China Pharmaceutical University, State Key Laboratory of Natural Medicines, School of Pharmacy, Nanjing, China.
Pharm Dev Technol. 2013 Sep-Oct;18(5):1051-7. doi: 10.3109/10837450.2011.653822. Epub 2012 Feb 5.
The potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers and oral drug delivery system was well known. Herein, we investigated the possibility of PAMAM dendrimers for promoting the solubility and oral bioavailability of puerarin. In the present study, the effect of PAMAM dendrimers with different generations (G1.5, G2, G2.5, and G3) on the solubility of puerarin was evaluated at different concentrations and pH conditions. Further more, the puerarin-G2 dendrimer complex was conducted for the in vitro hemolytic toxicity studies and pharmacokinetics studies in rats. The solubility of puerarin was significantly higher in the presence of the full generation dendrimers (e.g. G2 and G3). No significant hemolysis was observed on erythrocytes (G2, 0-2.5 mg/mL) in the hemolytic toxicity studies. The pharmacokinetics parameters Tmax, Cmax, and AUC0-8 h of puerarin suspension solution and puerarin-G2 dendrimer complex solution were 0.76 h, 1.50 µg/mL, 7.33 µg·h/mL and 0.33 h, 6.49 µg/mL, 14.02 µg·h/mL, respectively. These studies demonstrate that PAMAM dendrimers may be a promising strategy for peroral delivery of puerarin.
聚酰胺-胺（PAMAM）树枝状聚合物作为增溶剂和口服药物递送系统的潜力是众所周知的。在此，我们研究了 PAMAM 树枝状聚合物促进葛根素溶解度和口服生物利用度的可能性。在本研究中，在不同浓度和 pH 条件下，评估了不同代数（G1.5、G2、G2.5 和 G3）的 PAMAM 树枝状聚合物对葛根素溶解度的影响。此外，还对葛根素-G2 树枝状聚合物复合物进行了体外溶血毒性研究和大鼠体内药代动力学研究。在存在全代树枝状聚合物（例如 G2 和 G3）的情况下，葛根素的溶解度显著提高。在溶血毒性研究中，红细胞（G2，0-2.5mg/mL）没有观察到明显的溶血。葛根素混悬液和葛根素-G2 树枝状聚合物复合物溶液的药代动力学参数 Tmax、Cmax 和 AUC0-8h 分别为 0.76h、1.50μg/mL、7.33μg·h/mL 和 0.33h、6.49μg/mL、14.02μg·h/mL。这些研究表明，PAMAM 树枝状聚合物可能是葛根素口服递送的一种有前途的策略。
