Delivery of Antisense Oligonucleotides Using HPMA Polymer:  Synthesis of A Thiol Polymer and Its Conjugation to Water-Soluble Molecules

Abstract

Here, we report the synthesis and characterization of an HPMA-based polymer for use as a carrier for the delivery of water soluble drugs. The polymer contains active-sulfhydryl groups for coupling of ligands through a disulfide linkage. The polymer can also be prepared containing pendant amino groups in addition to the active-sulfhydryl moiety. This allows the use of different chemistries to conjugate a variety of ligands to the polymer. We demonstrate that a sulfhydryl-terminated antisense oligonucleotide can be efficiently and rapidly conjugated to the polymer. The polymer-oligonucleotide conjugate is efficiently taken up by cultured cells.