Sharma G, Italia J L, Sonaje K, Tikoo K, Ravi Kumar M N V
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab, 1600 62, India.
J Control Release. 2007 Mar 12;118(1):27-37. doi: 10.1016/j.jconrel.2006.11.026. Epub 2006 Dec 6.
Ellagic acid (EA) is a potent antioxidant marketed as a nutritional supplement. Its pharmacological activity has been reported in wide variety of disease models; however its use has been limited owing to its poor biopharmaceutical properties, thereby poor bioavailability. The objective of the current study was to develop chitosan-glycerol phosphate (C-GP) in situ gelling system for sustained delivery of ellagic acid (EA) via subcutaneous route. EA was incorporated in the system employing propylene glycol (PG) and triethanolamine (TEA) as co-solvents; on the other hand EA loaded PLGA nanoparticles (np) were dispersed in the gelling system using water. These in situ gelling systems were thoroughly characterized for mechanical, rheological and swelling properties. These systems are liquid at room temperature and gels at 37 degrees C. The EA C-GP system showed an initial burst release in vitro with about 85% drug released in 12 h followed by a steady release till 160 h, on the other hand EA nanoparticles entrapped in the C-GP system displayed sustained release till 360 h. The histopathological analysis indicates the absence of inflammation on administration, suggesting that these formulations are safe during the studied period. Furthermore, the antioxidant potential of EA C-GP and EA np C-GP gels has been evaluated against cyclosporine induced nephrotoxicity in rats. The data indicates that formulations were effective against cyclosporine induced nephrotoxicity, where the EA C-GP gels showed activity at 10 times lower dose and the EA np C-GP gels at 150 times lower dose when compared to orally given EA. Formulating nanoparticles of EA and incorporating them in C-GP system results in 15 times lowering of dose in comparison EA C-GP gels which is quite significant. Together, these results indicate that the bioavailability of ellagic acid can be improved by subcutaneous formulations administered as simple EA or EA nps.
鞣花酸（EA）是一种作为营养补充剂销售的强效抗氧化剂。其药理活性已在多种疾病模型中得到报道；然而，由于其生物药剂学性质较差，从而生物利用度低，其应用受到了限制。本研究的目的是开发壳聚糖-甘油磷酸酯（C-GP）原位凝胶系统，用于通过皮下途径持续递送鞣花酸（EA）。采用丙二醇（PG）和三乙醇胺（TEA）作为助溶剂将EA加入该系统；另一方面，负载EA的聚乳酸-羟基乙酸共聚物纳米粒（np）用水分散在凝胶系统中。对这些原位凝胶系统的力学、流变学和溶胀性能进行了全面表征。这些系统在室温下为液体，在37℃时形成凝胶。EA C-GP系统在体外表现出初始突释，12小时内约85%的药物释放，随后持续释放直至160小时，另一方面，包封在C-GP系统中的EA纳米粒显示持续释放直至360小时。组织病理学分析表明给药后无炎症反应，表明这些制剂在研究期间是安全的。此外，还评估了EA C-GP和EA np C-GP凝胶对环孢素诱导的大鼠肾毒性的抗氧化潜力。数据表明，这些制剂对环孢素诱导的肾毒性有效，与口服EA相比，EA C-GP凝胶在低10倍剂量时表现出活性，EA np C-GP凝胶在低150倍剂量时表现出活性。与EA C-GP凝胶相比，制备EA纳米粒并将其加入C-GP系统可使剂量降低15倍，这是相当显著的。总之，这些结果表明，通过皮下给药的简单EA或EA纳米粒制剂可以提高鞣花酸的生物利用度。
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