Acta Pharmacologica Sinica (2009) 30: 1577–1584; doi: 10.1038/aps.2009.146

Acta Pharmacologica Sinica (2009) 30: 1577–1584; doi: 10.1038/aps.2009.146

Original Article

Drug packaging and delivery using perfluorocarbon nanoparticles for targeted inhibition of vascular smooth muscle cells

Zhao-xiong ZHOU¹, Bai-gen ZHANG¹, Hao ZHANG¹, Xiao-zhong HUANG¹, Ya-li HU¹, Li SUN², Xiao-min WANG², Ji-wei ZHANG^1,*

¹Department of Vascular Surgery, Shanghai Renji Hospital , Affiliated with the Shanghai Jiaotong University School of Medicine; 2Department of Pharmacy, Shanghai 200001, China

Aim:To investigate the in vitro release profile of drugs encapsulated within perfluorocarbon (PFC) nanoparticles (NPs) and their ability to inhibit the activity of vascular smooth muscle cells (SMCs).

Methods: Dexamethasone phosphate (DxP) or dexamethasone acetate (DxA) was encapsulated into PFC nanoparticles using a high-pressure homogenous method. The morphology and size of the NPs were examined using scanning electron microscopy (SEM) and a laser particle size analyzer. Drug loading and in vitro release were assessed by high-performance liquid chromatography (HPLC). The impact of NP capsules on SMC proliferation, migration and apoptosis in vitro was assessed using cell counting kit-8, transwell cell migration and flow cytometry assays.

Results: The sizes of DxP-NPs and DxA-NPs were 224±6 nm and 236±9 nm, respectively. The encapsulation efficiency (EE) of DxP-NPs was 66.4%±1.0%, with an initial release rate of 77.2%, whereas the EE of DxA-NPs was 95.3%±1.3%, with an initial release rate of 23.6%. Both of the NP-coated drugs could be released over 7 d. Human umbilical artery SMCs were harvested and cultured for four to six passages. Compared to free DxP, SMCs treated with tissue factor (TF)-directed DxP-NPs showed significant differences in the inhibition of proliferation, migration and apoptosis (P<0.05).

Conclusion: The results collectively suggest that PFC nanoparticles will be beneficial for targeted drug delivery because of the sustained drug release and effective inhibition of SMC proliferation and migration.

Keywords: fluorocarbons; nanoparticles; restenosis; smooth muscle cells; sustained release

This work is supported by the Science and Technology Commission of Shanghai Municipality, China (0852nm05100). The authors wish to thank Professor Jennifer GAMBLE for critical review of the manuscript. We also thank the Central Research Institute of Shanghai Pharmaceutical (Group) Co for providing the high-pressure homogenizer.

* To whom correspondence should be addressed.
E-mail zhangjiwei001@sina.com
Received 2009- 0 3-25 Accepted 2009-08-27

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