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  • Title: Novel PDGFbetaR antisense encapsulated in polymeric nanospheres for the treatment of restenosis.
    Author: Cohen-Sacks H, Najajreh Y, Tchaikovski V, Gao G, Elazer V, Dahan R, Gati I, Kanaan M, Waltenberger J, Golomb G.
    Journal: Gene Ther; 2002 Dec; 9(23):1607-16. PubMed ID: 12424613.
    Abstract:
    Nanospheres composed of the biocompatible and biodegradable polymer, poly-DL-lactide/glycolide and containing platelet-derived growth factor beta-receptor antisense (PDGFbetaR-AS) have been formulated and examined in vitro and in vivo in balloon-injured rat restenosis model. The nanospheres (approximately 300 nm) of homogenous size distribution exhibited high encapsulation efficiency (81%), and a sustained release of PDGFbetaR-AS (phosphorothioated). Cell internalization was visualized, and the inhibitory effect on SMC was observed. Partially phosphorothioated antisense sequences were found to be more specific than the fully phosphorothioated analogs. A significant antirestenotic effect of the naked AS sequence and the AS-NP (nanoparticles) was observed in the rat carotid in vivo model. The extent of mean neointimal formation 14 days after injection of AS-NP, measured as a percentage of luminal stenosis, was 32.21 +/- 4.75% in comparison to 54.89 +/- 8.84 and 53.84 +/- 5.58% in the blank-NP and SC-NP groups, respectively. It is concluded that PLGA nanospheres containing phosphorothioated oligodeoxynucleotide antisense could serve as an effective gene delivery systems for the treatment of restenosis.
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