Highly effective dendrimer-drug based compositions and methods for treatment have been developed that target neuroinflammation both in the brain and the retina upon intravenous administration. The nanodevices overcome the blood-brain barrier (BBB) and deliver drugs to target cells (activated microglia and astrocytes) producing dramatic therapeutic improvements.
Benefits:
Many promising pharmaceutical compounds fail to reach target tissue or fail to remain in the target area long enough to work. The drug-dendrimer nanoparticles invented at WSU allow the drug to be carried to target area and selectively taken up by activated cells for tailored release of drug at the target site through linkages designed into the nanoparticle. Non-toxic PAMAM Dendrimers are cleared by the kidney. Specific bioactive agents tested include an anti-oxidant/anti-inflammatory agent N-acetyl-l-cysteine (NAC) for neuroinflammation and an approved corticosteroid, Fluocinolone Acetonide (FA), for retinal degeneration. This method can be used with a variety of biological agents including drugs or imaging agents that would benefit from improved formulations to improve delivery and reduce cytotoxicity.
Stage of Development:
• Pre-Clinical
Applications:
• Ocular diseases including macular degeneration, diabetic retinopathy and retinitis pigmentosa
• Neuro-degenerative diseases: Cerebral Palsy, Multiple Sclerosis, ALS, Parkinson’s disease, Alzheimers
• Imaging agents (MRI, PET, Fluorescence)
Data Availability:
Two different animal models have shown effectiveness of nanoparticle delivery compared to drug delivery alone. Intravenous injection of dendrimer-NAC nanoparticle in newborn rabbit kits with cerebral palsy show the nanoparticles can cross the blood brain barrier and treat cerebral palsy in rabbits with significant uptake by activated microglia and astrocytes in the brain, leading to dramatic and unexpected improvements in motor function upon post-natal treatment. Intra-vitreal injection of dendrimer-FA nanoparticles into rats show preferential localization within the outer retina for sustained release and uptake by activated inner-retinal microglial cells, leading to significant neuroprotection for at least one month.
References:
1) “Dendrimer-based Targeted Intravitreal Therapy for Sustained Attenuation of Neuroinflammation in Retinal Degeneration” Biomaterials 33 (2012) 979-988
2) “Dendrimer-based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model” Sci. Transl. Med. Vol 4 #130 (2012) 1-11
News Highlights:
http://www.nature.com/news/nanomaterials-offer-hope-for-cerebral-palsy-1.10475
http://www.sciencemag.org/content/336/6079/286.summary
http://www.sciencedaily.com/releases/2011/12/111213144719.htm
Patent Status:
Multiple Patents Pending
Related Tech IDs:
07-852 / 09-945 / 10-978