Method for delivering drugs to the brain
Inventors
Rabinow, Barrett • Kipp, James E. • Gendelman, Howard
Assignees
Baxter Healthcare SA • Baxter International Inc • University of Nebraska Medical Center UNMC
Publication Number
US-9044381-B2
Publication Date
2015-06-02
Expiration Date
2024-06-15
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present invention is concerned with delivering a pharmaceutical composition to the brain of a mammalian subject for treating brain diseases or disorders. The process includes the steps of: (i) providing a dispersion of the pharmaceutical composition as particles having an average particle size of from about 150 nm to about 100 microns, and (ii) administering the dispersion to the mammalian subject for delivery to the brain of a portion of the pharmaceutical composition by cells capable of reaching the brain. The dispersion of the pharmaceutical composition as particles, for example, can be phagocytized or adsorbed by the cells prior or subsequent to administration into the mammalian subject. The dispersion of the pharmaceutical composition can be administered to the central nervous system or the vascular system. After administration, the loaded cells transport the pharmaceutical composition as particles into the brain.
Core Innovation
The invention provides a method for delivering a pharmaceutical composition to the brain of a mammalian subject, particularly for treating brain diseases or disorders. This process involves supplying the pharmaceutical composition as particles with an average particle size ranging from about 150 nm to about 100 microns. The dispersion can be contacted ex vivo with cells capable of phagocytosis, such as macrophages, monocytes, granulocytes, neutrophils, basophils, and eosinophils, enabling these cells to internalize the particles through phagocytosis or adsorption.
After allowing sufficient uptake time, the loaded cells are administered back into the mammalian subject, either into the central nervous system (such as intrathecally, intracerebrally, or epidurally), or into the vascular system. The premise is that these loaded cells can transport the pharmaceutical particles into the brain, bypassing certain biological barriers and enabling targeted drug delivery.
This invention addresses key challenges with conventional oral or parenteral administration for brain-targeted therapies. Orally administered drugs are often metabolized by the liver, reducing brain bioavailability and requiring higher or more frequent dosing, which can cause unwanted toxicity. By using cell-mediated delivery of drugs in particulate form, the method aims to enhance the amount of drug reaching the brain with potentially lower systemic exposure and toxicity.
Claims Coverage
There is one independent claim in this patent, which forms the basis for several dependent claims. The independent claim highlights multiple inventive features.
Cell-mediated delivery of pharmaceutical particle dispersion to the brain
This inventive feature consists of the following essential steps: 1. Forming a dispersion of a pharmaceutical composition as particles having an average particle size of from about 150 nm to about 150 microns, where the pharmaceutical composition comprises a therapeutic agent. 2. Isolating cells from the mammalian subject that are capable of phagocytosis, and selected from the group consisting of macrophages, monocytes, granulocytes, neutrophils, basophils, eosinophils, and combinations thereof. 3. Contacting these cells with the dispersion of the pharmaceutical composition. 4. Allowing for cell uptake of a portion of the particles to form loaded cells. 5. Administering the loaded cells to the mammalian subject to deliver an effective amount of the pharmaceutical composition to the brain. The feature emphasizes the use of phagocytic cells isolated from the subject, preparation of particulate drug dispersions of defined size, ex vivo cell loading, and subsequent administration for targeted delivery to the brain.
The independent claim specifically protects the process of preparing a pharmaceutical composition in particulate form, loading phagocytic cells ex vivo, and using those loaded cells for effective brain drug delivery. It distinguishes over the prior art by encompassing the combination of particle size control, ex vivo cell loading, and administration for targeting drugs to the brain.
Stated Advantages
Increases the amount of drug delivered to the brain by using high packing in particulate form that macrophages can phagocytize.
Obviates liver metabolism since drug administered to the cerebrospinal fluid bypasses the systemic circulation and thus the liver.
Allows the drug to persist as an extended release depot in the cerebrospinal fluid for weeks or months.
Enables concentrated delivery of drug within brain-resident macrophages, exposing infecting organisms to higher drug amounts and improving clearance.
Permits administration of lower drug levels while increasing drug utilization within the brain, thereby reducing toxicity and cost of therapy.
Reduces the emergence and perpetuation of drug-resistant organisms by achieving higher local concentrations.
Documented Applications
Treating central nervous system disorders including Parkinson's disease, Alzheimer's disease, cancer, viral infection, fungal infection, bacterial infection, and spongiform encephalopathy.
Delivering anti-HIV compositions such as protease inhibitors and reverse transcriptase inhibitors to treat central nervous system HIV infection.
Using diagnostic agents, including x-ray imaging agents and contrast media, for brain imaging.
Interested in licensing this patent?