Polypeptide films and methods
Inventors
Assignees
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Publication Number
US-7973129-B2
Publication Date
2011-07-05
Expiration Date
Abstract
Disclosed herein are polypeptide multilayer films wherein a therapeutic agent is covalently linked to a first layer polypeptide. An advantage of such attachment is that the linked therapeutic agent can be controllably released from the multilayer film into the environment of the film upon the addition of a suitable stimulus. An advantage of the disclosed films and methods is enablement of environmentally-stimulated release under specific conditions.
Core Innovation
The invention relates to a multilayer film comprising two or more layers of polyelectrolytes with adjacent layers comprising oppositely charged polyelectrolytes. A first layer polyelectrolyte includes a first layer polypeptide having one or more first amino acid sequence motifs, where the motifs consist of 5 to 15 amino acids and have a net charge per residue greater than 0.4.
The first layer polypeptide is at least 15 amino acids long and has a balance of charge at pH 7 greater than or equal to approximately one-half of the total length of the first layer polypeptide. The first layer polypeptide comprises a therapeutic agent reversibly covalently linked to the N-terminus or the C-terminus of the first layer polypeptide, and the linkage can include configurations where sulfhydryl groups participate in a disulfide bond.
The multilayer film further includes a second layer comprising a second layer polyelectrolyte having a polycationic material or a polyanionic material with a molecular weight greater than 1,000 and at least 5 charges per molecule, where the second layer does not comprise a polypeptide. The invention also addresses assembling and functionalizing the multilayer film by disposing the second layer polyelectrolyte onto a substrate and disposing the first layer polypeptide on the second layer polyelectrolyte, thereby forming a polypeptide multilayer film.
The disclosed release behavior is controlled by adding a stimulus, notably redox conditions that enable disulfide cleavage, to trigger release from the film. The disclosed examples and demonstration describe redox-stimulated release kinetics and effects such as reduced release under oxidizing conditions and slowed release with capping bilayers.
Claims Coverage
The document includes two independent claims. Across these independent claims, the inventive content is built from a defined polypeptide motif and charge architecture, reversible covalent attachment of a therapeutic agent to the polypeptide termini, and an oppositely charged non-polypeptide polyelectrolyte second layer, with assembly by sequential deposition on a substrate.
Oppositely charged polyelectrolyte multilayer film with polypeptide first layer
A multilayer film comprising two or more layers of polyelectrolytes, wherein adjacent layers comprise oppositely charged polyelectrolytes, with a first layer polyelectrolyte including a first layer polypeptide and a second layer polyelectrolyte comprising a polycationic or polyanionic material.
Sequence motif polypeptide architecture for charge balance at pH 7
The first layer polypeptide comprises one or more first amino acid sequence motifs consisting of 5 to 15 amino acids and having a net charge per residue greater than 0.4, where the first layer polypeptide is at least 15 amino acids long and has a balance of charge at pH 7 greater than or equal to approximately one-half of the total length of the first layer polypeptide.
Reversible covalent terminal linkage of therapeutic agent to polypeptide
The first layer polypeptide comprises a therapeutic agent reversibly covalently linked to the N-terminus or the C-terminus of the first layer polypeptide.
Non-polypeptide oppositely charged second layer with defined charge density
The second layer comprises a second layer polyelectrolyte comprising a polycationic material or a polyanionic material having a molecular weight greater than 1,000 and at least 5 charges per molecule, wherein the second layer does not comprise a polypeptide.
Sequential deposition assembly of polypeptide multilayer film
A method of assembling a polypeptide multilayer film comprising disposing a second layer polyelectrolyte on a substrate wherein the second layer does not comprise a polypeptide, and disposing a first layer polypeptide on the second layer polyelectrolyte, where the first layer polypeptide has the defined amino acid sequence motifs and charge balance at pH 7.
Therapeutic agent covalently reversibly linked to polypeptide termini during assembly
In the assembling method, the first layer polypeptide comprises a therapeutic agent covalently reversibly linked to the N-terminus or the C-terminus of the first layer polypeptide.
Together, the independent claims define a multilayer film and its assembly in which a charge-balanced, motif-defined polypeptide first layer reversibly covalently links a therapeutic agent at its termini, while an oppositely charged, non-polypeptide polyelectrolyte second layer with specified molecular weight and charge per molecule completes the multilayer structure.
Stated Advantages
redox-stimulated release kinetics
reduced release under oxidizing conditions
slowed release with capping bilayers
Documented Applications
No documented applications found
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