Carrier for in vivo delivery of a therapeutic agent
AssigneesRutgers, The State University of New Jersey, University of Medicine and Dentistry of New Jersey
InventorsStanley Stein, Michael J. Leibowitz, Patrick J. Sinko
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Abstract
A carrier for in vivo delivery of a therapeutic agent comprising a thiol group is provided, wherein the therapeutic agent is conjugated to the carrier via a biodegradable disulfide bond. Since extracellular fluids in vivo do not provide the appropriate environment to efficiently reduce a disulfide bond, while cellular cytosol does provide an appropriate environment, the agent will remain substantially coupled to the carrier while circulating through the body until the carrier crosses a cell membrane. As a result, the therapeutic agent is protected from degradation and renal clearance, and the potential for the therapeutic agent to elicit an immune response is limited.
Claims71
A carrier for in-vivo delivery of a therapeutic agent comprising a thiol group, wherein said carrier comprises:
- a) a polymer selected from the group consisting of carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3-dioxolane, poly-1,3,6-trioxane, amino acid homopolymers, amino acid copolymers, polypropylene glycol, copolymers of ethylene glycol/propylene glycol, ethylene/maleic anhydride copolymer, copolymer of polyethylene glycol and an amino acid, polypropylene oxide/ethylene oxide copolymers, polyethylene glyco/thiomalic acid copolymers and unbranched polyethylene glycol;
- b) multiple thiol compounds each comprising a sulfur atom conjugated to said polymer such that said sulfur atom of said thiol compound and said thiol group of said therapeutic agent can form a disulfide bond.
A conjugate for in-vivo delivery of a therapeutic agent comprising a thiol group, wherein said conjugate comprises:
- a) a polymer selected from the group consisting of carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinyl pyrrolidone, poly-1,3-dioxolane, poly-1,3,6-trioxane, amino acid homopolymers, amino acid copolymers, polypropylene glycol, copolymers of ethylene glycol/propylene glycol, ethylene/maleic anhydride copolymer, copolymer of polyethylene glycol and an amino acid, polypropylene oxide/ethylene oxide copolymers, polyethylene glyco/thiomalic acid copolymers and unbranched polyethylene glycol;
- b) multiple thiol compounds each comprising a sulfur atom conjugated to said polymer such that said sulfur atom of said thiol compound and said thiol group of said therapeutic agent can form a disulfide bond;
- and
- c) a therapeutic agent comprising a thiol group bound to said polymer through said disulfide bond.
A carrier for in-vivo delivery of a therapeutic agent comprising a thiol group, wherein said carrier comprises:
- a) a polyaminoacid;
- b) multiple thiol compounds each comprising a sulfur atom conjugated to said polyaminoacid such that said sulfur atom of said thiol compound and said thiol group of said therapeutic agent can form a disulfide bond;
- and
- c) a cell uptake promoter conjugated to said polyaminoacid.
A conjugate for in-vivo delivery of a therapeutic agent comprising a thiol group, wherein said conjugate comprises:
- a) a polyaminoacid;
- b) multiple thiol compounds each comprising a sulfur atom conjugated to said polyaminoacid such that said sulfur atom of said thiol compound and said thiol group of said therapeutic agent can form a disulfide bond;
- and
- c) a therapeutic agent comprising a thiol group bound to said polymer through said disulfide bond, wherein said therapeutic agent comprising a thiol group, further comprises a cell uptake promoter conjugated thereto.
A method for intracellular delivery in a mammal of a therapeutic agent comprising a thiol group comprising administering to said mammal an intracellular delivery promoting amount of a conjugate comprising
- a) a polymer;
- b) multiple thiol compounds each comprising a sulfur atom conjugated to said polymer such that said sulfur atom of said thiol compound and said thiol group of said therapeutic agent can form a disulfide bond;
- and
- c) a therapeutic agent comprising a thiol group bound to said polymer through said disulfide bond, wherein said therapeutic agent comprising a thiol group, further comprises a cell uptake promoter conjugated thereto.
A method for intracellular delivery in a mammal of a therapeutic agent comprising a thiol group comprising administering to said mammal an intracellular delivery promoting amount of a conjugate comprising
- a) a polymer and a cell uptake promoter conjugated thereto;
- b) multiple thiol compounds each comprising a sulfur atom conjugated to said polymer such that said sulfur atom of said thiol compound and said thiol group of said therapeutic agent can form a disulfide bond;
- and
- c) a therapeutic agent comprising a thiol group bound to said polymer through said disulfide bond.
A method for increasing the intracellular uptake of a therapeutic agent comprising a thiol group comprising the steps of
- i) preparing a polymer comprising multiple thiol compounds to which said therapeutic agent is bound via a disulfide bond, said therapeutic agent or said polymer comprising a cell uptake promoter;
- ii) exposing cells to said polymer.
Dependencies are inferred from the claim text.