DELIVERY OF ANTISENSE OLIGONUCLEOTIDES USING HPMA POLYMER - SYNTHESISOF A THIOL POLYMER AND ITS CONJUGATION TO WATER-SOLUBLE MOLECULES

Here, we report the synthesis and characterization of an HPMA-based po lymer for use as a carrier for the delivery of water soluble drugs. Th e polymer contains active-sulfhydryl groups for coupling of ligands th rough a disulfide linkage. The polymer can also be prepared containing pendant amino groups in addition to the active-sulfhydryl moiety. Thi s allows the use of different chemistries to conjugate a variety of li gands to the polymer. We demonstrate that a sulfhydryl-terminated anti sense oligonucleotide can be efficiently and rapidly conjugated to the polymer. The polymer-oligonucleotide conjugate is efficiently taken u p by cultured cells.