Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient
Poly(amidoamine) (PAMAM) dendritic nanostructures for controlled site-specific delivery of acidic anti-inflammatory active ingredient
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DOI：
10.1208/pt060367
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发表时间：
2005-01-01
影响因子：
3.3
通讯作者：
Jain, NK
中科院分区：
文献类型：
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作者：
Asthana, A;Chauhan, AS;Jain, NK
本研究的目的是评价聚酰胺-胺（PAMAM）树枝状大分子作为纳米级药物释放单元用于控制释放水不溶性和酸性抗炎药物的潜力。选择氟比洛芬（FB）作为模型酸性抗炎药。制备不同浓度的4.0代（G）PAMAM树枝状大分子的水溶液，并进一步用于增溶FB。通过傅立叶变换红外光谱对树枝状大分子复合物的形成进行了表征。考察了pH对FB在树枝状大分子中溶解度的影响。进一步评估树枝状聚合物制剂的体外释放研究和溶血毒性。在雄性白化病大鼠中研究了药代动力学和生物分布。通过角叉菜胶诱导的爪水肿模型测试树枝状聚合物制剂的功效。观察到负载的药物显示初始快速释放（超过40%直到第3小时），随后相当缓慢地释放。药效学研究显示在第4小时抑制75%，直到第8小时维持在50%以上。与游离药物相比，树枝状制剂的平均停留时间（MRT）和终末半衰期（THF）分别增加了2倍和3倍。因此，在树突状系统中，药物在生物系统中保留的时间更长，分布更大5倍。可以得出结论，载药树枝状聚合物不仅提高了溶解度，而且还控制了生物活性物质的递送，并在炎症部位具有局部作用。
The purpose of the investigation was to evaluate the potential of polyamidoamine (PAMAM) dendrimer as nanoscale drug delivery units for controlled release of water insoluble and acidic anti-inflammatory drug. Flurbiprofen (FB) was selected as a model acidic anti-inflammatory drug. The aqueous solutions of 4.0 generation ( G) PAMAM dendrimer in different concentrations were prepared and used further for solubilizing FB. Formation of dendrimer complex was characterized by Fourier transform infrared spectroscopy. The effect of pH on the solubility of FB in dendrimer was evaluated. Dendrimer formulations were further evaluated for in vitro release study and hemolytic toxicity. Pharmacokinetic and biodistribution were studied in male albino rats. Efficacy of dendrimer formulation was tested by carrageenan induced paw edema model. It was observed that the loaded drug displayed initial rapid release ( more than 40% till 3rd hour) followed by rather slow release. Pharmacodynamic study revealed 75% inhibition at 4th hour that was maintained above 50% till 8th hour. The mean residence time (MRT) and terminal half-life (THF) of the dendritic formulation increased by 2-fold and 3-fold, respectively, compared with free drug. Hence, with dendritic system the drug is retained for longer duration in the biosystem with 5-fold greater distribution. It may be concluded that the drug-loaded dendrimers not only enhanced the solubility but also controlled the delivery of the bioactive with localized action at the site of inflammation.