Abstract
A novel drug carrier for brain delivery, poly(ethyleneglycol)-poly(epsilon-caprolactone) (PEG-PCL) polymersomes conjugated with mouse-anti-rat monoclonal antibody OX26 (OX26-PO), was developed and its brain delivery property was evaluated. The diblock copolymers of methoxy-PEG-PCL and Maleimide-PEG-PCL were synthesized and applied to prepare polymersomes (PO) which were verified by direct cryogenic temperature transmission electron micrograph (Cryo-TEM) imaging. The TEM examination and dynamic light scattering results showed that OX26-PO had a round and vesicle-like shape with a mean diameter around 100 nm. Coupling of OX26 with PO was confirmed by immuno-gold labeling of OX26 visualized under the TEM and X-ray photoelectron spectroscopy test. The surface OX26 densities were obtained from enzyme-linked immunosorbant assay. The result of brain delivery in rats proved that the increase of surface OX26 density of OX26-PO decreased blood AUC. The optimized OX26 number conjugated per polymersome was 34, which can acquire the greatest blood-brain barrier (BBB) permeability surface area product and percentage of injected dose per gram brain (%ID/g brain). Furthermore, NC-1900, as a model peptide, was encapsulated into OX26(34)-PO and improved the scopolamine-induced learning and memory impairments in a water maze task via i.v. administration. These results indicated that OX26(34)-PO is a promising carrier for peptide brain delivery.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry*
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Antibodies, Monoclonal / immunology
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Area Under Curve
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Biological Availability
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Brain / metabolism*
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Coumarins / chemistry
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Coumarins / pharmacokinetics
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Cryoelectron Microscopy
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Electron Probe Microanalysis
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Lactones / chemical synthesis
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Lactones / chemistry
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Learning Disabilities / chemically induced
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Learning Disabilities / prevention & control
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Maze Learning / drug effects
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Memory Disorders / chemically induced
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Memory Disorders / prevention & control
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Microscopy, Immunoelectron
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Nanocapsules / chemistry*
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Oligopeptides / chemistry
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Oligopeptides / pharmacokinetics*
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Oligopeptides / therapeutic use
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Particle Size
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Polyesters / chemical synthesis
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Polyesters / chemistry
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Polyethylene Glycols / chemical synthesis
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Polyethylene Glycols / chemistry
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Polymers / chemical synthesis
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Polymers / chemistry*
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Pyrrolidonecarboxylic Acid / analogs & derivatives*
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Pyrrolidonecarboxylic Acid / chemistry
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Pyrrolidonecarboxylic Acid / pharmacokinetics
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Pyrrolidonecarboxylic Acid / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Receptors, Transferrin / immunology
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Scopolamine / pharmacology
Substances
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Antibodies, Monoclonal
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Coumarins
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Lactones
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NC 1900
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Nanocapsules
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Oligopeptides
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Polyesters
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Polymers
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Receptors, Transferrin
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methoxy poly(ethylene glycol-co-epsilon-caprolactone)
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poly(ethylene glycol)-block-poly(epsilon-caprolactone)
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Polyethylene Glycols
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Scopolamine
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Pyrrolidonecarboxylic Acid