Macromolecular prodrugs V. Polymer-broxuridine conjugates

Broxuridine (BrdU) was covalently bound to α,β-poly[(2-hydroxyethyl)-dl-aspartamide](PHEA) and α,β-poly[(2-aminoethyl)-DL-aspartamide]-α,β-poly[(2-hydroxyethyl)-DL-aspartamide](PAHA). BrdU was first chemically modified to 3′-O-acetyl-5′-O-chloroformyl-5-bromo-2′-deoxyuridine (AcCBrdU) and 3′-O-acetyl-5′-O-phosphooxydichloride-5-bromo-2′-deoxyuridine (AcPBrdU). These compounds were bound to PHEA by carbonate and phosphodiester linkages, respectively. 5-Bromo-2′-deoxyuridine 5′-monophosphate (PBrdU) was linked to PAHA by an amide type bond. Neuroepithelial cells were used as a model system to assess the suitability of the conjugated BrdU for cell proliferation. Parallel experiments were performed with unconjugated BrdU and the extent of incorporation into DNA was determined by immunocytochemistry using an BrdU antibody. The results from these studies suggest that conjugated BrdU can be used as an alternative to currently used means of BrdU delivery.