佳制剂还显示姜黄素在72小时内持续释放。与游离药物相比,GA-Cur-ZNPs对三种不同癌细胞系的IC值更低,抗增殖作用更强,同时还表现出更高的细胞内摄取率。优化后的Cur-GA-ZNPs对人皮肤成纤维细胞的毒性可忽略不计,显示出安全有效地杀死癌细胞的前景。

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