title: Enhanced delivery of daidzein into fibroblasts and neuronal cells with cationic derivatives of gamma-cyclodextrin for the control of cellular glycosaminoglycans.
abstract: 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.
authors: Faculty of Chemistry, Jagiellonian University, Kraków, Poland.
authors: Kamil
authors: K
authors: Kamiński
authors: Faculty of Chemistry, Jagiellonian University, Kraków, Poland.
authors: Monika
authors: M
authors: Kujdowicz
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
authors: Małgorzata
authors: M
authors: Kajta
authors: Faculty of Chemistry, Jagiellonian University, Kraków, Poland.
authors: Maria
authors: M
authors: Nowakowska
authors: Faculty of Chemistry, Jagiellonian University, Kraków, Poland. Electronic address: szczubia@chemia.uj.edu.pl.
authors: Krzysztof
authors: K
authors: Szczubiałka
mesh_terms: D065567:Absorption, Physiological; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000009:adverse effects; D004852:Epoxy Compounds / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D007529:Isoflavones / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D016464:Lysosomal Storage Diseases / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009083:Mucopolysaccharidoses / Q000188:drug therapy / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D048789:Phytoestrogens / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D012995:Solubility; D047408:gamma-Cyclodextrins / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D004852:Epoxy Compounds; D005029:Ethylenediamines; D006025:Glycosaminoglycans; D007202:Indicators and Reagents; D007529:Isoflavones; D048789:Phytoestrogens; D000644:Quaternary Ammonium Compounds; D047408:gamma-Cyclodextrins; C045006:glycidyl trimethylammonium; C031234:ethylenediamine; C004742:daidzein
keywords: Daidzein; Fibroblasts; Glycosaminoglycans; Hippocampal neuronal cells; Mucopolysaccharidosis; γ-cyclodextrin