Intranasal Delivery of GDNF for the Treatment of Parkinson’s Disease

Intranasal Delivery of GDNF for the Treatment of Parkinson’s Disease

Student: Mattia Migliore
Department: Pharmaceutical Sciences
Advisor: Barbara Waszczak

Abstract

Figure 1: Substantia nigra dopamine neurons ( 40x view) of a rat that was administered cationic liposomes loaded with Alexa-488 ovalbumin intranasally and sacrificed after 24hrs.

Figure 1: Substantia nigra dopamine neurons ( 40x view) of a rat that was administered cationic liposomes loaded with Alexa-488 ovalbumin intranasally and sacrificed after 24hrs.

Glial cell line-derived neurotrophic factor (GDNF) exerts a neuroprotective and a neuroregenerative effect on midbrain dopamine neurons and has been promoted as possible treatment for Parkinson’s disease (PD). However, GDNF does not cross the blood-brain barrier. Therefore, administration of GDNF is limited to direct intracerebral infusions, which require invasive surgical procedures. My project will utilize nanotechnology to develop a cationic liposomal drug-delivery system to encapsulate, and deliver GDNF to the brain non-invasively. The liposomal GDNF will be administered intranasally in order to bypass the blood-brain barrier, and to avoid systemic absorption and possible peripheral side effects.

Parkinson’s disease (PD) is a progressive neurodegenerative disease resulting from the destruction of dopaminergic neurons of the A9 nigrostriatal pathway in the midbrain.

Figure 2: Striatal section (20x view) of a rat that was administered cationic liposomes loaded with Alexa-488 ovalbumin intranasally and sacrificed after 24hrs.

Figure 2: Striatal section (20x view) of a rat that was administered cationic liposomes loaded with Alexa-488 ovalbumin intranasally and sacrificed after 24hrs.

Glial Derived Neurotrophic Factor (GDNF) is a potent neurotrophic factor which has been shown, both in vivo and in vitro, to both protect and restore dopaminergic neurons.
GDNF does not readily cross the blood-brain barrier, and therefore cannot reach its site of action. This limits its use as a therapeutic treatment and potential cure for PD.

Intranasal administration, together with nanoparticle technology, can greatly improve GDNF CNS penetration making this therapeutic potential treatment a reality.