Madaan Kanika, Lather Viney, Pandita Deepti
a Department of Pharmaceutics , Jan Nayak Ch. Devi Lal Memorial College of Pharmacy , Sirsa - 125055 , Haryana , India and.
b Department of Pharmaceutical Chemistry , Jan Nayak Ch. Devi Lal Memorial College of Pharmacy , Sirsa - 125055 , Haryana , India.
Drug Deliv. 2016;23(1):254-62. doi: 10.3109/10717544.2014.910564. Epub 2014 May 20.
The aim of the present research work was to investigate the potential of polyamidoamine (PAMAM) dendrimers as oral drug delivery carriers for quercetin, a Biopharmaceutical Classification System (BCS) class II molecule. The aqueous solubility of quercetin was investigated in different generations of dendrimers, i.e. G0, G1, G2 and G3, with varying concentrations (0.1, 0.5, 1, 2 and 4 µM). Then, it was successfully incorporated in PAMAM dendrimers and they were characterized for incorporation efficacy, nature of nanoformulations, size, size distribution, surface morphology and stability. In vitro release characteristics of quercetin from all quercetin-PAMAM complexes were studied at 37 °C in phosphate buffer saline (PBS; pH 7.4). Furthermore, the efficacy of quercetin-loaded PAMAM dendrimer was assessed by pharmacodynamic experiment, namely, a carrageenan-induced paw edema model to evaluate the acute activity of this nanocarrier in response to inflammation. It was observed that both generation and the respective concentrations of PAMAM dendrimers showed potential positive effects on solubility enhancement of quercetin. All the quercetin-PAMAM complexes were found to be in nanometeric range (<100 nm) with narrow polydispersity index. In vitro study revealed a biphasic release pattern of quercetin which was characterized by an initial faster release followed by sustained release phase and pharmacodynamic study provided the preliminary proof of concept about the potential of quercetin-PAMAM complexes. The study concludes that the dendrimer-based drug delivery system for quercetin has enormous potential to resolve the drug delivery issues associated with it.
本研究工作的目的是研究聚酰胺-胺（PAMAM）树枝状大分子作为槲皮素口服给药载体的潜力，槲皮素是一种生物药剂学分类系统（BCS）II类分子。在不同代数的树枝状大分子（即G0、G1、G2和G3）中，以不同浓度（0.1、0.5、1、2和4μM）研究了槲皮素的水溶性。然后，将其成功地掺入PAMAM树枝状大分子中，并对其掺入效率、纳米制剂性质、尺寸、尺寸分布、表面形态和稳定性进行了表征。在37°C的磷酸盐缓冲盐水（PBS；pH 7.4）中研究了所有槲皮素-PAMAM复合物中槲皮素的体外释放特性。此外，通过药效学实验评估了负载槲皮素的PAMAM树枝状大分子的功效，即角叉菜胶诱导的爪肿胀模型，以评估该纳米载体对炎症的急性活性。观察到PAMAM树枝状大分子的代数和各自浓度对槲皮素的溶解度增强均显示出潜在的积极影响。发现所有槲皮素-PAMAM复合物均在纳米范围内（<100nm），具有窄的多分散指数。体外研究揭示了槲皮素的双相释放模式，其特征是初始快速释放，随后是持续释放阶段，药效学研究提供了关于槲皮素-PAMAM复合物潜力的初步概念证明。该研究得出结论，基于树枝状大分子的槲皮素给药系统在解决与其相关的药物递送问题方面具有巨大潜力。
