Lu Jun-Jun, Wu Zheng-Hong, Ping Qi-Neng
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Yao Xue Xue Bao. 2009 Feb;44(2):197-202.
To study the solubilization of breviscapine with polyamidoamine (PAMAM) dendrimers and probe the solubilizing mechanism and investigate the influence of PAMAM dendrimers on the pharmacokinetics of breviscapine, the solubilization of breviscapine by PAMAM dendrimers of generations G1, G1.5, G2 and G2.5 with different concentrations were determined and compared in different pH conditions. Twelve rats randomized into 2 groups were separately orally administered breviscapine and breviscapine combining with PAMAM. Drug in plasma was extracted and determined with HPLC. In pH condition lower than 7.0, the solubilization of breviscapine by PAMAM dendrimers enhanced as the generation and concentration of PAMAM dendrimers as well as the pH increased. Its solubilizing mechanism involves an electrostatic interaction between the carboxyl group of breviscapine and the primary amines and tertiary amines of PAMAM dendrimers. The pharmacokinetics parameters Cmax and AUC0-8 h of breviscapine were (119.65 +/- 9.36) ng x mL(-1) and (370.09 +/- 63.08) ng x h x mL(-1). For breviscapine combined with PAMAM dendrimers, the Cmax and AUC0-8 h were (518.17 +/- 17.07) ng x mL(-1) and (1,219.47 +/- 201.87) ng x h x mL(-1), respectively. There were significant differences of AUC0-8 h between breviscapine and breviscapine combined with PAMAM dendrimers (P < 0.01). PAMAM dendrimers can greatly increase the solubility of breviscapine in water and can improve the oral bioavailability of breviscapine significantly.
为研究灯盏花素与聚酰胺-胺（PAMAM）树枝状大分子的增溶作用，探究其增溶机制，并考察PAMAM树枝状大分子对灯盏花素药代动力学的影响，测定并比较了不同浓度的第G1、G1.5、G2和G2.5代PAMAM树枝状大分子在不同pH条件下对灯盏花素的增溶作用。将12只大鼠随机分为2组，分别口服灯盏花素以及灯盏花素与PAMAM树枝状大分子的混合物。血浆中的药物经提取后用高效液相色谱法测定。在pH低于7.0的条件下，PAMAM树枝状大分子对灯盏花素的增溶作用随着PAMAM树枝状大分子的代数、浓度以及pH的升高而增强。其增溶机制涉及灯盏花素的羧基与PAMAM树枝状大分子的伯胺和叔胺之间的静电相互作用。灯盏花素的药代动力学参数Cmax和AUC0-8 h分别为(119.65±9.36) ng·mL-1和(370.09±63.08) ng·h·mL-1。对于灯盏花素与PAMAM树枝状大分子的混合物，Cmax和AUC0-8 h分别为(518.17±17.07) ng·mL-1和(1219.47±201.87) ng·h·mL-1。灯盏花素与灯盏花素和PAMAM树枝状大分子混合物之间的AUC0-8 h存在显著差异（P<0.01）。PAMAM树枝状大分子可显著提高灯盏花素在水中的溶解度，并能显著改善灯盏花素的口服生物利用度。
