The Effect of Estrogen Containing Liposome Local Delivery on the Neointimal Hyperplasia in the Rat Carotid Artery Balloon-Injury Model

Young-Sup Yoon, Yangsoo Jang, Kwang-Hoe Chung, Yong-Suk Park, Hyung Kwan Kim, Woong-Chul Kang, Jin-Wook Kwon, Bo-Young Chung, Sang-Ho Cho, Sung-Soon Kim
1998 Korean Circulation Journal  
and Objectives Estrogen has been reported to inhibit migration and proliferation of vascular smooth muscle cells in vitro and in vivo. Sustained local delivery represents a potential alternative to systemic administration because it can achieve higher tissue drug levels at site of balloon injury avoiding systemic side effects. We investigated the effect and mechanism of nanoparticulate sustained-release carrier system using liposome incorporating 17 -estradiol E 2 on neointimal formation in rat
more » ... carotid artery balloon injury model. Materials and Methods 17-estradiol benzoate, egg phosphatidylcholine, cholesterol, polyethyleneglycolphosphatidylethanolamine were mixed to produce E 2-liposome formula where the final concentrations of lipids and E 2 were 10 mg/ml and 66 M, respectively. The size of the particle was less than 200 nm. Rat carotid artery balloon injury model was used with Sprague-Dawley rats weighing 350 30g. Rats were divided into 3 groups of saline n 22 , liposome n 46 and E 2-liposome n 46 and received 0.2 ml of each agent at injured site. 1) Rats from all groups were sacrificed at 7 n 4 , 14 n 6 , and 21 n 12 days after injury, respectively. Morphometric analysis was performed for calculating medial area, neointimal area and I/M intimal area/medial area ratio 2) Rats from liposome and E 2-liposome groups received 100 mg/kg of 5bromo-2 -deoxyuridine BrdU at 25, 9 and 1hr before sacrifice at 1 n 4 , 3 n 4 , 7 n 4 , and 14 n 4 days after injury. BrdU and proliferating cell nuclear antigen PCNA stains were performed to elucidate a mechanism of inhibitory effect of E 2. Results 1 There was no increase in the neointimal area in liposome group compared with saline group at 7, 14, and 21 days after injury, respectively. 2 There was 17%, 30%, and 34% reduction of I/M ratio in E 2 -liposome group compared with liposome group at 7, 14 and 21 days after
doi:10.4070/kcj.1998.28.8.1357 fatcat:36f23iial5a6fpt2jmhqwtbq7u