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Published on: October 21, 2017
Comparative ultrastructural hepatic alterations induced by free and liposome-encapsulated mefenamic acid
Qais Bashir Jarrar1, Muhammad Nazrul Hakim1, Manraj Singh Cheema1
1a Department of Biomedical Science, Faculty of Medicine and Health Sciences , Universiti Putra Malaysia (UPM) , Serdang , Selangor , Malaysia.
Abstract:
Mefenamic acid (MFA) is used as an anti-inflammatory, antinociceptive, and antipyretic agent for treatment of a wide range of pathological disorders. While the uncertainty of its safety and the poor oral bioavailability constitute the major limiting factors of its medical use, considerable efforts including liposomal encapsulation are needed to achieve maximum therapeutic advantages. The current work was conducted to investigate the ultrastructural alterations in the liver induced by free MFA and its liposomal preparation. Female Sprague-Dawley rats were treated with daily oral doses of either free MFA or MFA entrapped in Tween 80 inoculated liposomes at the concentration of 80 mg/kg for 28 days. Ultrathin sections were prepared from biopsies taken from the liver of each member of all animals under study and subjected to examination by transmission electron microscopy. The liver of rats that were exposed to liposomal MFA showed more ultrastructural alterations than the rats treated with the free drug. While both groups of rats demonstrated sinusoidal dilatation, Kupffer cell hyperplasia, mitochondrial damage, and nuclear alterations, rats treated with liposome-encapsulated MFA induced an increase in the multiple lysosomes formation, hepatocytic steatosis, and apoptotic activity than free MFA-treated rats. The ultrastructural findings of the present study indicate that the use of liposomal MFA induces more hepatic damage than the use of free MFA.
Insights
Liposomal mefenamic acid (MFA) causes more liver damage than free MFA. This study observed increased ultrastructural alterations, including more lysosomes, steatosis, and apoptosis in rats treated with liposomal MFA.
Area of Science:
- Pharmacology
- Hepatology
- Drug Delivery Systems
Background:
- Mefenamic acid (MFA) is a widely used anti-inflammatory, antinociceptive, and antipyretic drug.
- Its clinical application is limited by safety concerns and poor oral bioavailability.
- Liposomal encapsulation is explored to enhance therapeutic benefits.
Purpose of the Study:
- To investigate and compare the liver ultrastructural changes induced by free MFA versus liposomal MFA.
- To evaluate the safety profile of liposomal MFA formulation in vivo.
Main Methods:
- Female Sprague-Dawley rats were administered daily oral doses of free MFA or liposomal MFA (80 mg/kg) for 28 days.
- Liver tissue biopsies were collected and examined using transmission electron microscopy (TEM).
- Ultrastructural alterations were analyzed and compared between treatment groups.
Main Results:
- Both free MFA and liposomal MFA induced sinusoidal dilatation, Kupffer cell hyperplasia, mitochondrial damage, and nuclear alterations.
- Liposomal MFA treatment resulted in significantly more pronounced ultrastructural changes compared to free MFA.
- Specific findings in the liposomal MFA group included increased formation of multiple lysosomes, hepatocytic steatosis, and apoptotic activity.
Conclusions:
- Liposomal encapsulation of MFA exacerbates hepatic damage compared to the free drug.
- The observed ultrastructural alterations suggest a higher degree of hepatotoxicity with liposomal MFA.
- Further research is warranted to understand the mechanisms behind the increased liver injury caused by liposomal MFA.
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