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Abstract
To take advantage of the cytoadhesive characteristics of Wheat germ agglutinin (WGA) for improved particulate drug delivery, the interaction between WGA-grafted poly(D,L-lactic-co-glycolic acid)-microspheres and Caco-2 monolayers was investigated using bovine serum albumin (BSA) or glycine coated microspheres as a control. Covalent immobilization of WGA by the carbodiimide/N-hydroxysuccinimide-method on 4 μm microspheres yielded a surface density of 9.67 ± 1.21 × 106 molecules/particle, whereas 0.22 ± 0.04 × 106 WGA-molecules were bound by physical adsorption. After storage for 21 days in HEPES-buffer and treatment of the particles with 5 M urea, 86% of covalently linked lectin was still attached to the particles. At 4°C the Caco-2 binding rate of both, WGA- and BSA-modified particles increased with addition of increasing numbers of particles until saturation was reached at 38150 ± 1740 (WGA) or 12066 ± 1195 (BSA) microspheres bound/mm2 Caco-2 monolayer. Inhibition of Caco-2 binding of WGA-functionalized microspheres by chitotriose indicated for specificity of the interaction. As observed by confocal laser scanning microscopy, the fluorescein-loading of the particles was accumulated intracellularly after incubation of Caco-2 monolayers with WGA-modified microspheres contrary to glycine-grafted microspheres. Additionally, in case of WGA-functionalized microspheres the amount of cell associated fluorescein was 200-fold higher than that of the free solution.
In conclusion, WGA-modified microspheres are expected to enhance intestinal transport of incorporated drugs due to cytoadhesion provided by the lectin coating.