Dual-targeted colon-based integrated micelle drug delivery system for treatment of ulcerative colitis

Abstract

Emodin (EMO) is an active ingredient of Chinese traditional medicine with the potential to reportedly treat ulcerative colitis (UC). However, the solubility of EMO in water is poor coupled with low oral bioavailability, whilst existing conventional oral preparations of the drug lack targeting ability. Thus, this work sought to design and fabricate a mannose modified colon targeted micelle drug delivery system comprising quantum dots (QDs) and EMO to obtain Eu-CS-Man-Ps-P(HEMA-DMAM)/EMO-QDs, which exhibited stable physicochemical properties, smaller average sized droplets (226.22 ± 1.83 nm), better polydispersity (PDI = 0.060 ± 0.005), negative ζ-potential (−19.19 ± 0.89 mV) and high efficiency of encapsulation (95.14 ± 0.23%). We observed Eu-CS-Man-Ps-P(HEMA-DMAM)/EMO-QDs to be an effective approach for the improvement of EMO solubility in an aqueous medium with an increased oral bioavailability (3.23 times higher than native drug) of the drug. Besides, the micelle could increase the retention and release of EMO in colonic ulcers through multi-stage targeting, improve oral bioavailability, regulate the expression of inflammatory factors and repair damaged tissues, which helped us to achieve the design goal of integrated diagnosis and treatment of UC. Conclusively, the therapeutic effect of EMO was enhanced through an integrated micelle, which exhibited good prospects in improving solubility and oral biological availability.

Keywords:

• Inflammatory bowel disease
• Emodin
• Eu-CS-Man-Ps-P(HEMA-DMAM)/EMO-QDs
• pH sensitive
• targeted therapy

Ethical approval

All experiments of animals in this study were approved by the Animal Ethics and Welfare Committee (AEWC) of Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine. The approval licence number was SCXK-2016-0006.

Acknowledgements

The authors greatly appreciate all authors for their contribution to this manuscript.

Author contributions

Zhiwei Miao and Mingjia Gu: conceptualization. Zhiwei Miao, Mingjia Gu, and Jing Yan: methodology. Zhiwei Miao, Mingjia Gu, Jing Yan, Lidan Lu, and Yan Xu: software. Zhiwei Miao, Mingjia Gu, Liqin Ning, and Yi Xu: validation. Zhiwei Miao: formal analysis. Mingjia Gu: investigation. Jing Yan and Lidan Lu: resources. Zhiwei Miao and Mingjia Gu: writing—original draft preparation. Liqin Ning and Yi Xu: writing—review and editing. Liqin Ning and Yi Xu: funding acquisition. All authors have read and agreed for the manuscript to be published.

Disclosure statement

The author reports no conflicts of interest in this work.

Data availability statement

The data presented in this study are available on request from the corresponding author.

Additional information

Funding

This work was supported by the [Funding Agency National Natural Science Foundation of China] under Grant [number 82104792]; [Funding Agency Natural Science Foundation of Nanjing University of Chinese Medicine] under Grant [number XZR2020059]; [Funding Agency Natural Science Foundation of Jiangsu Province] under Grant [number BK20181235]; [Funding Agency Natural Science Foundation of Jiangsu Province] under Grant [number BK20210134]; and [Funding Agency Suzhou science and technology project] under Grant [number SYS2020056].