Naringenin-loaded nanoparticles improve the physicochemical properties and the hepatoprotective effects of naringenin in orally-administered rats with CCl(4)-induced acute liver failure.
OBJECTIVE
A novel naringenin-loaded nanoparticles system (NARN) was developed to resolve the restricted bioavailability of naringenin (NAR) and to enhance its hepatoprotective effects in vivo on oral administration.


METHODS
Physicochemical characterizations of NARN included assessment of particle size and morphology, powder X-ray diffraction, fourier transform infrared spectroscopy, and dissolution study. In addition, to evaluate its bioactivities and its oral treatment potential against liver injuries, we compared the hepatoprotective, antioxidant, and antiapoptotic effects of NARN and NAR on carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats.


RESULTS
NARN had a significantly higher release rate than NAR and improved its solubility. NARN also exhibited more liver-protective effects compared to NAR with considerable reduction in liver function index and lipid peroxidation, in conjunction to a substantial increase in the levels of the antioxidant enzymes (P < 0.05). Moreover, NARN was able to significantly inhibit the activation of caspase-3, -8, and -9 signaling, whereas NAR only markedly inhibited caspase-3 and -9 (P < 0.05).


CONCLUSIONS
NARN effectively improved the release of NAR which resulted in more hepatoprotective effects mediated by its antioxidant and antiapoptotic properties. These observations also suggest that nanoformulation can improve the free drug's bioactivity on oral administration.
Yen
Feng-Lin
FL
Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 100, Shih-Chuan 1st Road, Kaohsiung, 807, Taiwan.
Wu
Tzu-Hui
TH
Lin
Liang-Tzung
LT
Cham
Thau-Ming
TM
Lin
Chun-Ching
CC
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride; D020169:Caspases / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers; D004789:Enzyme Activation; D044950:Flavanones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
D000975:Antioxidants; D004337:Drug Carriers; D044950:Flavanones; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D011142:Polyvinyl Alcohol; D002251:Carbon Tetrachloride; D020169:Caspases; C005273:naringenin