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Title: Adventitial injection delivery of nano-encapsulated sirolimus (Nanolimus) to injury-induced porcine femoral vessels to reduce luminal restenosis
Authors: Ang, Hui Ying
Xiong, Gordon Minru
Chaw, Su Yin
Phua, Jie Liang
Ng, Jaryl Chen Koon
Wong, Philip En Hou
Venkatraman, Subbu
Chong, Tze Tec
Huang, Yingying
Keywords: Engineering::Materials
Issue Date: 2020
Source: Ang, H. Y., Xiong, G. M., Chaw, S. Y., Phua, J. L., Ng, J. C. K., Wong, P. E. H., Venkatraman, S., Chong, T. T. & Huang, Y. (2020). Adventitial injection delivery of nano-encapsulated sirolimus (Nanolimus) to injury-induced porcine femoral vessels to reduce luminal restenosis. Journal of Controlled Release, 319, 15-24.
Project: NGF-2018-05-023
Journal: Journal of Controlled Release
Abstract: Endovascular therapy in peripheral intervention has grown exponentially in the past decade, but the issue of high restenosis rates in lower extremity arteries still persist. While drug-coated balloons (DCB) have been the device of choice, recent controversary regarding the long-term safety of paclitaxel have raised concern over current DCBs. In our study, we proposed that the direct injection of a sirolimus nanoliposomal formulation (Nanolimus) using a infusion catheter can attenuate inflammation response in injured vessels. In vitro characterization showed retention of the nanoliposomes size and detectable drug amount up to 336 days in storage. For in vivo study, four female, mixed breed swines were subjected to balloon injury of the femoral arteries before treatment with either injection of saline (n = 4) or Nanolimus (n = 12) using the Bullfrog catheter. Pharmacokinetic analysis demonstrated sustained sirolimus release in the arteries and undetectable systemic drug level at 28 days. Arteries treated with Nanolimus showed significant reduction in neointima area (0.2 ± 0.3 mm2 vs 2.0 ± 1.2 mm2, p < 0.01) and luminal stenosis (14.2 ± 7.2% vs. 67.7 ± 24.8%, p < 0.01) compared to controls. In summary, adventitial delivery of sirolimus using an infusion catheter is a feasible and safe method to reduce vascular restenosis.
ISSN: 0168-3659
DOI: 10.1016/j.jconrel.2019.12.031
Rights: © 2019 Elsevier B.V. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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