The Uab Research Foundation (the University of Alabama at Birmingham)

Bioelastics Research, Ltd.

Other

University of Bristol

Bioelastics, Inc.

Dan W Urry

Kouji Okamoto

Kelley D Urry

David T McPherson

Jie Xu

Marianna Marshall Long

Paul Glazer

Henry Daniell

Timothy M Parker

Umamaheswara Prasad Kari

Marianna Long

Peter R Shewry

Robert M Senior

K U Prasad

U Prasad Kari

Methods to determine drug hydrophobicity and to quantify changes in drug hydrophobicity that optimize drug function by means of differential scanning calorimetry of an endothermic phase transition of a base protein-based polymer, specifically of an elastic-contractile model protein, to which is attached the drug to be evaluated for its hydrophobicity in terms of the change in Gibbs free energy for hydrophobic association, &#x394;Ghave been developed. Also described herein is the preparation of nanoparticles comprised of protein-based polymers, specifically of elastic-contractile model proteins, designed for the binding and desired release rate of a specific drug or class of drugs. Further described herein is a means of targeting the drug-laden nanoparticle to a cell by means of decorating the nanoparticle surface with a molecular entity that selectively binds to the diseased cell or disease causing organism, e.g., by decorating the drug-laden nanoparticle surface with synthetic antigen-binding fragment to an up-regulated receptor characteristic of the diseased cell.

Compositions and methods for optimizing drug hydrophobicity and drug delivery to cells

A method for tissue augmentation in a mammal is provided comprising injecting a polymer at a tissue site in need of augmentation and having a tissue temperature, the polymer comprising repeating peptide monomeric units selected from the group consisting of nonapeptide, pentapeptide and tetrapeptide monomeric units, wherein the monomeric units form a series of &bgr;-turns separated by dynamic bridging segments suspended between the &bgr;-turns, wherein the polymer has an inverse temperature transition T less than the tissue temperature, and wherein the polymer is injected as a water solution at coacervate concentration in the substantial absence of additional water. A kit containing the injectable bioelastic polymer and a syringe is also provided.

Injectable implants for tissue augmentation and restoration

A method for tissue augmentation in a mammal is provided having injecting a polymer at a tissue site in need of augmentation and having a tissue temperature, the polymer having repeating peptide monomeric units selected from the group consisting of nonapeptide, pentapeptide and tetrapeptide monomeric units, wherein the monomeric units form a series of &bgr;-turns separated by dynamic bridging segments suspended between the &bgr;-turns, wherein the polymer has an inverse temperature transition T less than the tissue temperature, and wherein the polymer is injected as a water solution at coacervate concentration in the substantial absence of additional water. A kit containing the injectable bioelastic polymer and a syringe is also provided.

A drug delivery composition, comprising a bioelastic polymer, comprising monomeric units selected from the group consisting of bioelastic pentapeptides, tetrapeptides, and nonapeptides, and a drug retained by the polymer, wherein the polymer is selected to be in a first contraction state, selected from the group consisting of contracted and relaxed bioelastomer states, when contacted with a physiological condition present in a human or animal to whom the composition is administered and wherein the polymer contains a reactive functional group that undergoes a reaction, either in the presence of the physiological condition or when the polymer is transported by a natural process in the human or animal to a different location having a different physiological condition, to produce a second functional group, wherein the presence of the second functional group in the polymer causes the polymer to switch to the other of the contraction states, thereby making the drug available for release from the composition.

Bioelastomeric drug delivery system

A method for overexpressing a bioelastic polypeptide in a host cell is provided. A nucleic acid encoding a bioelastic polypeptide having pentapeptide, tetrapeptide, hexapeptide or nonapeptide repeating units is introduced into a host cell. The host cell is grown under conditions that provide for expression of the polypeptide as at least 40% of the total cellular protein of the host cell.

