Delivery of antisense oligonucleotides using HPMA polymer: synthesis of A thiol polymer and its conjugation to water-soluble molecules

Bioconjug Chem. 1998 Nov-Dec;9(6):749-57. doi: 10.1021/bc980034k.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Chromatography, Liquid
  • Disulfides / chemistry
  • Drug Carriers
  • Hydrolysis
  • Kinetics
  • Ligands
  • Methacrylates / chemistry*
  • Oligonucleotides, Antisense / chemistry*
  • Polymers / chemical synthesis*
  • Polymers / chemistry
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Sulfhydryl Compounds

Substances

  • Disulfides
  • Drug Carriers
  • Ligands
  • Methacrylates
  • Oligonucleotides, Antisense
  • Polymers
  • Sulfhydryl Compounds
  • hydroxypropyl methacrylate