Donepezil nanosuspension intended for nose to brain targeting: In vitro and in vivo safety evaluation.
The present study was to develop donepezil loaded nanosuspension for direct olfactory administration which reaches the brain and determining safety profile in Sprague-Dawley rats. Nanosuspension was prepared by ionic-crosslinking method. The developed nanosuspension was intranasally instilled into the nostrils of rats with the help of cannula (size 18/20) so that drug reached into the brain directly via nose to brain pathway. The nanosuspension had an average size of 150-200nm with a polydispersity index of 0.341. The donepezil concentration was estimated in the brain homogenate using HPLC method. The Cmax showed concentration of donepezil in brain and plasma as 7.2±0.86 and 82.8±5.42ng/ml, respectively, for drug suspension and concentration of donepezil in brain and plasma as 147.54±25.08 and 183.451±13.45ng/ml, respectively, for nanosuspension at same dose of 0.5mg/ml when administered intranasally (p<0.05). The in vivo safety evaluation studies showed that no mortality, hematological changes, body weight variations and toxicity in animals was observed, when nanosuspension was administered in different doses as compared to control group (normal saline). Donepezil loaded chitosan nanosuspension is a potential new delivery system for treatment of Alzheimer's disease, when transported via olfactory nasal pathway to the brain.
Department of Pharmaceutics, Dehradun Institute of Technology (DIT), Dehradun 248009, Uttarakhand, India.
Bhavna
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Shadab
S
Md
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Mushir
M
Ali
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Brig. S K Mazumdar Marg, Delhi 110054, India.
Rashid
R
Ali
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Brig. S K Mazumdar Marg, Delhi 110054, India.
Aseem
A
Bhatnagar
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Sanjula
S
Baboota
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India. Electronic address: jali@jamiahamdard.ac.in.
Javed
J
Ali
D000281:Administration, Intranasal; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D000077265:Donepezil; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D007189:Indans / Q000008:administration & dosage* / Q000097:blood; D049329:Nanostructures; D010880:Piperidines / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions / Q000008:administration & dosage*
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D013535:Suspensions; D000077265:Donepezil
Alzheimer's disease; Cholinesterase inhibitor; Intranasal delivery; Ionic crosslinking; Nanosuspension