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.
| Original language | English |
|---|---|
| Pages (from-to) | 1607-1616 |
| Number of pages | 10 |
| Journal | Gene Therapy |
| Volume | 9 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 2002 |
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Keywords
- Antisense oligonucleotides
- Gene therapy
- Local drug delivery
- Restenosis
- Slow release formulation
- Smooth muscle cells
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