title: Controlled delivery of antisense oligodeoxynucleotide from cationically modified phosphorylcholine polymer films.
abstract: Antisense strategy is a promising approach for the prevention of in-stent restenosis if therapeutic agents such as antisense oligodeoxynucleotides (AS-ODNs) can be successfully delivered to the implant site. Optimizing the routes and conditions for controlled loading and release of therapeutic agents from a biocompatible polymer coating is still required. In this study, phosphorylcholine (PC) polymer films bearing different cationic charge densities were deposited onto smooth silicon substrates. The thickness of these films was determined by spectroscopic ellipsometry (SE). Human c-myc AS-ODNs were incorporated into the PC polymer films by immersion in concentrated AS-ODN solution and eluted into PBS under physiological conditions. The elution profile was monitored by UV spectrometry and gel electrophoresis. Cellular uptake of the eluted AS-ODN into vascular smooth muscle cells (VSMCs) was evaluated by fluorescence microscopy. The results showed that ODN loading capacities increased with film thickness and were also strongly dependent on the cationic charge density. AS-ODN release was characterized by a slight initial burst in the first half hour followed by a period of sustained release up to 8 days. Gel electrophoresis demonstrated DNA integrity, and different transfection efficiencies were observed when the eluted ODNs were transfected into VSMCs. These results demonstrated that cationically modified PC polymers are capable of delivery of antisense ODNs in a controlled manner and that they are well suited for specific biomedical devices such as DNA-eluting stents.
authors.affiliation: Biological Physics Group, School of Physics and Astronomy, The University of Manchester, Sackville Street Building, Sackville Street, Manchester M60 1QD, UK.
authors.forename: ZhuoQi
authors.initials: Z
authors.lastname: Zhang
authors.forename: XiChuan
authors.initials: X
authors.lastname: Cao
authors.forename: XiuBo
authors.initials: X
authors.lastname: Zhao
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Withers
authors.forename: Cathy M
authors.initials: CM
authors.lastname: Holt
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.forename: Jian R
authors.initials: JR
authors.lastname: Lu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry; D055592:Biophysical Phenomena; D001703:Biophysics; D006801:Humans; D008856:Microscopy, Fluorescence; D008968:Molecular Conformation; D009130:Muscle, Smooth / Q000166:cytology; D009841:Oligonucleotides / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry*; D010767:Phosphorylcholine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D013552:Swine
chemical_list: D001672:Biocompatible Materials; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011108:Polymers; D016271:Proto-Oncogene Proteins c-myc; D010767:Phosphorylcholine