title: Wheat germ agglutinin-functionalised crosslinked polyelectrolyte microparticles for local colon delivery of 5-FU: in vitro efficacy and in vivo gastrointestinal distribution.
abstract: We have previously reported the development and characterisation of wheat germ agglutinin (WGA)-functionalised chitosan-Ca-alginate (CTS-Ca-ALG) microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU). In the present work, our goal was to evaluate the potential of these carriers for efficient treatment of colon cancer by studying in vitro permeability and cell association of 5-FU and [methyl-³H]thymidine uptake in Caco-2 cells, as well as in vivo gastrointestinal distribution. The amount of 5-FU permeated through Caco-2 cells was 15.1, 7.7 and 6.5% for 5-FU solution, CTS-Ca-ALG MPs and WGA conjugates. The concentration of 5-FU associated with Caco-2 cells was significantly greater when delivered from MPs. By incorporation of 5-FU into MPs and further decoration with WGA, an increased [methyl-³H]thymidine uptake was observed few hours after continuous drug treatment followed by significantly reduced uptake after 6 h. Gastrointestinal distribution was in favour of increased localisation and concentration of the particles in colon region.
authors.affiliation: Institute of Pharmaceutical Technology, Faculty of Pharmacy, University "Ss Cyril and Methodius" , Vodnjanska 17, P.O. Box 36, 1000 Skopje , Macedonia.
authors.forename: Marija
authors.initials: M
authors.lastname: Glavas-Dodov
authors.forename: Bente
authors.initials: B
authors.lastname: Steffansen
authors.forename: Maja S
authors.initials: MS
authors.lastname: Crcarevska
authors.forename: Nikola
authors.initials: N
authors.lastname: Geskovski
authors.forename: Simona
authors.initials: S
authors.lastname: Dimchevska
authors.forename: Sonja
authors.initials: S
authors.lastname: Kuzmanovska
authors.forename: Katerina
authors.initials: K
authors.lastname: Goracinova
mesh_terms: D000464:Alginates / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D048271:Chitosan / Q000031:analogs & derivatives / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014908:Triticum / Q000737:chemistry; D014909:Wheat Germ Agglutinins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000464:Alginates; D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D006603:Hexuronic Acids; D014909:Wheat Germ Agglutinins; D020723:Glucuronic Acid; D048271:Chitosan; D005472:Fluorouracil