Phosphorus-containing star-shaped polymer conjugates for biomedical applications

Abstract

A novel phosphorus-containing biocompatible and biodegradable star-shaped polymer was designed as a precursor polymer for obtaining sugar or drug conjugates. The star polymer bearing three arms was synthesized applying the “coupling on” approach. Linear oligo(oxyethylene H-phosphonate) with a terminal hydroxyl group was prepared and used as functional arms able to react with tris(2,3-epoxypropyl) isocyanurate as core in the presence of boron trifluoride etherate as catalyst. The H-phosphonate moieties in the arm chains were transformed into trimethylsilyl phosphite groups and further via Staudinger reaction they were converted into phosphoramidates bearing specific residues. When the Staudinger reaction was carried out with a glucose-containing azide, i.e. 2-p-azidobenzamide-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-alpha-D-glucopyranose, the product was a star-shaped glycopolymer. The conjugation of AZT yielded a star-shaped polymer-drug conjugate. Multinuclear NMR spectroscopy was applied as a powerful tool for determination of the conversion and structure of the reaction products. Analytical ultracentrifugation, dynamic and electrophoretic light scattering techniques were used for characterization of the star polymers and conjugates, as well as in binding studies with Concanavalin A. Drug release measurements and cytotoxicity tests were also performed. The obtained results evidenced feasible synthetic procedures for preparation of biocompatible phosphorus containing star-shaped glycopolymer and drug conjugate.