Melatonin delivered in solid lipid nanoparticles ameliorated its neuroprotective effects in cerebral ischemia
Saba Sohail,
Fawad Ali Shah,
Shahiq uz Zaman,
Ali H. Almari,
Imran Malik,
Saifoor Ahmad Khan,
Abir Abdullah Alamro,
Alam Zeb,
Fakhar ud Din
Affiliations
Saba Sohail
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
Fawad Ali Shah
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Shahiq uz Zaman
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
Ali H. Almari
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
Imran Malik
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
Saifoor Ahmad Khan
Department of Community Medicine, Nowshera Medical College, Nowshera, Pakistan
Abir Abdullah Alamro
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia
Alam Zeb
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; Corresponding author.
Fakhar ud Din
Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Corresponding author.Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
The current study explores the potential of melatonin (MLT)-loaded solid lipid nanoparticles (MLT-SLNs) for better neuroprotective effects in ischemic stroke. MLT-SLNs were prepared using lipid matrix of palmityl alcohol with a mixture of surfactants (Tween 40, Span 40, Myrj 52) for stabilizing the lipid matrix. MLT-SLNs were tested for physical and chemical properties, thermal and polymorphic changes, in vitro drug release and in vivo neuroprotective studies in rats using permanent middle cerebral artery occlusion (p-MCAO) model. The optimized MLT-SLNs showed particle size of ∼159 nm, zeta potential of −29.6 mV and high entrapment efficiency ∼92%. Thermal and polymorphic studies showed conversion of crystalline MLT to amorphous form after its entrapment in lipid matrix. MLT-SLNs displayed a sustained release pattern compared to MLT dispersion. MLT-SLNs significantly enhanced the neuroprotective profile of MLT ascertained by reduced brain infarction, recovered behavioral responses, low expression of inflammatory markers and improved oxidation protection in rats. MLT-SLNs also showed reduced hepatotoxicity compared to p-MCAO. From these outcomes, it is evidenced that MLT-SLNs have improved neuroprotection as compared to MLT dispersion and thereby present a promising approach to deliver MLT to the brain for better therapeutic outcomes in ischemic stroke.
