Delivery of antisense oligonucleotides using HPMA polymer: synthesis of A thiol polymer and its conjugation to water-soluble molecules.
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.
Wang
L
L
University of Utah Department of Pharmaceutics and Pharmaceutical Chemistry 421 Wakara Way, Suite 318 Salt Lake City, Utah 84108, USA. ganesan.v@duke.edu
Kristensen
J
J
Ruffner
D E
DE
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
D004220:Disulfides; D004337:Drug Carriers; D008024:Ligands; D008689:Methacrylates; D016376:Oligonucleotides, Antisense; D011108:Polymers; D013438:Sulfhydryl Compounds; C032802:hydroxypropyl methacrylate