title: Exploiting the vitamin B12 pathway to enhance oral drug delivery via polymeric micelles.
abstract: Vitamin B12 (VB12)-modified dextran-g-polyethyleneoxide cetyl ether (DEX-g-PEO-C16) was synthesized by linking VB12 residues to a DEX-g-PEO-C16 copolymer via a 2,2'-(ethylenedioxy)bis(ethylamine) spacer. The level of VB12 substitution on the DEX-g-PEO-C16 copolymer reached 1.68% (w/w). In aqueous solution, DEX-based copolymers form micelles that can entrap within their hydrophobic core up to 8.5% w/w of cyclosporin A (CsA), a poorly water soluble immunosuppressant. The permeability of Caco-2 cell membranes to CsA incorporated in VB12 modified and unmodified polymeric micelles was monitored in the presence and absence of intrinsic factor (IF). The apical (AP) to basolateral (BL) permeation of CsA through Caco-2 cell monolayers after 24 h of transport was significantly higher (1.8 and 2.3 times in absence and presence of IF, respectively) in the case of CsA loaded in VB12-modified polymeric micelles, compared to CsA in unmodified micelles. The results point to possible improvement in the application of polysaccharide-based polymeric micelles as targeted polymeric drug carriers for the oral delivery of poorly water soluble drugs.
authors.affiliation: Faculty of Pharmacy and Department of Chemistry, University of Montreal, C.P. 6128 Succ. Centre-ville, Montreal, Quebec H3C 3J7, Canada.
authors.forename: Mira F
authors.initials: MF
authors.lastname: Francis
authors.forename: Mariana
authors.initials: M
authors.lastname: Cristea
authors.forename: Françoise M
authors.initials: FM
authors.lastname: Winnik
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D016572:Cyclosporine / Q000737:chemistry / Q000494:pharmacology*; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000166:cytology; D004987:Ethers / Q000737:chemistry; D005936:Glucans / Q000737:chemistry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007422:Intestines / Q000166:cytology; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008954:Models, Biological; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry; D012995:Solubility; D013997:Time Factors; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000737:chemistry*; D014867:Water
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D004987:Ethers; D005936:Glucans; D007166:Immunosuppressive Agents; D008823:Micelles; D011108:Polymers; D011134:Polysaccharides; C506475:vitamin B12-modified dextran-g-polyethylene oxide cetyl ether; D014867:Water; D016572:Cyclosporine; D014805:Vitamin B 12