Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells

Nitesh Kumar, Amita Rai, Neetinkumar D. Reddy, P. Vasanth Raj, Prateek Jain, Praful Deshpande, Geetha Mathew, N. Gopalan Kutty, Nayanabhirama Udupa, C. Mallikarjuna Rao

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background Silymarin, a hepatoprotective agent, has poor oral bioavailability. However, the current dosage form of the drug does not target the liver and inflammatory cells selectively. The aim of the present study was to develop lecithin-based carrier system of silymarin by incorporating phytosomal-liposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection. Methods The formulation was prepared by film hydration method. Release of drug was assessed at pH 1.2 and 7.4. Formulation was assessed for in vitro hepatoprotection on Chang liver cells, lipopolysaccharide-induced reactive oxygen species (ROS) production by RAW 267.4 (murine macrophages), in vivo efficacy against paracetamol-induced hepatotoxicity and pharmacokinetic study by oral route in Wistar rat. Results The formulation showed maximum entrapment (55%) for a lecithin-cholesterol ratio of 6:1. Comparative release profile of formulation was better than silymarin at pH 1.2 and pH 7.4. In vitro studies showed a better hepatoprotection efficacy for formulation (one and half times) and better prevention of ROS production (ten times) compared to silymarin. In in vivo model, paracetamol showed significant hepatotoxicity in Wistar rats assessed through LFT, antioxidant markers and inflammatory markers. The formulation was found more efficacious than silymarin suspension in protecting the liver against paracetamol toxicity and the associated inflammatory conditions. The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension. Conclusions Incorporating the phytosomal form of silymarin in liposomal carrier system increased the oral bioavailability and showed better hepatoprotection and better anti-inflammatory effects compared with silymarin suspension.

Original languageEnglish
Pages (from-to)788-798
Number of pages11
JournalPharmacological Reports
Volume66
Issue number5
DOIs
Publication statusPublished - 2014

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Silymarin
Liposomes
Biological Availability
Hepatocytes
Acetaminophen
Suspensions
Lecithins
Liver
Wistar Rats
Reactive Oxygen Species
silybin
Dosage Forms
Lipopolysaccharides
Anti-Inflammatory Agents
Pharmacokinetics
Antioxidants
Macrophages
Cholesterol

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Kumar, Nitesh ; Rai, Amita ; Reddy, Neetinkumar D. ; Raj, P. Vasanth ; Jain, Prateek ; Deshpande, Praful ; Mathew, Geetha ; Kutty, N. Gopalan ; Udupa, Nayanabhirama ; Rao, C. Mallikarjuna. / Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells. In: Pharmacological Reports. 2014 ; Vol. 66, No. 5. pp. 788-798.
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abstract = "Background Silymarin, a hepatoprotective agent, has poor oral bioavailability. However, the current dosage form of the drug does not target the liver and inflammatory cells selectively. The aim of the present study was to develop lecithin-based carrier system of silymarin by incorporating phytosomal-liposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection. Methods The formulation was prepared by film hydration method. Release of drug was assessed at pH 1.2 and 7.4. Formulation was assessed for in vitro hepatoprotection on Chang liver cells, lipopolysaccharide-induced reactive oxygen species (ROS) production by RAW 267.4 (murine macrophages), in vivo efficacy against paracetamol-induced hepatotoxicity and pharmacokinetic study by oral route in Wistar rat. Results The formulation showed maximum entrapment (55{\%}) for a lecithin-cholesterol ratio of 6:1. Comparative release profile of formulation was better than silymarin at pH 1.2 and pH 7.4. In vitro studies showed a better hepatoprotection efficacy for formulation (one and half times) and better prevention of ROS production (ten times) compared to silymarin. In in vivo model, paracetamol showed significant hepatotoxicity in Wistar rats assessed through LFT, antioxidant markers and inflammatory markers. The formulation was found more efficacious than silymarin suspension in protecting the liver against paracetamol toxicity and the associated inflammatory conditions. The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension. Conclusions Incorporating the phytosomal form of silymarin in liposomal carrier system increased the oral bioavailability and showed better hepatoprotection and better anti-inflammatory effects compared with silymarin suspension.",
author = "Nitesh Kumar and Amita Rai and Reddy, {Neetinkumar D.} and Raj, {P. Vasanth} and Prateek Jain and Praful Deshpande and Geetha Mathew and Kutty, {N. Gopalan} and Nayanabhirama Udupa and Rao, {C. Mallikarjuna}",
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Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells. / Kumar, Nitesh; Rai, Amita; Reddy, Neetinkumar D.; Raj, P. Vasanth; Jain, Prateek; Deshpande, Praful; Mathew, Geetha; Kutty, N. Gopalan; Udupa, Nayanabhirama; Rao, C. Mallikarjuna.

