Saccharide complexes improve binding of Pentosanpolysulfate and Heparin to bladder epithelium

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Apr 17 2006

Anionic glycosaminoglycans including pentosanpolysulphate (PPS) and heparin show weak or no staining of the bladder epithelium and thus do not bind to human or rabbit bladder epithelium in any appreciable amounts.

Muthusamy and colleagues attached galactosyl residues to PPS and heparin in an effort to encourage binding to the endogenous lectins in the bladder and thus possibly improve efficacy of glycosaminoglycan (GAG) therapy.

The mode of action of the exogenous glycosaminoglycans is unclear, but is presumed to be the coating of the bladder surface, thereby replacing the missing or nonfunctional GAG found in the normal bladder epithelium. Possible reasons for their limited efficacy include low bioavailability (with oral administration) and absent or minimal binding to the bladder (with oral or intravesical administration). In their study, the highly anionic polysaccharides such as hyaluronan, pps, and heparin do not bind to bladder surfaces, and in the in vitro study only 2-4% of these polysaccharides associated even temporarily with the rabbit epithelium, and the major portion was removed by rinsing.

They report that the binding of heparin and PPS to human and rabbit bladder increased significantly by covalently attaching lactose to the molecules. PPS and heparin modified by attachment of lactose, as well as the asialo mucin glycoproteins, bound strongly to human and rabbit bladders. This binding is mediated by the interaction of the endogenous bladder galactins and the non-reducing galactose terminals in the lactose attached to the anionic polysaccharides or the asialoglyoproteins. They surmise that it is possible that lactose-modified PPS or heparin might be more effective in the treatment of painful bladder syndrome.

This is a very interesting contribution to the literature, as it demonstrates a possible reason why oral PPS and intravesical heparin treatment of painful bladder syndrome has proven so frustrating for patients and clinicians, and how modification of the molecules might improve treatment results if the if the underlying etiologic theory on which the treatment is based is actually valid.

By Philip Hanno, MD

Reference: Urology 67:209-213, 2006 (January)