title: Folic acid-PEO-labeled liposomes to improve gastrointestinal absorption of encapsulated agents.
abstract: The design of targeted oral liposomes is anticipated to improve the systemic delivery of poorly absorbed agents, such as proteins and peptides. A poly(ethylene oxide) (PEO)-folic acid (FA) derivative was prepared and evaluated for improving liposome transport across a model gastrointestinal cell line (Caco-2). FA-PEO-cholesterol (Chol) derivatives were synthesized and adsorbed at liposome surfaces encapsulating Texas Red((R))-Dextran 3000 (TR-dex), a poorly-absorbed, neutral, hydrophilic, large molecular weight (M(w)) marker. Apparent permeabilities (P(app)) of Caco-2 cells to FA-PEO conjugates, TR-dex, uncoated TR-dex liposomes, and FA-coated TR-dex liposomes were compared at 2 h post-administration. Intracellular delivery of TR-dex was detected by fluorescence microscopy. An increase in intracellular accumulation of TR-dex associated with FA-PEO-coated liposomes, but not other formulations, was evidence of the potential of FA-targeted liposomes in the oral delivery of poorly absorbed, large M(w) agents.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: K E
authors.initials: KE
authors.lastname: Anderson
authors.forename: B R
authors.initials: BR
authors.lastname: Stevenson
authors.forename: J A
authors.initials: JA
authors.lastname: Rogers
mesh_terms: D000042:Absorption / Q000187:drug effects; D018938:Caco-2 Cells / Q000378:metabolism; D002214:Capsules / Q000493:pharmacokinetics*; D003911:Dextrans / Q000493:pharmacokinetics; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism*; D005079:Excipients / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D005492:Folic Acid / Q000493:pharmacokinetics*; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics*; D010952:Plasma Substitutes / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D014966:Xanthenes / Q000493:pharmacokinetics
chemical_list: D002214:Capsules; D003911:Dextrans; D005079:Excipients; D008081:Liposomes; D010952:Plasma Substitutes; D014966:Xanthenes; D011092:Polyethylene Glycols; C034657:Texas red; D005492:Folic Acid