Ultrapure chitosan oligomers as carriers for corneal gene transfer.
| Title: | Ultrapure chitosan oligomers as carriers for corneal gene transfer. |
|---|---|
| Authors: | Klausner EA; Department of Pharmaceutical Sciences, Midwestern University Chicago College of Pharmacy, Downers Grove, IL 60515, USA. eklausner@midwestern.edu; Zhang Z; Chapman RL; Multack RF; Volin MV |
| Source: | Biomaterials [Biomaterials] 2010 Mar; Vol. 31 (7), pp. 1814-20. Date of Electronic Publication: 2009 Oct 30. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8100316 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5905 (Electronic) Linking ISSN: 01429612 NLM ISO Abbreviation: Biomaterials Subsets: MEDLINE |
| Imprint Name(s): | Publication: : Amsterdam : Elsevier Science; Original Publication: [Guilford, England] : IPC Science and Technology Press, 1980- |
| MeSH Terms: | Gene Transfer Techniques*; Chitosan/*chemistry ; Cornea/*metabolism ; Drug Carriers/*chemistry; DNA/chemistry ; Green Fluorescent Proteins/metabolism ; Luciferases/genetics ; Luciferases/metabolism ; Nanoparticles/chemistry ; Animals ; COS Cells ; Cells, Cultured ; Chlorocebus aethiops ; Electrophoretic Mobility Shift Assay ; Gene Expression Regulation ; Microscopy, Fluorescence ; Particle Size ; Rats ; Transfection |
| Abstract: | NOVAFECT chitosans are ultrapure chitosan oligomers that were recently marketed as carriers for non-viral gene therapy. There are no reports on systematic design and improvement of formulations based on NOVAFECT chitosans for gene delivery. Therefore, we have designed and characterized chitosan-DNA nanoparticles based on NOVAFECT. We found that the size of oligomeric chitosan-DNA nanoparticles is small, or=44.1+/-3.5 millivolt. In vitro transfection studies demonstrated the ability of oligomeric chitosan-DNA nanoparticles to effectively transfect COS-7 cells. In rat corneas, injection of a select formulation of oligomeric chitosan-DNA nanoparticles into the stroma showed that (a) luciferase gene expression was 5.4 times greater than following administration of polyethylenimine-DNA nanoparticles; and (b) the cells that express the transgene, green fluorescent protein, were keratocytes (corneal fibroblasts). This study lays the foundation for evaluating oligomeric chitosan-DNA nanoparticles as pharmaceuticals for corneal gene therapy, a promising approach for the treatment of acquired and inherited corneal diseases that otherwise lead to blindness. Oligomeric chitosan-DNA nanoparticles can also be evaluated for the treatment of ocular diseases outside of the cornea, and for various additional gene therapy applications.; ((c) 2009 Elsevier Ltd. All rights reserved.) |
| Substance Nomenclature: | 0 (Drug Carriers); 147336-22-9 (Green Fluorescent Proteins); 9007-49-2 (DNA); 9012-76-4 (Chitosan); EC 1.13.12.- (Luciferases) |
| Entry Date(s): | Date Created: 20091103 Date Completed: 20100408 Latest Revision: 20191210 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.biomaterials.2009.10.031 |
| PMID: | 19879644 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't