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DAVID LI L A B O R A T O R Y O F M O L E C U L A R N E U R O B I O L O G Y
B O S T O N U N I V E R S I T Y S C H O O L O F M E D I C I N E
Nanoparticle Synthesis for Drug Delivery
Background
� Natural barriers between circulatory system and nervous system ¡ Central nerves: Blood-Brain Barrier (BBB) ¡ Central cerebrospinal fluid (BCSFB) ¡ Peripheral nerves: Blood-Nerve Fiber Barrier (BNFB)
http://www.nature.com/nrmicro/journal/v6/n8/images/nrmicro1952-f1.jpg
http://www.ncbi.nlm.nih.gov/books/NBK27998/
Background
� Many psychoactive drugs cannot be therapeutic ¡ Barrier impermeability ¡ Metabolism before reaching target ¡ Nonspecific perfusion
� Demand for designer therapeutics that match drug with specific delivery system
http://onlinelibrary.wiley.com/store/10.1002/adhm.201200112/asset/image_m/mcontent.jpg?
v=1&s=f8eb048c9587c3381d5e668e982b716db134fc50
http://www.hindawi.com/journals/jdd/2012/915375.fig.003.jpg
What is Nanotechnology?
� Nanotechnology is the manipulation of matter between the atomic and the cellular scale ¡ Technically 1-100nm in diameter, though can be larger ¡ Biomedical applications include visualization and drug
delivery
http://www.livenano.org/wp-content/uploads/2011/03/quantum-dots.jpg http://www.ecosox.com/nanoparticles.jpg
Relevance to Molecular Neurobiology
� Advances in biomedical engineering can be applied to research and skills in a basic research lab ¡ Effective noninvasive delivery of drugs and other substances ¡ Visualization and quantification
� Goal: Identify and explore biomaterials and drug delivery as they relate to molecular neurobiology
http://www.nature.com/nrn/journal/v10/n9/fig_tab/nrn2685_F2.html
Project Proposal
� Drugs and large molecules can be delivered to the brain from an intravenous injection ¡ Nanoparticles can cross the BBB and degrade ¡ Current issues include specific uptake by the
reticuloendothelial system
http://images.medicinenet.com/images/illustrations/lung-stomach-spleen.jpg
Project Proposal
� Two main goals ¡ Determine whether novel materials can be incorporated into
this nanoparticle structure for brain delivery ¡ Modify the particles for more efficient delivery to the brain
Possible Implications
Steroid and Drug Delivery
Alternative Alzheimer’s Model Neurogenesis Modulator Delivery
Reproducible Encapsulation
Reduce RES Uptake Modulate Drug Release Curve
Surfactant Characterization
Materials Science
Pharmacology
Steroid and Drug Delivery
� Many neuroactive steroids are not viable for therapeutics ¡ Solubility ¡ Toxicity
� Targeted nanoparticles provide an efficient vehicle for delivery
Neurogenesis Modulator Delivery
� Neurogenesis can be altered and the effects on spatial memory over time analyzed ¡ Invasive injection of rotovirus into brain ¡ Ineffective intravenous or intraperitoneal delivery
� Targeted nanoparticles can deliver large drugs or, with modification, genes
Alternative Alzheimer’s Model
� Alzheimer’s disease is a common form of dementia ¡ No known cure ¡ Formation of plaques, cause or effect unknown ¡ Causes breakdown of BBB
� Targeted nanoparticles can deliver amyloid to the brain, creating plaques and generating a new experimental model
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