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Modified Paclitaxel-loaded Nanoparticles for Inhibition of Hyperplasia in a Rabbit Arterial Balloon Injury Model

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Abstract

Purpose

This study tested the possibility of localized intravascular infusion of positive charged paclitaxel-loaded nanoparticles (NPs) to better prevent neointimal formation in a rabbit carotid artery injury model.

Materials and Methods

NPs were prepared by oil–water emulsion/solvent evaporation technique using biodegradable poly (lactide-co-glycolide) (PLGA). A cationic surfactant, didodecyldimethylammonium bromide (DMAB), was absorbed on the NP surface by electrostatic attraction between positive and negative charges. NPs were characterized in such aspects as size, surface morphology, surface charges as well as in vitro drug release profile. Balloon injured rabbit carotid arteries were treated with single infusion of paclitaxel-loaded NP suspension and observed for 28 days. The inhibitory effects of NPs on neointima formation were evaluated as end-point.

Results

NPs showed spherical shape with a diameter ranging from 200 to 500 nm. Negatively charged PLGA NPs shifted to positive after the DMAB modification. The in vitro drug release profile showed a biphasic release pattern. Morphometric analyses on the retrieved artery samples revealed that the inhibitory effect of intima proliferation was dose-dependent. At a concentration of 30 mg ml−1, NP infusion completely inhibited intima proliferation in a rabbit vascular injury model.

Conclusions

Paclitaxel-loaded NPs with DMAB modification were proven an effective means of inhibiting proliferative response to vascular injury in a rabbit model.

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Abbreviations

CCA:

common carotid artery

DCM:

dichloromethane

DES:

drug-eluting stent

DMAB:

didodecyldimethylammonium bromide

EE:

entrapment efficiency

HE:

hematoxylin & eosin

HPLC:

high performance liquid chromatography

NP:

nanoparticle

PLGA:

Poly(dl-lactide-co-glycolide)

PVA:

polyvinyl alcohol

SEM:

scanning electron microscopy

TEM:

transmission electronic microscopy

VSMC:

vascular smooth muscle cell

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Acknowledgments

The authors are grateful to the Tianjin Natural Science Foundation project (023801311) and the NSFC of China (50473059) for funding this work. We thank Yongzhe Che (Medical College of Nankai University) for his direction and efforts in animal tests.

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Authors and Affiliations

  1. The Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, Tianjin, 300192, China

    Lin Mei, Hongfan Sun, Xu Jin, Dunwan Zhu & Cunxian Song

  2. Tianjin Medical University, Tianjin, 300070, China

    Rui Sun & Minfang Zhang

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  1. Lin Mei
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  2. Hongfan Sun
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  3. Xu Jin
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  4. Dunwan Zhu
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  7. Cunxian Song
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Correspondence to Hongfan Sun or Cunxian Song.

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Mei, L., Sun, H., Jin, X. et al. Modified Paclitaxel-loaded Nanoparticles for Inhibition of Hyperplasia in a Rabbit Arterial Balloon Injury Model. Pharm Res 24, 955–962 (2007). https://doi.org/10.1007/s11095-006-9214-z

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  • DOI: https://doi.org/10.1007/s11095-006-9214-z

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