The blood-brain barrier is a substantial obstacle for delivering
anticancer agents to
brain tumors, and new strategies for bypassing it are greatly needed for
brain-tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain and could provide an alternative to
intravenous injection and convection-enhanced delivery. We treated rats bearing intracerebral human
tumor xenografts intranasally with
GRN163, an
oligonucleotide N3'-->P5'thio-
phosphoramidate telomerase inhibitor. 3'-Fuorescein
isothiocyanate (
FITC)-labeled
GRN163 was administered intranasally every 2 min
as 6 microl drops into alternating sides of the nasal cavity over 22 min.
FITC-labeled
GRN163 was present in
tumor cells at all time points studied, and accumulation of
GRN163 peaked at 4 h after delivery. Moreover,
GRN163 delivered intranasally, daily for 12 days, significantly prolonged the median survival from 35 days in the control group to 75.5 days in the GRN163-treated group. Thus, intranasal delivery of
GRN163 readily bypassed the blood-brain barrier, exhibited favorable
tumor uptake, and inhibited
tumor growth, leading to a prolonged lifespan for treated rats compared to controls. This delivery approach appears to kill
tumor cells selectively, and no toxic effects were noted in normal brain tissue. These data support further development of intranasal delivery of
tumor-specific therapeutic agents for
brain tumor patients.