Oral administration of M13-loaded nanoliposomes is safe and effective to treat colitis-associated cancer in mice.

IF 5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert Opinion on Drug Delivery Pub Date : 2023-07-01 Epub Date: 2023-07-02 DOI:10.1080/17425247.2023.2231345

Dingpei Long, Zahra Alghoul, Junsik Sung, Chunhua Yang, Didier Merlin

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引用次数: 0

Abstract

Objective: Colitis-associated cancer (CAC) treatment lacks effective small-molecule drugs and efficient targeted delivery systems. Here, we loaded M13 (an anti-cancer drug candidate) to colon-targeting ginger-derived nanoliposomes (NL) and investigated if orally administered M13-NL could enhance the anticancer effects of M13 in CAC mouse models.

Methods: The biopharmaceutical properties of M13 were assessed by physicochemical characterizations. The in vitro immunotoxicity of M13 was assessed against PBMCs using FACS and the mutagenic potential of M13 was evaluated by the Ames assay. The in vitro efficacy of M13 was tested in 2D- and 3D-cultured cancerous intestinal cells. AOM/DSS-induced CAC mice were used to evaluate the therapeutic effects of free M13 or M13-NL on CAC in vivo.

Results: M13 has beneficial physiochemical properties, including high stability, and no apparent immunotoxicity or mutagenic potential in vitro. M13 is effective against the growth of 2D- and 3D-cultured cancerous intestinal cells in vitro. The in vivo safety and efficacy of M13 were significantly improved by using NL for drug delivery (p < 0.001). Oral administration of M13-NL exhibited excellent therapeutic effects in AOM/DSS-induced CAC mice.

Conclusion: M13-NL is a promising oral drug formulation for CAC treatment.

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口服M13负载纳米脂质体治疗小鼠结肠炎相关癌症是安全有效的。

目的：大肠杆菌相关性癌症（CAC）治疗缺乏有效的小分子药物和有效的靶向递送系统。在此，我们将M13（抗癌候选药物）装载到结肠靶向的姜源纳米脂质体（NL）中，并研究口服M13-NL是否可以增强M13在CAC小鼠模型中的抗癌作用。方法：采用理化性质对M13的生物制药性能进行评价。使用FACS评估M13对PBMC的体外免疫毒性，并通过Ames测定评估M13的诱变潜力。在2D和3D培养的癌性肠细胞中测试了M13的体外功效。使用AOM/DSS诱导的CAC小鼠在体内评估游离M13或M13-NL对CAC的治疗效果。结果：M13具有良好的理化性质，包括高稳定性，在体外没有明显的免疫毒性或诱变潜力。M13对体外2D和3D培养的癌性肠细胞的生长有效。通过使用NL进行药物递送，M13的体内安全性和有效性显著提高（p 结论：M13-NL是一种很有前景的CAC口服药物。

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

Expert Opinion on Drug Delivery 医学-药学

CiteScore

11.10

自引率

3.00%

发文量

104

审稿时长

3 months

期刊介绍： Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.