Hyperexpression of bioelastic polypeptides

The invention provides a method for improving the texture of a food product by incorporating in the food product or a precursor of the food product a bioelastic polypeptide in an amount sufficient to increase the elasticity of the food product, the bioelastic polypeptide having tetrapeptide or pentapeptide repeating units or mixtures thereof and the repeating units existing in a conformation having a .beta.-turn. The invention also provides a method for binding a food product precursor by adding a bioelastic polypeptide in an amount sufficient to bind the food product precursor, the bioelastomer having tetrapeptide or pentapeptide repeating units or mixtures thereof and the repeating units existing in a conformation having a .beta.-turn. The present invention further provides a food adjunct containing a bioelastic polypeptide having tetrapeptide or pentapeptide repeating units or mixtures thereof where the repeating units exist in a conformation having a .beta.-turn, and an edible material suitable for human or animal consumption.

Bioelastomers suitable as food product additives

A composition that expands or contracts upon a change in exposure to electrical energy is provided that comprises a protein or protein-based polymeric material having an inverse temperature transition in the range of liquid water, wherein at least a fraction of the monomers in the polymer contain an electrical energy-responsive group that undergoes a change in hydrophobicity or polarity upon a change in exposure to electrical energy and is present in an amount sufficient to provide a shift in the inverse temperature transition of the polymer upon the change in exposure to electrical energy. Compositions of the invention, including those further containing a side-chain chemical couple, can be used in a variety of different applications to produce mechanical work, cause turbidity changes, cause chemical changes in an enclosed environment, or transduce other free energies by varying the exposure to electrical energy on the composition. The degree and efficiency of mechanical or chemical change can be controlled by, inter alia, selection of the type, amount, position, and mole fraction of the electrical energy-responsive side chain group and hydrophobic residues in the polymer.

Polymers responsive to electrical energy

A method for purifying an artificial polymer that exhibits a reversible inverse temperature transition is provided. The method involves (a) dissolving the polymer in an aqueous medium so that the temperature of the medium is below the effective transition temperature; (b) adjusting the temperature of the aqueous medium relative to the effective transition temperature of the polymer; (c) removing any particulate material from the medium; (d) adjusting the temperature of the aqueous medium relative to the effective transition temperature of the polymer so that the temperature of the medium is above the effective transition temperature; (e) collecting the polymer from the medium as a more dense phase; and (f) optionally repeating any of steps (a)-(e) until a desired level or purity is reached; with the proviso the order of steps can be (a)-(d)-(e)-(a)-(b)-(c).

Simple method for the purification of a bioelastic polymer

The invention provides a bioelastomer comprising tetrapeptide and/or pentapeptide monomeric units of the formula:

Elastomeric polypeptide matrices for preventing adhesion of biological

Polymeric materials having an inverse temperature transition, particularly bioelastic polymers comprising monomeric units selected from the group consisting of bioelastic pentapeptides, tetrapeptides, and nonapeptides, have been found to have controllable absorbent properties that can be varied with temperature or contact with liquids. The materials are selected to be in a contracted or swollen state initially, depending on the specific use. When the material is located under different conditions (such as a different temperature resulting from being either in contact with or at distance from human skin), the material undergoes swelling or contraction to switch to the other state.

Superabsorbent materials and uses thereof

A vascular prosthetic material having at least one layer containing an elastomeric material capable of reversibly contracting and relaxing by an inverse temperature transition. The vascular prosthetic material matches the compliance and elasticity of vessels replaced, and is biocompatible and biodegradable. The material may also have incorporated therein chemotactic peptides and cell attachment sequences.

Elastomeric polypeptides as vascular prosthetic materials

The invention relates to a mechanochemical engine capable of converting chemical work to mechanical work. The mechanochemical engine comprises an elastomeric material capable of reversibly contracting and relaxing by an inverse temperature transition induced by changes in the chemical potential of a surrounding medium. Examples of elastomeric materials and their elastomeric units that may be used in the mechanochemical engine are described.

Growing community of inventors

Birmingham, AL, United States of America

Dan W Urry