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  • Title: Biodegradable in situ gelling system for subcutaneous administration of ellagic acid and ellagic acid loaded nanoparticles: evaluation of their antioxidant potential against cyclosporine induced nephrotoxicity in rats.
    Author: Sharma G, Italia JL, Sonaje K, Tikoo K, Ravi Kumar MN.
    Journal: J Control Release; 2007 Mar 12; 118(1):27-37. PubMed ID: 17258836.
    Abstract:
    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.
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