phytoestrogens and Mucopolysaccharidoses

Two cationic derivatives of γ-cyclodextrin (GCD) were synthesized by functionalization with glycidyltrimethylammonium chloride (GTMAC) and ethylenediamine (EDA). Both these derivatives (GCD-GTMAC and GCD-EDA) have been shown to interact strongly with anionic biopolymers, unfractionated heparin (UFH) and mucin, the latter showing their mucoadhesive properties. They form inclusion complexes with daidzein (DAI), an isoflavone displaying a multitude of physiological effects, much more efficiently than the unmodified GCD. It was also shown that the complexes of these GCD derivatives with DAI and Nile Red penetrate human fibroblasts and murine hippocampal neuronal cells indicating that cationic GCD derivatives can be considered as potential delivery systems for isoflavones and other poorly water soluble compounds. Moreover, it was found that DAI delivered in cationic GCD complexes decreased the level of the cellular glycosaminoglycans (GAGs) in normal fibroblasts suggesting their possible application in the control of GAGs in mucopolysaccharidoses, lysosomal storage diseases caused by pathological accumulation of GAGs in the cells.

Topics: Absorption, Physiological; Animals; Cell Survival; Cells, Cultured; Drug Delivery Systems; Epoxy Compounds; Ethylenediamines; Fibroblasts; gamma-Cyclodextrins; Glycosaminoglycans; Hippocampus; Humans; Indicators and Reagents; Isoflavones; Lysosomal Storage Diseases; Mice; Mucopolysaccharidoses; Neurons; Phytoestrogens; Quaternary Ammonium Compounds; Solubility