{"title":"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。","authors":"Dingpei Long, Zahra Alghoul, Junsik Sung, Chunhua Yang, Didier Merlin","doi":"10.1080/17425247.2023.2231345","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (<i>p</i> < 0.001). Oral administration of M13-NL exhibited excellent therapeutic effects in AOM/DSS-induced CAC mice.</p><p><strong>Conclusion: </strong>M13-NL is a promising oral drug formulation for CAC treatment.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":" ","pages":"1443-1462"},"PeriodicalIF":5.0000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810011/pdf/","citationCount":"0","resultStr":"{\"title\":\"Oral administration of M13-loaded nanoliposomes is safe and effective to treat colitis-associated cancer in mice.\",\"authors\":\"Dingpei Long, Zahra Alghoul, Junsik Sung, Chunhua Yang, Didier Merlin\",\"doi\":\"10.1080/17425247.2023.2231345\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (<i>p</i> < 0.001). Oral administration of M13-NL exhibited excellent therapeutic effects in AOM/DSS-induced CAC mice.</p><p><strong>Conclusion: </strong>M13-NL is a promising oral drug formulation for CAC treatment.</p>\",\"PeriodicalId\":12229,\"journal\":{\"name\":\"Expert Opinion on Drug Delivery\",\"volume\":\" \",\"pages\":\"1443-1462\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810011/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Drug Delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17425247.2023.2231345\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/7/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425247.2023.2231345","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/7/2 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Oral administration of M13-loaded nanoliposomes is safe and effective to treat colitis-associated cancer in mice.
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.
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.
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