Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats
Tuba Maryam,
Nosheen Fatima Rana,
Sultan M. Alshahrani,
Farhat Batool,
Misha Fatima,
Tahreem Tanweer,
Salma Saleh Alrdahe,
Yasmene F. Alanazi,
Ifat Alsharif,
Fatima S. Alaryani,
Amer Sohail Kashif,
Farid Menaa
Affiliations
Tuba Maryam
School of Mechanical & Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Nosheen Fatima Rana
School of Mechanical & Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Sultan M. Alshahrani
Clinical Pharmacy Department, College of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia
Farhat Batool
School of Mechanical & Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Misha Fatima
School of Mechanical & Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Tahreem Tanweer
School of Mechanical & Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Salma Saleh Alrdahe
Department of Biology, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia
Yasmene F. Alanazi
Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia
Ifat Alsharif
Department of Biology, Jamoum University College, Umm Al-Qura University, Makkah 21955, Saudi Arabia
Fatima S. Alaryani
Department of Biology, College of Science, University of Jeddah, Jeddah 21589, Saudi Arabia
Amer Sohail Kashif
School of Mechanical & Manufacturing Engineering (SMME), National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan
Farid Menaa
Departments of Internal Medicine and Nanomedicine, California Innovations Corporation, 9, San Diego, CA 92037, USA
Wilson’s disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a “thin film hydration method” was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats’ spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.
