Lectin-decorated nanoparticles enhance binding to the inflamed tissue in experimental colitis

A major limitation in the drug treatment of inflammatory bowel disease is the inability to deliver the drug selectively towards the inflamed tissues. Nanotechnology-based drug delivery systems have led to an amelioration of the therapeutic selectivity but still the majority of the entrapped drug is eliminated without exercising a therapeutic effect. Here, lectin-decorated drug loaded nanoparticles (NP) are suggested for active targeting and selective adhesion to the inflamed tissue in experimental colitis. Peanut (PNA) and wheat germ (WGA) lectins were covalently bound to the surface of NP and were tested for their stability and degree of bioadhesion in cell culture. In-vivo, the selectivity of bioadhesion and distribution of NP throughout the intestinal tract as well as the therapeutic benefit for glucocorticoid loaded lectin-NP was studied in murine colitis models. Quantitative adhesion analyses showed that lectin-conjugated NP exhibited a much higher binding and selectivity to inflamed tissue compared to plain NP (PNA conjugates: 52.2±5.6%; WGA conjugates: 22.0±0.8%; plain NP: 18.6±9.8%). Lectin-associated NP revealed a further increase in the selectivity of bioadhesion towards inflamed tissues which partially translates into increased therapeutic efficiency. In terms of therapeutic efficiency, all glucocorticoid containing formulations revealed an enhanced therapeutic effect with lectin conjugates especially PNA-NP (myeloperoxidase: 55±37U/g; TNF-alpha: 3880±380U/g) compared to plain NP (myeloperoxidase: 145±98U/g; TNF-alpha: 6971±1157U/g). Targeted NP by using lectins, especially with PNA, as stable targeting moiety in the gastrointestinal tract appears to be a very promising tool in future treatment of inflammatory bowel disease.