Back to Search
Start Over
Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS.
- Source :
-
Journal of drug targeting [J Drug Target] 2010 Apr; Vol. 18 (3), pp. 179-90. - Publication Year :
- 2010
-
Abstract
- Injury to the central nervous system (CNS) generally results in significant neuronal death and functional loss. In vitro experiments have demonstrated that neurotrophic factors such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and neurotrophin-4/5 (NT-4/5) can promote neuronal survival. However, delivery to the injured CNS is difficult as these large protein molecules do not efficiently cross the blood-brain barrier. Intranasal delivery of 70 microg [(125)I]-radiolabeled BDNF, CNTF, NT-4, or erythropoietin (EPO) resulted in 0.1-1.0 nM neurotrophin concentrations within 25 min in brain parenchyma. In addition, not only did these neurotrophic factors reach the CNS, they were present in sufficient concentrations to activate the prosurvival PI3Kinase/Akt pathway, even where lower levels of neurotrophic factors were measured. Currently traumatic, ischemic and compressive injuries to the CNS have no effective treatment. There is potential clinical relevancy of this method for rescuing injured CNS tissues in order to maintain CNS function in affected patients. The intranasal delivery method has great clinical potential due to (1) simplicity of administration, (2) noninvasive drug administration, (3) relatively rapid CNS delivery, (4) ability to repeat dosing easily, (5) no requirement for drug modification, and (6) minimal systemic exposure.
- Subjects :
- Administration, Intranasal
Animals
Blood-Brain Barrier metabolism
Cell Survival drug effects
Central Nervous System physiopathology
Central Nervous System Diseases drug therapy
Central Nervous System Diseases physiopathology
Male
Nerve Growth Factors administration & dosage
Nerve Growth Factors pharmacology
Neurons drug effects
Neurons metabolism
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Rats
Rats, Long-Evans
Rats, Sprague-Dawley
Time Factors
Central Nervous System metabolism
Drug Delivery Systems
Nerve Growth Factors pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1029-2330
- Volume :
- 18
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of drug targeting
- Publication Type :
- Academic Journal
- Accession number :
- 19807216
- Full Text :
- https://doi.org/10.3109/10611860903318134