In: Pharmacological Reports, Vol. 66, No. 5, 2014, p. 788-798.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells

AU - Kumar, Nitesh

AU - Rai, Amita

AU - Reddy, Neetinkumar D.

AU - Raj, P. Vasanth

AU - Jain, Prateek

AU - Deshpande, Praful

AU - Mathew, Geetha

AU - Kutty, N. Gopalan

AU - Udupa, Nayanabhirama

AU - Rao, C. Mallikarjuna

PY - 2014

Y1 - 2014

N2 - Background Silymarin, a hepatoprotective agent, has poor oral bioavailability. However, the current dosage form of the drug does not target the liver and inflammatory cells selectively. The aim of the present study was to develop lecithin-based carrier system of silymarin by incorporating phytosomal-liposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection. Methods The formulation was prepared by film hydration method. Release of drug was assessed at pH 1.2 and 7.4. Formulation was assessed for in vitro hepatoprotection on Chang liver cells, lipopolysaccharide-induced reactive oxygen species (ROS) production by RAW 267.4 (murine macrophages), in vivo efficacy against paracetamol-induced hepatotoxicity and pharmacokinetic study by oral route in Wistar rat. Results The formulation showed maximum entrapment (55%) for a lecithin-cholesterol ratio of 6:1. Comparative release profile of formulation was better than silymarin at pH 1.2 and pH 7.4. In vitro studies showed a better hepatoprotection efficacy for formulation (one and half times) and better prevention of ROS production (ten times) compared to silymarin. In in vivo model, paracetamol showed significant hepatotoxicity in Wistar rats assessed through LFT, antioxidant markers and inflammatory markers. The formulation was found more efficacious than silymarin suspension in protecting the liver against paracetamol toxicity and the associated inflammatory conditions. The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension. Conclusions Incorporating the phytosomal form of silymarin in liposomal carrier system increased the oral bioavailability and showed better hepatoprotection and better anti-inflammatory effects compared with silymarin suspension.

AB - Background Silymarin, a hepatoprotective agent, has poor oral bioavailability. However, the current dosage form of the drug does not target the liver and inflammatory cells selectively. The aim of the present study was to develop lecithin-based carrier system of silymarin by incorporating phytosomal-liposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection. Methods The formulation was prepared by film hydration method. Release of drug was assessed at pH 1.2 and 7.4. Formulation was assessed for in vitro hepatoprotection on Chang liver cells, lipopolysaccharide-induced reactive oxygen species (ROS) production by RAW 267.4 (murine macrophages), in vivo efficacy against paracetamol-induced hepatotoxicity and pharmacokinetic study by oral route in Wistar rat. Results The formulation showed maximum entrapment (55%) for a lecithin-cholesterol ratio of 6:1. Comparative release profile of formulation was better than silymarin at pH 1.2 and pH 7.4. In vitro studies showed a better hepatoprotection efficacy for formulation (one and half times) and better prevention of ROS production (ten times) compared to silymarin. In in vivo model, paracetamol showed significant hepatotoxicity in Wistar rats assessed through LFT, antioxidant markers and inflammatory markers. The formulation was found more efficacious than silymarin suspension in protecting the liver against paracetamol toxicity and the associated inflammatory conditions. The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension. Conclusions Incorporating the phytosomal form of silymarin in liposomal carrier system increased the oral bioavailability and showed better hepatoprotection and better anti-inflammatory effects compared with silymarin suspension.

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DO - 10.1016/j.pharep.2014.04.007

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