The Control of Drug Release and Vascular Endothelialization after Hyaluronic Acid-Coated Paclitaxel Multi-Layer Coating Stent Implantation in Porcine Coronary Restenosis Model.
OBJECTIVE
Hyaluronic acid (HA) is highly biocompatible with cells and the extracellular matrix. In contrast to degradation products of a synthetic polymer, degradation products of HA do not acidify the local environment. The aim of this study was to fabricate an HA-coated paclitaxel (PTX)-eluting stent via simple ionic interactions and to evaluate its effects in vitro and in vivo.


METHODS
HA and catechol were conjugated by means of an activation agent, and then the stent was immersed in this solution (resulting in a HA-coated stent). After that, PTX was immobilized on the HA-coated stent (resulting in a hyaluronic acid-coated paclitaxel-eluting stent [H-PTX stent]). Study groups were divided into 4 groups: bare metal stent (BMS), HA, H-PTX, and poly (L-lactide)-coated paclitaxel-eluting stent (P-PTX). Stents were randomly implanted in a porcine coronary artery. After 4 weeks, vessels surrounding the stents were isolated and subjected to various analyses.


RESULTS
Smoothness of the surface was maintained after expansion of the stent. In contrast to a previous study on a PTX-eluting stent, in this study, the PTX was effectively released up to 14 days (a half amount of PTX in 4 days). The proliferation of smooth muscle cells was successfully inhibited (by 80.5±12.11% at 7 days of culture as compared to the control) by PTX released from the stent. Animal experiments showed that the H-PTX stent does not induce an obvious inflammatory response. Nevertheless, restenosis was clearly decreased in the H-PTX stent group (9.8±3.25%) compared to the bare-metal stent group (29.7±8.11%).


CONCLUSIONS
A stent was stably coated with PTX via simple ionic interactions with HA. Restenosis was decreased in the H-PTX group. These results suggest that HA, a natural polymer, is suitable for fabrication of drug-eluting stents (without inflammation) as an alternative to a synthetic polymer.
The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare, Gwangju, Korea.; Korea Cardiovascular Stent Research Institute, Jangsung, Korea.
In-Ho
IH
Bae
The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare, Gwangju, Korea.; Korea Cardiovascular Stent Research Institute, Jangsung, Korea.; Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
Myung Ho
MH
Jeong
Korea Cardiovascular Stent Research Institute, Jangsung, Korea.; Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
Ju Han
JH
Kim
Korea Cardiovascular Stent Research Institute, Jangsung, Korea.; Division of Cardiology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
Yong Hwan
YH
Park
The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare, Gwangju, Korea.; Korea Cardiovascular Stent Research Institute, Jangsung, Korea.
Kyung Seob
KS
Lim
The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare, Gwangju, Korea.; Korea Cardiovascular Stent Research Institute, Jangsung, Korea.
Dae Sung
DS
Park
The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare, Gwangju, Korea.; Korea Cardiovascular Stent Research Institute, Jangsung, Korea.
Jae Won
JW
Shim
The Cardiovascular Convergence Research Center of Chonnam National University Hospital, Designated by Korea Ministry of Health and Welfare, Gwangju, Korea.; Korea Cardiovascular Stent Research Institute, Jangsung, Korea.
Jung Ha
JH
Kim
Korea Cardiovascular Stent Research Institute, Jangsung, Korea.; Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
Youngkeun
Y
Ahn
Korea Cardiovascular Stent Research Institute, Jangsung, Korea.; Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
Young Joon
YJ
Hong
Korea Cardiovascular Stent Research Institute, Jangsung, Korea.; Department of Cardiology, Chonnam National University Hospital, Gwangju, Korea.
Doo Sun
DS
Sim
Coronary restenosis; Hyaluronic acid; Paclitaxel; Preclinical drug evaluation; Stents