Enhanced Antidepressant Activity of Nanostructured Lipid Carriers Containing Levosulpiride in Behavioral Despair Tests in Mice

  • Pharmaceuticals (Basel). 2023 Aug 29;16(9):1220. doi: 10.3390/ph16091220.
Sadia Tabassam Arif  1 ,  Muhammad Ayub Khan  1 ,  Shahiq Uz Zaman  1 ,  Hafiz Shoaib Sarwar  2 ,  Abida Raza  3 ,  Muhammad Sarfraz  4 ,  Yousef A Bin Jardan  5 ,  Muhammad Umair Amin  6 ,  Muhammad Farhan Sohail  7
Affiliations
  • 1. Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan.
  • 2. Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore 54000, Pakistan.
  • 3. Nanomedicine Research Laboratory, National Institute of Lasers and Optronics (NILOP), PIEAS, Islamabad 45650, Pakistan.
  • 4. College of Pharmacy, Al Ain University, Al Ain 64141, United Arab Emirates.
  • 5. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • 6. Department of Pharmaceutics and Biopharmaceutics, University of Marburg, 35032 Marburg, Germany.
  • 7. Riphah Institute of Pharmaceutical Sciences, Riphah International University Lahore Campus, Lahore 54000, Pakistan.
PMID: 37765028 DOI: 10.3390/ph16091220
Abstract

The potential of levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for enhanced antidepressant and anxiolytic effects was evaluated in the current study. A forced swim test (FST) and tail suspension test (TST) were carried out to determine the antidepressant effect whereas anxiolytic activity was investigated using light-dark box and open field tests. Behavioral changes were evaluated in lipopolysaccharide-induced depressed Animals. The access of LSP to the brain to produce therapeutic effects was estimated qualitatively by using fluorescently labeled LSP-NLCs. The distribution of LSP-NLCs was analyzed using ex vivo imaging of major organs after oral and intraperitoneal administration. Acute toxicity studies were carried out to assess the safety of LSP-NLCs in vivo. An improved antidepressant effect of LSP-NLCs on LPS-induced depression showed an increase in swimming time (237 ± 51 s) and struggling time (226 ± 15 s) with a reduction in floating (123 ± 51 s) and immobility time (134 ± 15 s) in FST and TST. The anxiolytic activity in the light-dark box and open field tests exhibited superiority over LSP dispersion. Near-infrared images of fluorescently labeled LSP-NLCs demonstrated the presence of coumarin dye in the brain after 1 h of administration. An acute toxicity study revealed no significant changes in organ-to-body weight ratio, serum biochemistry or tissue histology of major organs. It can be concluded that nanostructured lipid carriers can efficiently deliver LSP to the brain for improved therapeutic efficacy.

Keywords
acute toxicity; antidepressant; in vivo imaging; levosulpiride; nanostructured lipid carriers.
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