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Brain targeted transcranial route of drug delivery of diazepam

Author(s): W Pathirana, S Himani Kariyawasam, Hemamali Tibbotumunuwa, K Perera
Department of Pharmacology and Pharmacy, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 08, Sri Lanka

Correspondence Address:
W Pathirana Department of Pharmacology and Pharmacy, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 08 Sri Lanka E-mail: [email protected]

The term transcranial route means the brain targeted transfer of drug molecules across the cranium through the layers of the skin and skin appendages of the head, arteries and veins of the skin of the head, the cranial bones along with the diploe, the cranial bone sutures, the meninges and specifically through the emissary veins. The administration of drugs through the scalp in ayurvedic system for the diseases associated with the brain was evaluated with a view to develop a novel targeted route for central nervous system drugs. It is expected to circumvent the systemic side effects of oral route. Diazepam was dissolved in an oil medium and applied on scalp as practiced in the ayurvedic system. Thirty rats were tested on the rotating rotarod for muscle relaxant effect of diazepam. Five groups of rats tested were the control, diazepam i.v. injected (280 µg/0.1 ml) group, two groups treated with transcranial diazepam oil solution (1.5 mg/0.2 ml) and the transcranial blank vehicle treated groups. Holding time in triplicate for each rat on the rotating rotarod was measured. The holding times following each treatment was statistically compared (one-way ANOVA). The pooled average times for the control, diazepam i.v. injected, diazepam oil solution transcranial treated two groups and the blank vehicle treated groups were 35.45, 4.73, 16.5, 15.39 and 33.23 seconds respectively. The two groups subjected to the brain targeted transcranial route showed a statistically significant decrease (50% drop) in the holding time against the control group indicating the centrally acting muscle relaxant effect due to absorption of diazepam into the brain through the proposed route.

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