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Description
(2-Hydroxypropyl)-β-cyclodextrin is a widely used drug delivery vehicle to improve the stability and bioavailability.
In Vitro
Cell treatment with (2-Hydroxypropyl)-β-cyclodextrin results in the activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and in enhancement of the cellular autophagic clearance capacity[1]. (2-Hydroxypropyl)-β-cyclodextrin treatment reduces intracellular cholesterol resulting in significant leukemic cell growth inhibition through G2/M cell-cycle arrest and apoptosis. The IC50 values for (2-Hydroxypropyl)-β-cyclodextrin after 72 hours exposure are in the range of 3.86–10.09 mM. (2-Hydroxypropyl)-β-cyclodextrin also shows anticancer effects against CML cells expressing a T315I BCR-ABL mutation (that confers resistance to most ABL tyrosine kinase inhibitors), and hypoxia-adapted CML cells that have characteristics of leukemic stem cells. In addition, colony forming ability of human primary AML and CML cells is inhibited by (2-Hydroxypropyl)-β-cyclodextrin.
In Vivo
(2-Hydroxypropyl)-β-cyclodextrin administration promotes transcription factor EB-mediated clearance of proteolipid aggregates that accumulate due to inefficient activity of the lysosome-autophagy system in cells derived from a patient with a lysosomal storage disorder. Intraperitoneal injection of (2-Hydroxypropyl)-β-cyclodextrin significantly improves survival in leukemia mouse models. Systemic administration of (2-Hydroxypropyl)-β-cyclodextrin to mice has no significant adverse effects.