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.

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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