钆喷替酸葡甲胺-壳聚糖颗粒载体在小鼠肠壁吸附的MRI研究

目的 探讨钆喷替酸葡甲胺(Gd-DTPA)-壳聚糖颗粒(Gd-CPs)载体在小鼠直肠壁黏附和吸收情况,实现结肠黏膜途径微粒载体的MR分子成像.方法 采用乳化-微滴融合技术合成包裹Gd-DTPA的Gd-CPs和壳聚糖颗粒(CPs).将16只小鼠以数字表法随机分为Gd-CPs和CPs组,每组8只,将Gd-CPs和CPs混悬液分别注入小鼠直肠内,于灌肠前、保留灌肠中和灌肠40 min后行直肠MR扫描.测量灌肠前后直肠壁、盆壁肌肉和图像背景MR信号强度,计算灌肠前后肠壁与盆壁肌肉的相对信号值,并采用配对t检验进行比较.结果 Gd-CPs粒径约500 nm,Gd-DTPA包裹量质量分数约30%.Gd-CPs组灌肠前后直肠壁相对信号值分别为0.84±0.06和0.98±0.09(t=4.327,P＜0.01);CPs组灌肠前后直肠壁相对信号值分别为0.83±0.04和0.84±0.05(t=0.658,P＞0.05).Gd-CPs组直肠壁信号增加率中位数为19.0%.电子显微镜示Gd-CPs颗粒位于结肠黏膜细胞内.结论 Gd-DTPA可包裹于壳聚糖微粒载体内,并可以用MRI显示载体结肠壁黏附和吸收现象,MRI是活体内监测结肠黏膜途径颗粒载体运转机制的有效技术.

In vivo imaging of colon mucosa targeted gadolinium-loaded chitosan particles in mice with MRI

Objective To synthesize a novel vector of chitosan-particles loaded with gadolinium (Gd-CPs) and observe the adhesion and absorption of the particles in the colon wall of mice with MR imaging in-vivo.Methods Chitosan particles (CPs) with and without gadolinium loaded were synthesized with the emulsion-droplet coalescence method.Sixteen mice were randomly classified into two groups.The suspension with Gd-CPs or with CPs was infused into the rectum of the 8 mice of each group,respectively.MR scans were performed before,during and 40 minutes after infusion for each mouse.Samples of the colon correlated to the enhanced area were obtained for electron microscopy examination.Signal intensity (SI) of ROIs in the wall of rectum or colon,muscles of the pelvis near the rectum and background were measured and corresponding relative SIs were calculated.Relative SI values between the two groups and pre- and post- infusion were compared with pared t test.Results Dimension of the Gd-CPs was about 500 nm,and content rate was about 30%. Values of relative SI of the rectum for pre- and post- infusion in the Gd-CPs group were 0.84±0.06 and 0.98±0.09(t=4.327,P＜0.01),respectively,while those in CPs group were 0.83±0.04 and 0.84±0.05(t=0.658.P＞0.05). The medial value of signal increase rate for CPs group was 19.0%.Gd-CPs particles were found inside the mucosal cells under the electron microscopy.Conclusion MR imaging in-vivo can reveal the phenomenon of adhesion and absorption of mucosa targeted chitosan particle carriers. Clinical MR imaging based on small animal coil is a good method to monitor colon mucosa targeted particle vectors in-vivo.