Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats

Nitesh Kumar, Amita Rai, Neetinkumar D. Reddy, Rekha R. Shenoy, Jayesh Mudgal, Punit Bansal, Piya Paul Mudgal, Karthik Arumugam, Nayanabhiram Udupa, Navin Sharma, Chamallamudi Mallikarjuna Rao

Research output: Contribution to journalArticle

Abstract

Background: Silymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes. Method: The liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats. Results: The conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension. Conclusion: Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.

Original languageEnglish
Pages (from-to)703-712
Number of pages10
JournalPharmacological Reports
Volume71
Issue number4
DOIs
Publication statusPublished - 01-08-2019

Fingerprint

Silymarin
Liposomes
Wistar Rats
Alcohols
Biological Availability
Amines
In Vitro Techniques
Alcoholic Intoxication
Liver
Phosphatidylcholines
Area Under Curve
Free Radicals
Sucrose
Suspensions
Anti-Inflammatory Agents
Antioxidants
Cholesterol
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

@article{a6ccaffe88db42d6aab0c1141023cc7d,
title = "Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats",
abstract = "Background: Silymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes. Method: The liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5{\%} sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats. Results: The conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension. Conclusion: Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.",
author = "Nitesh Kumar and Amita Rai and Reddy, {Neetinkumar D.} and Shenoy, {Rekha R.} and Jayesh Mudgal and Punit Bansal and Mudgal, {Piya Paul} and Karthik Arumugam and Nayanabhiram Udupa and Navin Sharma and Rao, {Chamallamudi Mallikarjuna}",
year = "2019",
month = "8",
day = "1",
doi = "10.1016/j.pharep.2019.03.013",
language = "English",
volume = "71",
pages = "703--712",
journal = "Pharmacological Reports",
issn = "1734-1140",
publisher = "Polish Academy of Sciences Publishing House",
number = "4",

}

Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats. / Kumar, Nitesh; Rai, Amita; Reddy, Neetinkumar D.; Shenoy, Rekha R.; Mudgal, Jayesh; Bansal, Punit; Mudgal, Piya Paul; Arumugam, Karthik; Udupa, Nayanabhiram; Sharma, Navin; Rao, Chamallamudi Mallikarjuna.

In: Pharmacological Reports, Vol. 71, No. 4, 01.08.2019, p. 703-712.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats

AU - Kumar, Nitesh

AU - Rai, Amita

AU - Reddy, Neetinkumar D.

AU - Shenoy, Rekha R.

AU - Mudgal, Jayesh

AU - Bansal, Punit

AU - Mudgal, Piya Paul

AU - Arumugam, Karthik

AU - Udupa, Nayanabhiram

AU - Sharma, Navin

AU - Rao, Chamallamudi Mallikarjuna

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background: Silymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes. Method: The liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats. Results: The conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension. Conclusion: Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.

AB - Background: Silymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes. Method: The liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats. Results: The conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension. Conclusion: Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.

UR - http://www.scopus.com/inward/record.url?scp=85067170931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067170931&partnerID=8YFLogxK

U2 - 10.1016/j.pharep.2019.03.013

DO - 10.1016/j.pharep.2019.03.013

M3 - Article

VL - 71

SP - 703

EP - 712

JO - Pharmacological Reports

JF - Pharmacological Reports

SN - 1734-1140

IS - 4

ER -