Sesamol loaded solid lipid nanoparticles: a promising intervention for control of carbon tetrachloride induced hepatotoxicity.
BACKGROUND
Sesamol, a component of sesame seed oil, exhibited significant antioxidant activity in a battery of in vitro and ex vivo tests including lipid peroxidation induced in rat liver homogenates. Latter established its potential for hepatoprotection. However, limited oral bioavailability, fast elimination (as conjugates) and tendency towards gastric irritation/toxicity (especially forestomach of rodents) may limit its usefulness. Presently, we packaged sesamol into solid lipid nanoparticles (S-SLNs) to enhance its biopharmaceutical performance and compared the efficacy with that of free sesamol and silymarin, a well established hepatoprotectant, against carbon tetrachloride induced hepatic injury in rats, post induction. A self recovery group in which no treatment was given was used to observe the self-healing capacity of liver.


METHODS
S-SLNs prepared by microemulsification method were administered to rats post-treatment with CCl4 (1 ml/kg body weight (BW) twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). Liver damage and recovery on treatment was assessed in terms of histopathology, serum injury markers (alanine aminotransferase, aspartate aminotransferase), oxidative stress markers (lipid peroxidation, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker (tumor necrosis factor alpha).


RESULTS
S-SLNs (120.30 nm) at a dose of 8 mg/kg BW showed significantly better hepatoprotection than corresponding dose of free sesamol (FS; p < 0.001). Effects achieved with S-SLNs were comparable with silymarin (SILY), administered at a dose of 25 mg/kg BW. Self recovery group confirmed absence of regenerative capacity of hepatic tissue, post injury.


CONCLUSIONS
Use of lipidic nanocarrier system for sesamol improved its efficiency to control hepatic injury. Enhanced effect is probably due to: a) improved oral bioavailability, b) controlled and prolonged effect of entrapped sesamol and iii) reduction in irritation and toxicity, if any, upon oral administration. S-SLNs may be considered as a therapeutic option for hepatic ailments as effectiveness post induction of liver injury, is demonstrated presently.
Department of Biotechnology, Panjab University, Chandigarh, 160014, India. neha.riyal@gmail.com.
Neha
N
Singh
Department of Biotechnology, Panjab University, Chandigarh, 160014, India. n_khullar@yahoo.com.
Neeraj
N
Khullar
Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India. vanditakakkar@yahoo.co.in.
Vandita
V
Kakkar
Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India. indupalkaur@yahoo.com.
Indu Pal
IP
Kaur
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids; D008297:Male; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology; D017208:Rats, Wistar; D031685:Sesamum / Q000737:chemistry*; D012838:Silymarin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D052117:Benzodioxoles; D008055:Lipids; D010636:Phenols; D010936:Plant Extracts; D020011:Protective Agents; D012838:Silymarin; C025583:sesamol; D002251:Carbon Tetrachloride; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione