Electrochemical method for entrapment of oligonucleotides in polymer-coated electrodes.
Oligonucleotides were incorporated into conducting films of poly(3, 4-ethylene dioxythiophene) by an electrochemical method that involves two steps. The electrode is first coated with the polymer film by electropolymerization followed by electrooxidation of the formed polymer in the presence of the oligonucleotide. Neutral water soluble polymers such as poly(vinylpyrrolidone) or poly(ethylene glycol) were added to the polymerizing medium resulting in higher incorporation yields of oligonucleotides. The results showed that a payload of about 1.5 nmol/cm2 can be achieved in an 8 micron thick film for an oligomer concentration of about 70 microM in the working solution. Various physical methods were used to analyze the surface of the polymer-coated electrodes. Results showed the presence of domains of varying sizes at the film surface, corresponding to the insertion of the hydrophilic polymer within the matrix of the conductive polymer. The release of entrapped oligonucleotides from the coated film exhibited a three-step profile: a "burst" period during the first 5 min followed by an intermediate and a very slow release period lasting several days. Such polymer films could be exploited as useful reservoirs of biologically active substances for in vivo delivery to targeted tissues. For example, coated stents that can release antiproliferative agents such as antisense oligonucleotides at the site of balloon dilatation may be of interest in the treatment of postangioplasty restenosis.
ITODYS, Université Paris VII, 1 Rue Guy de la Brosse, 75005 Paris, France.
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D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D004563:Electrochemistry; D004566:Electrodes; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000302:isolation & purification*; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016376:Oligonucleotides, Antisense; D011108:Polymers; C121383:poly(3,4-ethylene dioxythiophene)