Solubilization of cyclosporin A in dextran-g-polyethyleneglycolalkyl ether polymeric micelles.
Solubilization of the poorly water-soluble drug, Cyclosporin A (CsA), in aqueous dispersions of dextran-grafted-polyethyleneglycolalkyl ether (DEX-g-PEG-Cn) polymeric micelles was examined as a function of copolymer structure. In aqueous solution, DEX-g-PEG-Cn form polymeric micelles of low critical association concentrations (CAC) and small micelle sizes as determined by fluorescence spectroscopy and dynamic light scattering (DLS). Copolymers with longer polysaccharide chain showed larger CAC and mean diameter. The percentage of CsA loading into micelles was determined by high performance liquid chromatography. It was significantly larger in polymeric micelles compared to unmodified dextrans. It increased with increasing number of PEG-Cn units grafted per dextran chain and decreasing dextran molecular weight. The cytotoxicity of DEX-g-PEG-C(16) polymeric micelles towards Caco-2 cells, tested by MTT cytotoxicity assay, was significantly lower than that of free PEG-C(16) molecules. It can be concluded that the length of the hydrophilic part as well as the content and chemical nature of the hydrophobic substituents have an important effect on the ability of polymeric micelles to solubilize poorly-water soluble drugs.
Francis
Mira F
MF
Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada.
Lavoie
Luc
L
Winnik
Françoise M
FM
Leroux
Jean Christophe
JC
D018938:Caco-2 Cells; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry*; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008823:Micelles; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility
D003911:Dextrans; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D011092:Polyethylene Glycols; D016572:Cyclosporine