PURPOSE: Ellagic acid (EA), a dietary antioxidant associated with poor biopharmaceutical properties, was encapsulated into poly(lactide-co-glycolide) (PLGA) and polycaprolactone (PCL) nanoparticles to improve oral bioavailability. MATERIALS AND METHODS: EA-loaded nanoparticles were prepared following emulsion-diffusion-evaporation method employing didodecyldimethyl ammonium bromide (DMAB) and polyvinyl alcohol (PVA) as stabilizers. In vitro release was investigated in phosphate buffer (pH 7.4). The in situ permeation studies were performed in rats. The antioxidant potential of the DMAB-stabilized nanoparticulate formulations was evaluated against cyclosporine A (CyA)-induced nephrotoxicity in rats. RESULTS: EA-loaded PLGA and PCL nanoparticles have been successfully prepared employing PEG 400 as co-solvent to solubilize EA. The stabilizers influenced the particle size and encapsulation efficiency. DMAB when used as stabilizer to particles of approximately 120 nm and approximately 50% encapsulation, whereas PVA led to approximately 290 nm and approximately 60% encapsulation at 5% initial loading (w/w of polymer). The in vitro release of EA from the nanoparticles followed Higuchi's square root pattern and was faster with PVA-stabilized particles in comparison to those stabilized with DMAB. From the in situ permeation studies in rats, it was evident that intestinal uptake of EA as DMAB-stabilized nanoparticles was significantly higher as compared to the sodium carboxymethyl cellulose suspension and the PVA-stabilized particles. EA and EA nanoparticles were able to prevent the CyA-induced nephrotoxicity in rats as evident by biochemical parameters as well as kidney histopathology. CONCLUSION: The present study demonstrates the potential of EA nanoparticulate formulations in the prevention of CyA-induced nephrotoxicity at three times lower dose suggesting improved oral bioavailability of EA.
PURPOSE: Ellagic acid (EA), a dietary antioxidant associated with poor biopharmaceutical properties, was encapsulated into poly(lactide-co-glycolide) (PLGA) and polycaprolactone (PCL) nanoparticles to improve oral bioavailability. MATERIALS AND METHODS: EA-loaded nanoparticles were prepared following emulsion-diffusion-evaporation method employing didodecyldimethyl ammonium bromide (DMAB) and polyvinyl alcohol (PVA) as stabilizers. In vitro release was investigated in phosphate buffer (pH 7.4). The in situ permeation studies were performed in rats. The antioxidant potential of the DMAB-stabilized nanoparticulate formulations was evaluated against cyclosporine A (CyA)-induced nephrotoxicity in rats. RESULTS: EA-loaded PLGA and PCL nanoparticles have been successfully prepared employing PEG 400 as co-solvent to solubilize EA. The stabilizers influenced the particle size and encapsulation efficiency. DMAB when used as stabilizer to particles of approximately 120 nm and approximately 50% encapsulation, whereas PVA led to approximately 290 nm and approximately 60% encapsulation at 5% initial loading (w/w of polymer). The in vitro release of EA from the nanoparticles followed Higuchi's square root pattern and was faster with PVA-stabilized particles in comparison to those stabilized with DMAB. From the in situ permeation studies in rats, it was evident that intestinal uptake of EA as DMAB-stabilized nanoparticles was significantly higher as compared to the sodium carboxymethyl cellulose suspension and the PVA-stabilized particles. EA and EA nanoparticles were able to prevent the CyA-induced nephrotoxicity in rats as evident by biochemical parameters as well as kidney histopathology. CONCLUSION: The present study demonstrates the potential of EA nanoparticulate formulations in the prevention of CyA-induced nephrotoxicity at three times lower dose suggesting improved oral bioavailability of EA.
Authors: Ming Yang; Samuel K Lai; Tao Yu; Ying-Ying Wang; Christina Happe; Weixi Zhong; Michael Zhang; Abraham Anonuevo; Colleen Fridley; Amy Hung; Jie Fu; Justin Hanes Journal: J Control Release Date: 2014-07-29 Impact factor: 9.776