Albumin-based non-covalent complexes and methods of use thereof
Inventors
Assignees
Publication Number
US-12357679-B2
Publication Date
2025-07-15
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 complex may find use in delivering the hydrophobic ligand to microorganisms that have albumin-binding outer surfaces, such as a cell wall. 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.
Albumin naturally accumulates at tumors and sites of inflammation and has two hydrophobic binding sites in which it can transport a hydrophobic ligand that would normally be insoluble in water. Many microorganisms express albumin-binding moieties on the cell surface and expression of albumin-binding proteins has been shown to promote bacterial growth and virulence, which creates a need for delivery and detection approaches that exploit albumin-binding interactions and enable transport or localization of hydrophobic molecules to such microorganisms.
Claims Coverage
This section identifies 7 independent claims and extracts the main inventive features from each independent claim as stated in the patent document.
Method of forming a solution comprising a non-covalent hydrophobic molecule–albumin complex
A method comprising dissolving a hydrophobic molecule in an organic solvent ([procedural detail omitted for safety]), combining the resulting solution with an aqueous albumin solution to provide a mixture, and removing the organic solvent from the mixture to provide an aqueous solution comprising a non-covalent complex of the hydrophobic molecule and a single albumin protein.
Method of delivering a hydrophobic molecule to a microorganism cell wall
A method comprising contacting a microorganism comprising a cell wall with an aqueous solution comprising a non-covalent complex of a hydrophobic molecule and a single albumin protein, wherein the hydrophobic molecule functionally associates with the microorganism.
Method for detecting a microorganism in a sample using hydrophobic molecule–albumin complexes
A method comprising contacting the sample with an aqueous solution comprising a plurality of non-covalent complexes (each comprising a hydrophobic molecule and a single albumin protein), detecting one or more properties of the hydrophobic molecules, and determining that the microorganism is present or absent in the sample based on the detecting.
Optical detection of microorganism using carotenoid–albumin complexes and spectral profiling
A method comprising contacting the sample with a carotenoid–albumin complex, illuminating the sample with a broadband light source, collecting and analyzing transmitted light with a spectrometer, and determining presence of the detectable hydrophobic molecule bound to the microorganism based on a temporal profile at a fixed spatial point or a spatial profile at a fixed time point of UV-Vis absorption or Raman peaks.
Aqueous composition comprising a non-covalent hydrophobic molecule–albumin complex
A composition comprising an aqueous solution that includes a non-covalent complex of a hydrophobic molecule and a single albumin protein, where the hydrophobic molecule can be a carotenoid (e.g., lycopene or β-carotene), an antimicrobial, or a pharmacologically active agent.
Method to disperse aggregates of albumin
A method comprising suspending an aggregate of albumin in a solution with a pH above 8.0 and/or sonicating the suspension, wherein the aggregate is dispersed.
Method for determining antimicrobial susceptibility using hydrophobic molecule–albumin complexes
A method comprising contacting a composition comprising a microorganism with an antimicrobial, contacting that composition with an aqueous solution comprising a non-covalent complex of a hydrophobic molecule and a single albumin protein (where the hydrophobic molecule functionally associates with the microorganism), detecting one or more properties of the hydrophobic molecule, and determining antimicrobial susceptibility based on the detected property of the hydrophobic molecule.
The independent claims cover (1) methods to form aqueous, non-covalent complexes of hydrophobic molecules with single albumin proteins, (2) methods to deliver such complexes to microorganism cell walls, (3) methods and optical approaches to detect microorganisms and to determine antimicrobial susceptibility using intermolecular distance-dependent optical properties of the hydrophobic ligand, (4) aqueous compositions comprising the non-covalent complexes, and (5) methods to disperse albumin aggregates.
Stated Advantages
Provides a delivery vehicle for targeting hydrophobic molecules to microorganisms that have 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.
Effective solubilization of hydrophobic antimicrobial agents so they can be transported in aqueous solution.
Preferential transport of the antimicrobial to the pathogen and deposition of the antimicrobial agent on the surface of the pathogenic microorganism.
May reduce the minimum inhibitory concentration (MIC) of an antimicrobial when provided in complex with albumin compared to an uncomplexed control.
Hydrophobic ligand–albumin complexes may retain properties of albumin in uncomplexed form, such as solubility and controlled aggregation behavior.
A substantially dry hydrophobic ligand–albumin complex retains solubility upon reconstitution, enabling storage formats such as freeze-dried sheets or powder.
Documented Applications
Delivering a hydrophobic ligand to microorganisms that have albumin-binding outer surfaces, such as a cell wall.
Detecting microorganisms in a sample, including optical detection and resonant Raman-based detection using carotenoid-containing ligands (e.g., lycopene).
Formulation of therapeutic compositions containing hydrophobic active agents, including hydrophobic antibacterial or antifungal agents, for administration to an individual.
Using hydrophobic ligand–albumin complexes to enhance efficacy of antimicrobial agents and to reduce minimum inhibitory concentrations (MICs) in vitro.
Using hydrophobic ligand–albumin complexes to determine presence or absence of microorganisms in clinical samples and to predict antimicrobial susceptibility (MIC determination).
Providing aqueous assay compositions for in vitro assays and therapeutic compositions for in vivo administration, including compositions that contain antioxidants, buffers, and nutrition sources as described.
Providing kits that include compositions containing non-covalent hydrophobic molecule–albumin complexes and instructions for use.
Dispersing aggregates of albumin by suspending aggregates in solution with pH above 8.0 and/or sonicating the suspension.
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