Cyclodextrin Complexes: A New Hope Against Atherosclerosis

Recently, increasing evidence shows that cyclodextrins have an inhibitory effect against atherosclerosis, a chronic disease inducing atherosclerotic cardiovascular diseases (ASCVDs). The authors hypothesized that drug-cyclodextrin inclusion complexes probably also have anti-atherosclerotic effects because free cyclodextrins will exist for a period of time in vivo after the release of drugs from drug-cyclodextrin inclusion complexes. To test this hypothesis, hydroxypropyl-β-cyclodextrin (HPβCD) encapsulating cholesterol or lipids was utilized to mimic drug-cyclodextrin inclusion complexe and the anti-atherosclerotic efficacy of the cholesterol-/lipids-HPβCD inclusion complexes was evaluated in an atherosclerotic animal model (high-fat-fed ApoE^-/- mice) by analyzing blood lipid profiles and atherosclerotic lesions in the entire aorta, the aortic arch, and the aortic root. The results reveal that both cholesterol- and lipids-HPβCD inclusion complexes significantly reversed blood lipid increase and plaque formation, implying that similar to free cyclodextrins drug-cyclodextrin inclusion complexes potentially also have anti-atherosclerotic efficacy. The data provide strong evidence for the notion and guideline that drug-cyclodextrin inclusion complexes are potentially a dual-use drug and the possibility of using drug-cyclodextrin inclusion complexes instead of free cyclodextrins for the treatment of atherosclerosis or ASCVDs. It also implies that the anti-atherosclerotic efficacy of the cyclodextrin part should be considered/excluded while evaluating the anti-atherosclerotic efficacy of a specific drug in its cyclodextrin inclusion complexes.

Yuanfang Li, Yuan Zhang, Mengyi Lan, Zhilu Fan, Tingting Gong, Langtao Xu, Tong Rong, Kun Wang, Huaying Wang, Meiying Ao, Yong Chen (2025) Anti-atherosclerotic effect of lipid/cholesterol-cyclodextrin inclusion complexes similar to free cyclodextrins in ApoE-/- mice fed a high-fat diet. Carbohydrate Polymer Technologies and Applications 10, 100811. https://doi.org/10.1016/j.carpta.2025.100811