title: 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.
authors.affiliation: University of Utah Department of Pharmaceutics and Pharmaceutical Chemistry 421 Wakara Way, Suite 318 Salt Lake City, Utah 84108, USA. ganesan.v@duke.edu
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Kristensen
authors.forename: D E
authors.initials: DE
authors.lastname: Ruffner
mesh_terms: D002478:Cells, Cultured; D002853:Chromatography, Liquid; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers; D006868:Hydrolysis; D007700:Kinetics; D008024:Ligands; D008689:Methacrylates / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013438:Sulfhydryl Compounds
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D008024:Ligands; D008689:Methacrylates; D016376:Oligonucleotides, Antisense; D011108:Polymers; D013438:Sulfhydryl Compounds; C032802:hydroxypropyl methacrylate