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Principal Investigator: Alexander Komin
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2019
Award: $35,908
Funding agency: National Institute of Neurological Disorders and Stroke
Project Summary
The drug therapies against the central nervous system (CNS) disorders, such as brain cancer, stroke and
Alzheimer's disease, are very limited because of the challenges associated with delivering drugs across the
blood-brain barrier (BBB) into the brain. There is a need to develop novel strategies to enhance the delivery of
CNS drugs. We have identified a peptide, called the CL peptide, that demonstrates an ability to deliver a
small-molecule cargo across a model endothelial barrier. However, little is known about the biophysical
properties of this peptide that give it the barrier-penetrating property. In this project, we propose to investigate
the biophysical parameters for the peptide-based barrier penetration by working at the intersection of peptide
engineering, membrane biophysics, in vitro BBB model development, and microfluidic device design. In Aim 1,
we propose to investigate the sequence and secondary structure requirements for the high transcellular
transport with the long-term goal of developing design rules for the barrier-penetrating peptides. We will
synthesize variants of the CL peptide to test the effect of peptide's charge, hydrophobicity, and amphipathicity
on transcellular transport rate. In Aim 2, we propose to use a microfluidic device and confocal microscopy to
measure the individual rates of the peptide variants' entry and exit out of cells. We will test the hypothesis that
the barrier-penetrating properties are associated with higher exit rates, when compared to other peptides with
low transcellular transport rates.
Terms: <Affect><Alzheimer><Alzheimer Type Dementia><Alzheimer disease><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Alzheimers disease><Amino Acids><Amphipathic Alpha Helix><Amphipathic α-Helix><Antibodies><Apical><Apoplexy><Arginine><Assay><Bioassay><Biologic Assays><Biological><Biological Assay><Biophysics><Blood - brain barrier anatomy><Blood-Brain Barrier><Brain><Brain Cancer><Brain Diseases><Brain Disorders><Brain Nervous System><Brain Vascular Accident><CNS Diseases><CNS agent><CNS disorder><Cations><Cell Body><Cell membrane><Cells><Central Nervous System Agents><Central Nervous System Diseases><Central Nervous System Disorders><Central Nervous System Drugs><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Stroke><Charge><Confocal Microscopy><Cytoplasmic Membrane><Device Designs><Drug Delivery><Drug Delivery Systems><Drug Therapy><Drugs><Encephalon><Encephalon Diseases><Endothelium><Engineering><Focused Ultrasound><Goals><Gold><Hemato-Encephalic Barrier><Hydrophobicity><In Vitro><Individual><Intracranial CNS Disorders><Intracranial Central Nervous System Disorders><Investigation><Kinetics><Knowledge><L-Arginine><Laboratories><Lipid Bilayers><Lipids><Malignant Tumor of the Brain><Malignant neoplasm of brain><Measurement><Measures><Medication><Membrane><Microfluidic Device><Microfluidic Lab-On-A-Chip><Microfluidic Microchips><Modeling><Penetration><Peptides><Performance><Permeability><Pharmaceutic Preparations><Pharmaceutical Preparations><Pharmacotherapy><Plasma Membrane><Polymers><Primary Senile Degenerative Dementia><Property><Scientist><Series><Stroke><Structure><Tail><Testing><Variant><Variation><Work><alpha helix><aminoacid><base><biophysical characteristics><biophysical characterization><biophysical foundation><biophysical measurement><biophysical parameters><biophysical principles><biophysical properties><biophysical sciences><brain attack><centrally acting drug><cerebral vascular accident><cerebrovascular accident><clinical translation><dementia of the Alzheimer type><design><designing><drug treatment><drug/agent><experiment><experimental research><experimental study><fight against><fluorophore><iPS><iPSC><iPSCs><improved><induced pluripotent stem cell><lipid bilayer membrane><membrane structure><microfluidic chip><model development><nano particle><nano-sized particle><nanoparticle><nanosized particle><new approaches><novel><novel approaches><novel strategies><novel strategy><peptide drug><plasmalemma><poly(L-arginine)><polyarginine><primary degenerative dementia><senile dementia of the Alzheimer type><small molecule><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic peptide><α-helix>