Intranasal Delivery of Physostigmine to
the Brain in Rabbits Bypassing the Blood Brain Barrier
Qiaolin Ren, Drug Delivery Systems
Research Laboratory
Kwon H. Kim, Department of Pharmacy
and Administrative Sciences, College of Pharmacy and Allied Health
Professions
Abstract
The objective of this research is to compare the in vivo
pharmacokinetics and brain distribution of physostigmine (PHY)
after intravenous and intranasal(IN)administration of PHY solution
and to assess the brain targeting tendency utilizing the rabbit as
an animal model. At predetermined time points, drug concentrations
in plasma, CSF and various regions of brain (olfactory bulb,
olfactory tract, cerebrum and cerebellum) were determined by LC/MS
via solid phase extraction and PK parameters were evaluated by
non-compartmental model. The brain targeting efficiencies were
measured in terms of nose-brain direct targeting percentage (DTP)
and brain targeting index (BTI). The results show that the IN
administration of PHY solution provided a significantly greater
brain targeting efficiency over the IV dosing, indicating that an
appreciable portion of the IN dose was directly transported into
the brain tissue through the olfactory pathway.