کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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9369 | 627 | 2010 | 7 صفحه PDF | دانلود رایگان |
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, ≤98.2 ± 4.4 nm. Zeta potential measurements of oligomeric chitosan-DNA nanoparticles exhibited a strong positive charge ≥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.
Journal: Biomaterials - Volume 31, Issue 7, March 2010, Pages 1814–1820