Breaking barriers: targeted delivery of resveratrol in lung cancer using folate-integrated and pH-responsive hybrid nanocarriers

IF 3 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2025-07-29 DOI:10.1186/s43094-025-00850-2

Sanjoy Das, Malay K. Das, Taison Jamatia, Nayan Ranjan Ghose Bishwas, Dhritiman Roy, Emdormi Rymbai

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引用次数: 0

Abstract

Background

Targeting lung cancer while sparing healthy cells is the cornerstone of chemotherapy; however, bioavailability issues and complex biological barriers prevent their accumulation in the tumor sites. Working on this rationale, the present study was aimed to develop novel and affordable hybrid nanocarriers combined with folate and pH-responsive functionalities for targeted delivery of Resveratrol (FOL-RSV-LPHNCs).

Methods

The developed FOL-RSV-LPHNCs were first optimized by the design of experiment with Box–Behnken design and then characterized for physicochemical properties, cytotoxicity, in vivo pharmacokinetic behavior and anticancer efficacy in the xenograft mouse model.

Results

Results showed that optimized FOL-RSV-LPHNCs had a monodisperse spherical size of 247.86 ± 0.30 nm, entrapment efficiency of 93.72 ± 0.10% and drug loading of 4.16 ± 0.02%, respectively. The amount of RSV released from FOL-RSV-LPHNCs was 96.53 ± 2.16% at pH 5.8 and 23.21 ± 2.01% at pH 7.4, indicative of a pH-responsive release pattern and good physiological stability. In vitro cytotoxicity study revealed that FOL-RSV-LPHNCs remarkably inhibited the viability of A549 cells and produced negligible toxic effect on Wi-38 healthy cells. The single-dose intravenous administration of FOL-RSV-LPHNCs displayed 3.79-fold longer AUC_0-∞, 3.54-fold greater t_1/2 and 4.16-fold higher MRT_0-∞ than free RSV. Finally, in vivo targeting and anticancer studies demonstrated that FOL-RSV-LPHNCs selectively internalized to the cancerous region and suppressed the tumor volume with an 8.66-fold higher rate in the xenograft mouse model. The folate receptor-mediated uptake mainly facilitates this superior therapeutic response which was further confirmed by in silico molecular docking and dynamic simulation.

Conclusions

Our findings suggested that FOL-RSV-LPHNCs might serve as an auspicious nanoplatform for targeted drug delivery and treatment of lung cancer.

Graphical Abstract

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突破障碍：使用叶酸整合和ph响应的混合纳米载体靶向递送肺癌白藜芦醇

背景：在保留健康细胞的同时靶向肺癌是化疗的基石；然而，生物利用度问题和复杂的生物屏障阻止了它们在肿瘤部位的积累。基于这一基本原理，本研究旨在开发新型且价格合理的混合纳米载体，结合叶酸和ph响应功能，用于靶向递送白藜芦醇（foll - rsv - lphncs）。方法采用Box-Behnken实验设计对制备的foll - rsv - lphnc进行优化，并对其在异种移植小鼠模型中的理化性质、细胞毒性、体内药动学行为和抗癌效果进行表征。结果优化后的foll - rsv - lphncs单分散球形粒径为247.86±0.30 nm，包封效率为93.72±0.10%，载药量为4.16±0.02%。在pH值为5.8时，foll -RSV- lphncs的RSV释放量为96.53±2.16%，在pH值为7.4时，RSV释放量为23.21±2.01%，具有pH响应型释放模式和良好的生理稳定性。体外细胞毒性研究表明，foll - rsv - lphncs显著抑制A549细胞的活力，对Wi-38健康细胞的毒性作用可忽略不计。与游离RSV相比，单剂量静脉给药foll -RSV- lphncs的AUC0-∞长3.79倍，t1/2长3.54倍，MRT0-∞高4.16倍。最后，体内靶向和抗癌研究表明，在异种移植小鼠模型中，foll - rsv - lphncs选择性内化到癌区，并以8.66倍的高速率抑制肿瘤体积。叶酸受体介导的摄取主要促进了这种优越的治疗反应，这一点在硅分子对接和动态模拟中得到了进一步证实。结论foll - rsv - lphncs可作为靶向给药和治疗肺癌的纳米平台。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

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

自引率

0.00%

发文量

审稿时长

23 weeks

期刊介绍： Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.