In vivo evaluation of 5-fluorouracil-containing self-expandable nitinol stent in rabbits: Efficiency in long-term local drug delivery.
This 5-fluorouracil (5-FU)-containing stent is fabricated by coating a film, composed of one 5-FU-containing ethylene-vinyl acetate (EVA) copolymer layer and one drug-free EVA protective layer, around a commercial self-expandable nitinol stent. The stents with various drug loadings were implanted into rabbit esophagus, and then 5-FU concentrations in the stent-touching and adjacent segments (including mucosa layer and muscle layer of each segment) of esophagus, serum, and liver were investigated throughout the experiment period. Quantitative analysis of 5-FU was performed by HPLC or LC-MS/MS, while the morphologies of esophageal mucosae by scanning electron microscopy (SEM). The results show that the 5-FU concentration in stent-touching esophageal tissue is overwhelmingly higher than that in serum or liver at all the investigation time points until 45 days. The 5-FU concentration in the stent-touching segment is higher than those in the other segments of esophagus, while the 5-FU concentration in mucosa layer is higher than that in muscle layer for the same segment. With the increase of drug loading, the drug concentrations in esophageal tissues and serum increase, and cellular desquamation of stent-touching epithelial surface become increasingly severe by SEM. Based on the results, the 5-FU-loaded esophageal stent operates long-term local drug delivery with great efficiency.
Guo
Sheng-Rong
SR
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. srguo@sjtu.edu.cn
Wang
Zhong-Min
ZM
Zhang
Ya-Qiong
YQ
Lei
Lei
L
Shi
Jing-Min
JM
Chen
Ke-Min
KM
Yu
Zhang
Z
D000497:Alloys / Q000737:chemistry; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D054855:Drug-Eluting Stents; D004947:Esophagus / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits
D000497:Alloys; D000964:Antimetabolites, Antineoplastic; C013616:nitinol; D005472:Fluorouracil