Folic acid-PEO-labeled liposomes to improve gastrointestinal absorption of encapsulated agents

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. (C) 1999 Elsevier Science B.V. All rights reserved.