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Novel PDGFβR antisense encapsulated in polymeric nanospheres for the treatment of restenosis

Gene Therapy volume 9, pages 1607–1616 (2002)Cite this article

Abstract

Nanospheres composed of the biocompatible and biodegradable polymer, poly-DL-lactide/glycolide and containing platelet-derived growth factor β-receptor antisense (PDGFβR-AS) have been formulated and examined in vitro and in vivo in balloon-injured rat restenosis model. The nanospheres (~300 nm) of homogenous size distribution exhibited high encapsulation efficiency (81%), and a sustained release of PDGFβR-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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Acknowledgements

This work was supported by a trilateral research grant (Wa 734/4-1) from the Deutsche Forschungsgemeinschaft to GG, MK and JW (coordinator).

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

    H Cohen-Sacks, Y Najajreh, G Gao, V Elazer, R Dahan, I Gati & G Golomb

  2. Division of Molecular Genetics, Life Science Department, Bethlehem University, Bethlehem, Israel

    Y Najajreh & M Kanaan

  3. Department Internal Medicine II, Ulm University Medical Center, Ulm, Germany

    V Tchaikovski & J Waltenberger

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  1. H Cohen-Sacks
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Cohen-Sacks, H., Najajreh, Y., Tchaikovski, V. et al. Novel PDGFβR antisense encapsulated in polymeric nanospheres for the treatment of restenosis. Gene Ther 9, 1607–1616 (2002). https://doi.org/10.1038/sj.gt.3301830

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