This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Lou, X. Articles by Chirila, T. V. Search for Related Content PubMed PubMed Citation Articles by Lou, X. Articles by Chirila, T. V. Social Bookmarking                         What's this?

Synthetic Hydrogels as Carriers in Antisense Therapy: Preliminary Evaluation of an Oligodeoxynucleotide Covalent Conjugate with a Copolymer of 1-Vinyl-2-Pyrrolidinone and 2-Hydroxyethyl Methacrylate

Kerryn L. Garrett

Piroska E. Rakoczy

Traian V. Chirila

Lions Eye Institute, Department of Biomaterials & Polymer Research, and Department of Molecular Ophthalmology and Centre for Ophthalmology & Visual Science, University of Western Australia, 2 Verdun Street, Nedlands, Western Australia 6009, Australia

A major challenge of the antisense therapeutic strategies is the development of improved systems for the delivery of antisense oligodeoxynucleotides (AS ODNs) in order to enhance the cellular uptake, to assure a better efficiency in reaching the target tissue, and to provide sustained delivery over longer periods of time. Because the current methods for delivery (liposomes and cationic polymers) present somedisadvantages, the attention was directed toward the use of neutral polymers as carriers for the AS ODNs. Based on our previous work on synthetic hydrogels for vitreous substitution, we developed a poly[1-vinyl-2-pyrrolidinone-co-(2-hydroxyethyl methacrylate)] hydrogelas a potential carrier for AS ODNs. We have previously demonstrated that such hydrogels are not cytotoxic, and they may have growth-promoting effects on cultured fibroblasts. This copolymer also has the advantage of being injectable. In this study, a specific AS ODN was synthesized and then covalently bound to the copolymer via carbodiimide coupling method. The resulting conjugate was subjected to in vitro release experiments over 46 days in the presence of bovine vitreous humor. Compared with the control (no enzyme present), a significantamount of covalently bound ODN was released from the ODN-hydrogel conjugate, suggesting the possibility of using such systems for the sustained delivery of AS ODNs.

Key Words: antisense therapy • oligodeoxynucleotides • VP-HEMA copolymers • hydrogels • vitreous humor • sustained release

Journal of Biomaterials Applications, Vol. 15, No. 4, 307-320 (2001)
DOI: 10.1106/LVPH-0P1F-V947-RWD1


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?