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

H. Cohen-Sacks; Y. Najajreh; V. Tchaikovski; G. Gao; V. Elazer; R. Dahan; I. Gati; M. Kanaan; J. Waltenberger; G. Golomb

doi:10.1038/sj.gt.3301830

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

H. Cohen-Sacks, Y. Najajreh, V. Tchaikovski, G. Gao, V. Elazer, R. Dahan, I. Gati, M. Kanaan, J. Waltenberger^*, G. Golomb

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Review article › peer-review

65 Scopus citations

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	https://doi.org/10.1038/sj.gt.3301830
State	Published - Dec 2002

Keywords

Antisense oligonucleotides
Gene therapy
Local drug delivery
Restenosis
Slow release formulation
Smooth muscle cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/sj.gt.3301830

Cite this

@article{bdd6be66fb2346cf950c05b3c2dd91a6,

title = "Novel PDGFβR antisense encapsulated in polymeric nanospheres for the treatment of restenosis",

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.",

keywords = "Antisense oligonucleotides, Gene therapy, Local drug delivery, Restenosis, Slow release formulation, Smooth muscle cells",

author = "H. Cohen-Sacks and Y. Najajreh and V. Tchaikovski and G. Gao and V. Elazer and R. Dahan and I. Gati and M. Kanaan and J. Waltenberger and G. Golomb",

year = "2002",

month = dec,

doi = "10.1038/sj.gt.3301830",

language = "אנגלית",

volume = "9",

pages = "1607--1616",

journal = "Gene Therapy",

issn = "0969-7128",

publisher = "Springer Nature",

number = "23",

}

TY - JOUR

T1 - Novel PDGFβR antisense encapsulated in polymeric nanospheres for the treatment of restenosis

AU - Cohen-Sacks, H.

AU - Najajreh, Y.

AU - Tchaikovski, V.

AU - Gao, G.

AU - Elazer, V.

AU - Dahan, R.

AU - Gati, I.

AU - Kanaan, M.

AU - Waltenberger, J.

AU - Golomb, G.

PY - 2002/12

Y1 - 2002/12

N2 - 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.

AB - 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.

KW - Antisense oligonucleotides

KW - Gene therapy

KW - Local drug delivery

KW - Restenosis

KW - Slow release formulation

KW - Smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=18744410917&partnerID=8YFLogxK

U2 - 10.1038/sj.gt.3301830

DO - 10.1038/sj.gt.3301830

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???

C2 - 12424613

AN - SCOPUS:18744410917

SN - 0969-7128

VL - 9

SP - 1607

EP - 1616

JO - Gene Therapy

JF - Gene Therapy

IS - 23

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this