A biodegradable microneedle cuff for comparison of drug effects through perivascular delivery to balloon-injured arteries

Dae Hyun Kim, Eui Hwa Jang, Kang Ju Lee, Ji Yong Lee, Seung Hyun Park, Il Ho Seo, Kang Woog Lee, Seung Hyun Lee, Won Hyoung Ryu, Young Nam Youn

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Restenosis at a vascular anastomosis site is a major cause of graft failure and is difficult to prevent by conventional treatment. Perivascular drug delivery has advantages as drugs can be diffused to tunica media and subintima while minimizing the direct effect on endothelium. This in vivo study investigated the comparative effectiveness of paclitaxel, sirolimus, and sunitinib using a perivascular biodegradable microneedle cuff. A total of 31 New Zealand white rabbits were used. Rhodamine was used to visualize drug distribution (n = 3). Sirolimus- (n = 7), sunitinib- (n = 7), and paclitaxel-loaded (n = 7) microneedle cuffs were placed at balloon-injured abdominal aortae and compared to drug-free cuffs (n = 7). Basic histological structures were not affected by microneedle devices, and vascular wall thickness of the device-only group was similar to that of normal artery. Quantitative analysis revealed significantly decreased neointima formation in all drug-treated groups (p < 0.001). However, the tunica media layer of the paclitaxel-treated group was significantly thinner than that of other groups and also showed the highest apoptotic ratio (p < 0.001). Proliferating cell nuclear antigen (PCNA)-positive cells were significantly reduced in all drug-treated groups. Sirolimus or sunitinib appeared to be more appropriate for microneedle devices capable of slow drug release because vascular wall thickness was minimally affected.

Original languageEnglish
Article number56
JournalPolymers
Volume9
Issue number2
DOIs
Publication statusPublished - 2017

Bibliographical note

Funding Information:
The authors would like to thank Dong-Su Jang, MFA, (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the illustrations. This study was supported by a faculty research grant of Yonsei University College of Medicine (6-2014-0116). This research was also financially supported by research grants of the National Research Foundation of Korea (NRF) funded by the Korean Government (MSIP) (NRF-2016R1A2B4010487) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI08C2149).

Publisher Copyright:
© 2017 by the authors.

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Polymers and Plastics

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