@article {Shulman2011,
	title = {Enhancement of naringenin bioavailability by complexation with hydroxypropoyl-β-cyclodextrin},
	journal = {PLoS ONE},
	volume = {6},
	number = {4},
	year = {2011},
	note = {cited By 154},
	abstract = {The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβCD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and Cmax increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42\% and increased the rate of glucose clearance by 64\% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection. {\textcopyright} 2011 Shulman et al.},
	doi = {10.1371/journal.pone.0018033},
	url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79953748950\&doi=10.1371\%2fjournal.pone.0018033\&partnerID=40\&md5=bda9aba4a076379ad0c2544079f1ab94},
	author = {Shulman, M. and Cohen, M. and Soto-Gutierrez, A. and Yagi, H. and Wang, H. and Goldwasser, J. and Lee-Parsons, C.W. and Benny-Ratsaby, O. and Yarmush, M.L. and Nahmias, Y.}
}
