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Effect of administration method, animal weight and age on the intranasal delivery
of drugs to the brain
#MMPMID28499841
Krishnan JKS
; Arun P
; Chembukave B
; Appu AP
; Vijayakumar N
; Moffett JR
; Puthillathu N
; Namboodiri AMA
J Neurosci Methods
2017[Jul]; 286
(?): 16-21
PMID28499841
show ga
BACKGROUND: The intranasal route of administration has proven to be an effective
method for bypassing the blood brain barrier and avoiding first pass hepatic
metabolism when targeting drugs to the brain. Most small molecules gain rapid
access to CNS parenchyma when administered intranasally. However, bioavailability
is affected by various factors ranging from the molecular weight of the drug to
the mode of intranasal delivery. COMPARISON WITH EXISTING METHODS: We examined
the effects of animal posture, intranasal application method and animal weight
and age on the delivery of radiolabeled pralidoxime ((3)H-2-PAM) to the brain of
rats. RESULTS: We found that using upright vs. supine posture did not
significantly affect (3)H-2-PAM concentrations in different brain regions. Older
animals with higher weights required increased doses to achieve the same drug
concentration throughout the brain when compared to young animals with lower body
weights. The use of an intranasal aerosol propelled delivery device mainly
increased bioavailability in the olfactory bulbs, but did not reliably increase
delivery of the drug to various other brain regions, and in some regions of the
brain delivered less of the drug than simple pipette administration. CONCLUSION:
In view of the emerging interest in the use of intranasal delivery of drugs to
combat cognitive decline in old age, we tested effectiveness in very old rats and
found the method to be as effective in the older rats.
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