Nanoliposome containing cyclosporine A reduced neuroinflammation responses and improved neurological activities in cerebral ischemia/reperfusion in rat.
Cyclosporine A (CsA) is known as a neuroprotective agent against cerebral ischemia/reperfusion (I/R) in animal models. However, the significant therapeutic effects of CsA have been observed in high systemic doses or manipulating the blood-brain barrier, resulting in systemic side effects and toxicity. As the liposome nanocarriers have been developed for efficient delivery of peptide and proteins, liposomal CsA (Lipo-CsA) could improve cerebral (I/R) injuries. In this study, the liposomal CsA formulation (CsA at dose of 2.5 mg/kg) was prepared to assess the brain injury outcomes in 90 min middle cerebral artery occlusion (MCAO) stroke model followed by 48 h reperfusion in treating rats. Five minutes after induction of cerebral ischemia in rats, intravenous (iv) administration of Lipo-CsA significantly (P < 0.001) recovered the infarct size, the brain edema, and the neurological activities compared to corresponding control groups following 48 h I/R. In addition, after 48 h cerebral I/R, Lipo-CsA potentially (P < 0.001) inhibited the inflammation responses including MPO activity and tumor necrosis factor-alpha level in comparison to other groups. In conclusion, the results indicate that the low dose of CsA in liposomal formulation is more effective compared to higher dose of free form of CsA in treatment of ischemic brain in rats.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.
Alireza
A
Partoazar
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Science, Poursina Street, Tehran, 1417613151, Iran.
Sanaz
S
Nasoohi
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.
Sayed M
SM
Rezayat
Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.
Kambiz
K
Gilani
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.
Shahram E
SE
Mehr
Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran university of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.
Amir
A
Amani
Experimental Medicine Research Center, Tehran University of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.
Nastaran
N
Rahimi
Experimental Medicine Research Center, Tehran University of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Poursina Street, Tehran, 1417613151, Iran.
Ahmad R
AR
Dehpour
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery; D007249:Inflammation / Q000517:prevention & control; D008081:Liposomes; D008297:Male; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D020521:Stroke / Q000517:prevention & control; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008081:Liposomes; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine; D009195:Peroxidase
cyclosporine A; inflammation; nanoliposome; stroke