Albumin-based non-covalent complexes and methods of use thereof
Inventors
Assignees
Publication Number
US-10071141-B2
Publication Date
2018-09-11
Expiration Date
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Abstract
A non-covalent complex of an albumin molecule and a hydrophobic ligand, compositions containing the same, and methods of use thereof are provided. The present complex may find use in delivering the hydrophobic ligand to microorganisms that have albumin-binding outer surfaces, such as a cell wall.
Core Innovation
A non-covalent complex of an albumin molecule and a hydrophobic ligand, compositions containing the same, and methods of use thereof are provided. The present hydrophobic ligand-albumin complexes provide a delivery vehicle for targeting a hydrophobic molecule to a microorganism, and may find use in the detection, e.g., optical detection, of microorganisms in a sample and in the formulation of therapeutic compositions containing hydrophobic active agents, e.g., hydrophobic antibacterial or antifungal agents, for administration to an individual in need thereof. Methods of making and using hydrophobic ligand-albumin complexes are provided.
Many bacterial and fungal cells produce surface proteins that bind albumin, and expression of albumin-binding proteins has been shown to promote bacterial growth and virulence. Albumin naturally accumulates at tumors and sites of inflammation and has hydrophobic binding sites that can transport hydrophobic ligands that would normally be insoluble in water. The disclosure addresses delivery and detection challenges posed by hydrophobic molecules by using non-covalent hydrophobic ligand-albumin complexes to solubilize, target, and deposit hydrophobic ligands onto albumin-binding microorganisms.
Claims Coverage
One independent claim is presented. The main inventive features relate to (i) preparing a carotenoid-albumin non-covalent complex using an organic solvent comprising a C3-C5 ketone or a combination solvent, (ii) forming an aqueous complex comprising a single albumin protein bound to the carotenoid, (iii) contacting a microorganism so the microorganism functionally associates with the carotenoid, and (iv) detecting one or more properties of the carotenoid.
Dissolving the carotenoid in a C3-C5 ketone or solvent combination
dissolving a carotenoid in: [procedural detail omitted for safety] (a first organic solvent comprising a C3-C5 ketone; or a combination of the first organic solvent and a second organic solvent) to provide a first solution.
Forming a non-covalent carotenoid–albumin complex comprising a single albumin protein
combining the first solution with a second solution to provide a third solution, wherein the second solution is an aqueous solution comprising an albumin protein; and removing the first organic solvent or the combination of the first organic solvent and the second organic solvent from the third solution to provide a fourth solution, wherein the fourth solution is an aqueous solution comprising a non-covalent complex of the carotenoid and a single albumin protein, wherein the complex does not include more than one albumin protein. [procedural detail omitted for safety]
Contacting a microorganism to functionally associate it with the carotenoid
contacting a microorganism with the fourth solution to functionally associate the microorganism with the carotenoid.
Detecting one or more properties of the carotenoid
detecting one or more properties of the carotenoid.
The independent claim is directed to preparing an aqueous, non-covalent carotenoid–albumin complex (with a single albumin protein per complex), using an organic solvent strategy, applying that complex to associate with microorganisms, and detecting carotenoid properties as an output.
Stated Advantages
Provides a delivery vehicle for targeting a hydrophobic molecule to a microorganism that has albumin-binding outer surfaces.
May be used in the detection, including optical detection, of microorganisms in a sample.
Enables formulation of therapeutic compositions containing hydrophobic active agents, including hydrophobic antibacterial or antifungal agents, for administration to an individual.
Facilitates effective solubilization of hydrophobic antimicrobial agents, preferential transport of the antimicrobial to the pathogen, and deposition of the antimicrobial agent on the surface of the pathogenic microorganism.
May enhance antimicrobial efficacy as reflected by reductions in minimum inhibitory concentration (MIC) in disclosed examples.
Documented Applications
Delivering hydrophobic ligands to microorganisms that have albumin-binding outer surfaces to localize or transfer hydrophobic molecules to a microorganism (e.g., to cell walls).
Optical detection of microorganisms in a sample, including clinical samples, using intermolecular distance-dependent optical properties of chromophore-containing hydrophobic ligands complexed with albumin.
Formulation of therapeutic compositions containing hydrophobic pharmacologically active agents (e.g., antimicrobials, anti-cancer drugs, antivirals, cardiovascular drugs) complexed with albumin for administration to an individual.
Enhancing antimicrobial efficacy and determining antimicrobial susceptibility, including rapid prediction or measurement of minimum inhibitory concentration (MIC).
Providing substantially dry (powder or sheet) hydrophobic ligand–albumin complexes that retain solubility upon reconstitution for assays or therapeutic use.
Kits comprising a composition with a non-covalent hydrophobic molecule–albumin complex and, optionally, buffers and instructional material for use.
Methods for dispersing aggregates of albumin by adjusting solution pH and applying sonication (conceptual use described).
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