Nanoparticle Based Delivery of Quercetin for the Treatment of Carbon Tetrachloride Mediated Liver Cirrhosis in Rats.
Liver fibrosis is the common response to chronic liver injury and ultimately leads to cirrhosis. There is a pressing need in the pharmaceutical industry to develop efficient well-targeted drug delivery systems, which are lacking to date. This study was designed to investigate the efficacy of a nanoquercetin NQ; i.e., quercetin encapsulated in PAG (p-aminophenyl-1-thio-β-D-galactopryranoside)-coated NIPAAM (N-isopropyl acrylamide) nanopolymer in liver compared with naked quercetin (Q) using a carbon tetrachloride (CCl₄)-mediated liver cirrhosis model. NQ was more effective at restoring liver membrane integrity as indicated by significantly reduced serum markers, including Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH), compared with naked Q. The findings of reduced collagen and histopathology also show that the NQ effects were much better than those of naked Q. Biochemical parameters, including antioxidant defense enzymes, also provide supporting evidence. Furthermore, the decrease in NF-κB and NOS-2 expression in the NQ-treated groups was also much stronger than in the naked Q-treated group. Thus, the data clearly suggest that NQ not only provides significant hepatoprotection compared with naked Q, but it also substantially lowered the required concentration (1,000 to 10,000-fold lower) by increasing the bioavailability.
Shashi Kant
SK
Verma
Shweta
S
Rastogil
Indu
I
Arora
Kalim
K
Javed
Mohd
M
Akhtar
Mohd
M
Samim
D000178:Acrylamides / Q000737:chemistry; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride; D003094:Collagen / Q000378:metabolism; D016503:Drug Delivery Systems; D000067493:Dynamic Light Scattering; D007150:Immunohistochemistry; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009005:Monosaccharides / Q000737:chemistry; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011794:Quercetin / Q000008:administration & dosage* / Q000627:therapeutic use*; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000178:Acrylamides; D000975:Antioxidants; D009005:Monosaccharides; D016328:NF-kappa B; D017392:Thiobarbituric Acid Reactive Substances; C511682:phenyl thio-beta-D-galactopyranoside; D003094:Collagen; D011794:Quercetin; C067295:N-isopropylacrylamide; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase