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Pretreatment with intraluminal rapamycin nanoparticle perfusion inhibits neointimal hyperplasia in a rabbit vein graft model.

Liu K, Cao G, Zhang X, Liu R, Zou W, Wu S - Int J Nanomedicine (2010)

Bottom Line: On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3.The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China.

ABSTRACT

Purpose: Poly lactic-co-glycolic acid nanoparticles (PLGA-NP) are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP) on neointimal hyperplasia in a rabbit vein graft model.

Methods: A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP) perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.

Results: Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%). By high-performance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 μg/10 mg) 28 days after single drug perfusion.

Conclusion: Pretreatment with intraluminal RAP-PLGA-NP perfusion may inhibit neointimal hyperplasia in vein grafts by penetrating into local tissue and limiting cell proliferation.

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Related in: MedlinePlus

The flow cytometry assay for the proliferation cycles of the cells in the vein grafts and the normal vein. A) Group 1 (rapamycin-loaded PLGA nanoparticle vein graft perfusion), B) Group 2 (empty vehicle), C) Group 3 (vein graft with no treatment), and D) Group 4 (sham operation, normal vein). S phase, DNA synthesis phase.Abbreviation: PGLA, poly lactic-co-glycolic acid.
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f5-ijn-5-853: The flow cytometry assay for the proliferation cycles of the cells in the vein grafts and the normal vein. A) Group 1 (rapamycin-loaded PLGA nanoparticle vein graft perfusion), B) Group 2 (empty vehicle), C) Group 3 (vein graft with no treatment), and D) Group 4 (sham operation, normal vein). S phase, DNA synthesis phase.Abbreviation: PGLA, poly lactic-co-glycolic acid.

Mentions: The cell cycles of vein grafts in Groups 1 and 4 were almost stationary at the G0G1 phase (Figure 5). In Groups 2 and 3, cells in the DNA synthesis phase were significantly increased compared with Groups 1 and 4. The PI in Group 1 (n = 4) was much lower than that in Group 2 (n = 4, 21.11 ± 3.15% versus 30.35 ± 2.69%, P < 0.01) and Group 3 (n = 4, 21.11 ± 3.15% versus 33.86 ± 8.72%, P < 0.01). Even though the PI of Group 1 was lower than that of Groups 2 and 3, it was higher than that in Group 4 (21.11 ± 3.15% versus 10.99 ± 2.01%, P < 0.05). There was no significant difference in the PI between Groups 2 and 3 (30.35 ± 2.69% versus 33.86 ± 8.72%, P = 0.477).


Pretreatment with intraluminal rapamycin nanoparticle perfusion inhibits neointimal hyperplasia in a rabbit vein graft model.

Liu K, Cao G, Zhang X, Liu R, Zou W, Wu S - Int J Nanomedicine (2010)

The flow cytometry assay for the proliferation cycles of the cells in the vein grafts and the normal vein. A) Group 1 (rapamycin-loaded PLGA nanoparticle vein graft perfusion), B) Group 2 (empty vehicle), C) Group 3 (vein graft with no treatment), and D) Group 4 (sham operation, normal vein). S phase, DNA synthesis phase.Abbreviation: PGLA, poly lactic-co-glycolic acid.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2963931&req=5

f5-ijn-5-853: The flow cytometry assay for the proliferation cycles of the cells in the vein grafts and the normal vein. A) Group 1 (rapamycin-loaded PLGA nanoparticle vein graft perfusion), B) Group 2 (empty vehicle), C) Group 3 (vein graft with no treatment), and D) Group 4 (sham operation, normal vein). S phase, DNA synthesis phase.Abbreviation: PGLA, poly lactic-co-glycolic acid.
Mentions: The cell cycles of vein grafts in Groups 1 and 4 were almost stationary at the G0G1 phase (Figure 5). In Groups 2 and 3, cells in the DNA synthesis phase were significantly increased compared with Groups 1 and 4. The PI in Group 1 (n = 4) was much lower than that in Group 2 (n = 4, 21.11 ± 3.15% versus 30.35 ± 2.69%, P < 0.01) and Group 3 (n = 4, 21.11 ± 3.15% versus 33.86 ± 8.72%, P < 0.01). Even though the PI of Group 1 was lower than that of Groups 2 and 3, it was higher than that in Group 4 (21.11 ± 3.15% versus 10.99 ± 2.01%, P < 0.05). There was no significant difference in the PI between Groups 2 and 3 (30.35 ± 2.69% versus 33.86 ± 8.72%, P = 0.477).

Bottom Line: On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3.The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, People’s Republic of China.

ABSTRACT

Purpose: Poly lactic-co-glycolic acid nanoparticles (PLGA-NP) are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP) on neointimal hyperplasia in a rabbit vein graft model.

Methods: A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP) perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.

Results: Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%). By high-performance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 μg/10 mg) 28 days after single drug perfusion.

Conclusion: Pretreatment with intraluminal RAP-PLGA-NP perfusion may inhibit neointimal hyperplasia in vein grafts by penetrating into local tissue and limiting cell proliferation.

Show MeSH
Related in: MedlinePlus