去甲基斑蝥素纳米粒大鼠体肠吸收动力学研究

目的:考察去甲基斑蝥素(NCTD)及其壳聚糖纳米粒(NCTD-CS-NP)制剂的大鼠在体吸收特征与相关动力学。方法:采用大鼠在体回流试验,并用紫外分光光度法和HPLC分别测定酚红和NCTD的质量浓度;并采用在体循环法比较不同质量浓度NCTD及NCTD-CS-NP在大鼠小肠区段内的吸收规律。结果:NCTD在十二指肠、空肠、回肠、结肠的吸收速率常数(ka)分别为:0.0306,0.0278,0.0151,0.0044h-1,NCTD-CS-NP在对应肠段的ka分别为:0.0689,0.0592,0.0353,0.0095h-1;质量浓度分别为140,160,180μg/mL的NCTD小肠ka分别为:0.0499,0.0525,0.0489h-1;对应质量浓度的NCTD-CS-NPka分别为:0.0814,0.0764,0.0734h-1。结论:NCTD的质量浓度对其大鼠全肠道的吸收无显著影响,吸收呈一级动力学过程,且以肠道中上部的吸收为主,NCTD-CS-NP可有效促进药物在肠粘膜的吸收。

Studies on Intestine Absorption in Situ of Norcantharidin Chitosan Nanoparticles in the Sprague-Dawley

Objective： To investigate the absorption character of Norcantharidin （NCTD） and Norcantharidin nanoparticles（NCTD-CS-NP） in rat intestine in situ. Methods： The intestine in rats was cannudated for in situ recirculation. UV and HPLC were used to determine the concentrations of phenol red and NCTD, respectively. The results were contrasted with NCTD and NCTD-CS-NP. The absorption character and regularity were studied at different intestine segments, and with different concentrations. Results： The absorption rate constants （ka） of NCTD at duodenum, jejunum, ileum, and colon were 0.030 6, 0.027 8, 0.015 1, 0.004 4 h^-1, respectively, and NCTD-CS-NP were 0.068 9, 0.059 2, 0.035 3, 0.009 5 h^-1. Ka of NCTD from intestine at NCTD concentration of 140, 160, 180 μg/mL were 0.049 9, 0.052 5, 0,048 9 h ^-1, respectively, and NCTD-CS-NP were 0.081 4, 0.076 4, 0.073 4 h^-1. Conclusion： The concentration of NCTD had no distinctive effect on the absorption kinetics. The absorption of NCTD was a first-order process. NCTD was well absorbed at the superior and middle segments of intestine in rats. Chitosan nanoparticles can promote the absorption of NCTD in intestinal mucosa.