Application of liposomes incorporating doxorubicin with sialyl Lewis X to prevent stenosis after rat carotid artery injury.
Restenosis remains a serious complication that can occur after angioplasty. This study investigated the efficiency of an active targeting chemotherapy using liposomes, including doxorubicin, whose surface was decorated with sialyl Lewis X (SLX) (Dox-Lipo-SLX) to prevent stenosis after angioplasty. Its delivery was controlled via the affinity between SLX and E-selectin proteins, which are expressed on vessel walls with injury. In vitro experiments confirmed the accumulation of doxorubicin as a consequence of Dox-Lipo-SLX adhering to E-selectin-positive cells. Significant doxorubicin accumulation was observed on injured vessel walls in rats treated with Dox-Lipo-SLX. In contrast, there was little accumulation using free doxorubicin or a liposome containing doxorubicin (Dox-Lipo), but without SLX. Rats were assigned to one of four groups: Dox-Lipo-SLX, Dox-Lipo, free doxorubicin, or no treatment. Dox-Lipo-SLX, Dox-Lipo, and free doxorubicin, including a dose of 0.08mg/kg doxorubicin, were intravenously administered three times in each group after angioplasty. The residual lumen area of rats in the group treated with Dox-Lipo-SLX was significantly larger than those in all other groups. These results demonstrate that an active targeting drug delivery system utilizing Dox-Lipo-SLX effectively prevents stenosis after angioplasty.
Tsuruta
Wataro
W
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Tsurushima
Hideo
H
Yamamoto
Tetsuya
T
Suzuki
Kensuke
K
Yamazaki
Noboru
N
Matsumura
Akira
A
D000800:Angioplasty, Balloon; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D019040:E-Selectin / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D008081:Liposomes; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D009844:Oligosaccharides / Q000378:metabolism*; D051381:Rats; D000080506:Sialyl Lewis X Antigen
D019040:E-Selectin; D008081:Liposomes; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D004317:Doxorubicin