期刊
EXPERT OPINION ON DRUG DELIVERY
卷 -, 期 -, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2023.2231345
关键词
biopharmaceutical properties; colon-targeted drug delivery; glutathione conjugation; self-assembled nanoliposomes; AOM; DSS-induced CAC
The researchers loaded the anti-cancer drug candidate M13 into colon-targeting ginger-derived nanoliposomes (NL) and investigated the enhanced anticancer effects of orally administered M13-NL on CAC in mouse models. M13 showed favorable physiochemical properties and no apparent immunotoxicity or mutagenic potential. The use of NL for drug delivery significantly improved the safety and efficacy of M13, and oral administration of M13-NL demonstrated excellent therapeutic effects in CAC mouse models.
ObjectiveColitis-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.MethodsThe 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.ResultsM13 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.ConclusionM13-NL is a promising oral drug formulation for CAC treatment.
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