nanoparticle synthesis for drug delivery...nanoparticle synthesis for drug delivery . background !...
TRANSCRIPT
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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
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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/
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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
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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
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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
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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
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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
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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
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Steroid and Drug Delivery
� Many neuroactive steroids are not viable for therapeutics ¡ Solubility ¡ Toxicity
� Targeted nanoparticles provide an efficient vehicle for delivery
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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
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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
http://www.sigmaaldrich.com/medium/structureimages/77/mfcd00056177.png