Antioxidant superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase hemeoxygenase, acetyl salicyclic acid, mannitol, captopril, Arg, or pyruvate; vitamins(lycopene, lutein, xeaxanthine, Vitamin A, carotene); administered via carotid artery or juguar vein
Inventors
Labhasetwar, Vinod D. • Reddy, Maram K.
Assignees
University of Nebraska Medical Center UNMC
Publication Number
US-8182807-B2
Publication Date
2012-05-22
Expiration Date
2024-09-30
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Abstract
The present invention relates to a method for inhibiting reperfusion injury in the brain. The method involve injecting via the carotid artery or jugular vein an antioxidant-loaded nanoparticle. A nanoparticle formulation containing an inert plasticizer is also provided for sustained release of an active agent.
Core Innovation
The invention provides a method for inhibiting reperfusion injury in the brain by administering an effective amount of an antioxidant formulated in a biodegradable nanoparticle, which is delivered via the carotid artery or jugular vein. The antioxidant can be an enzyme (such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase hemeoxygenase, or mimetic or synthetic enzymes thereof), a small molecule antioxidant (such as a vitamin antioxidant, acetyl salicylic acid, mannitol, captopril, arginine, or pyruvate), or a combination of both enzyme and small molecule antioxidants.
The nanoparticle formulation may be composed of various biodegradable polymers, such as poly(lactide-co-glycolide), poly(lactic acid), poly(alkylene glycol), polybutylcyanoacrylate, poly(methylmethacrylate-co-methacrylic acid), poly-allylamine, polyanhydride, polyhydroxybutyric acid, or polyorthoester, and may include a plasticizer (such as L-tartaric acid dimethyl ester, triethyl citrate, or glyceryl triacetate) to facilitate sustained release of the encapsulated antioxidant. Certain embodiments may contain a targeting moiety to enhance delivery to brain tissue.
The problem addressed is the susceptibility of the brain to oxidative stress following ischemia and the limitations of previous antioxidant therapies, such as poor cerebral cell penetration, unsatisfactory pharmacokinetics, and the inability to achieve sustained delivery of therapeutic agents. The inventive nanoparticle system enables sustained release, enhanced delivery across the blood-brain barrier, and localized inhibition of ischemia-induced reperfusion injury in the brain.
Claims Coverage
There is one independent claim, covering the primary inventive features of the method for inhibiting reperfusion injury in the brain using specific biodegradable nanoparticle compositions and administration routes.
Method for inhibiting reperfusion injury in the brain using an antioxidant-loaded biodegradable nanoparticle
The core inventive feature is the administration of an effective amount of an antioxidant, formulated in a biodegradable nanoparticle, via the carotid artery to a subject having cerebral ischemia. The nanoparticle provides sustained release of the antioxidant, thereby inhibiting reperfusion injury in the brain.
The independent claim establishes a method using specific delivery and formulation features to inhibit reperfusion injury in the brain, focusing on the sustained release and targeted administration of antioxidant-loaded biodegradable nanoparticles.
Stated Advantages
The nanoparticle formulation provides sustained release of the active agent, allowing for prolonged therapeutic effect.
The method enables delivery of antioxidants across the blood-brain barrier, facilitating effective brain targeting.
Antioxidant-loaded nanoparticles significantly reduce total infarct volume in the brain when administered at the time of reperfusion.
The formulation maintains blood-brain barrier integrity during reperfusion injury, protecting against endothelial damage.
Documented Applications
Prevention or reduction of ischemia/reperfusion injury in mammalian brain tissue following events such as acute head trauma, surgical occlusion of blood flow, stroke, and cardiac arrest.
Sustained and targeted delivery of antioxidants to the brain for neuroprotection during or after ischemic events.
Sustained release delivery of a wide range of active agents, including anti-infectives, antiseptics, steroids, therapeutic peptides, analgesics, anti-inflammatory agents, anticancer agents, narcotics, anesthetics, antiangiogenic agents, polysaccharides, vaccines, antigens, and nucleic acids.
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