Periadventitial application of rapamycin-loaded nanoparticles produces sustained inhibition of vascular restenosis

Author

Xudong Shi, Guojun Chen, Lian Wang Guo, Yi Si, Men Zhu, Srikanth Pilla, Bo Liu, Shaoqin Gong, K. Craig Kent

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions. © 2014 Shi et al.

Original language	English
Article number	e89227
Journal	PLoS One
Volume	9
Issue number	2
DOIs	http://dx.doi.org/10.1371/journal.pone.0089227
State	Published - Feb 21 2014
Externally published	Yes

• Link to publication in Scopus
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PMID: 24586612

PMCID: PMC3931710

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Sirolimus Nanoparticles Blood Vessels Poloxamer Tunica IntimaGels Hyperplasia Ribosomal Protein S6 Kinases Polyglactin 910 Wounds and Injuries

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Standard

Periadventitial application of rapamycin-loaded nanoparticles produces sustained inhibition of vascular restenosis. / Shi, Xudong; Chen, Guojun; Guo, Lian Wang; Si, Yi; Zhu, Men; Pilla, Srikanth; Liu, Bo; Gong, Shaoqin; Kent, K. Craig.

In: PLoS One, Vol. 9, No. 2, e89227, 21.02.2014.

Research output: Contribution to journal › Article

Harvard

Shi, X, Chen, G, Guo, LW, Si, Y, Zhu, M, Pilla, S, Liu, B, Gong, S & Kent, KC 2014, 'Periadventitial application of rapamycin-loaded nanoparticles produces sustained inhibition of vascular restenosis' PLoS One, vol 9, no. 2, e89227. DOI: 10.1371/journal.pone.0089227

APA

Shi, X., Chen, G., Guo, L. W., Si, Y., Zhu, M., Pilla, S., ... Kent, K. C. (2014). Periadventitial application of rapamycin-loaded nanoparticles produces sustained inhibition of vascular restenosis. PLoS One, 9(2), [e89227]. DOI: 10.1371/journal.pone.0089227

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