Triggered release from proteinoid microspheres
View Patent ↗The invention provides proteinoid microsphere made up of a mixture of thermally condensed amino acids that are crosslinked with a bis dithiol crosslinker reagent. The proteinoid microspheres of the invention may be used to encapsulate a material or a compound and to provide slow, sustained or timed release of the material or compound. The proteinoid microspheres are stable in solution until exposed to a reducing agent. However, the in vivo environment provides a sufficient reduction potential to provide slow, sustained release of materials contained therein from the proteinoid microspheres of the present invention.
1. A method of releasing a therapeutic agent from a proteinoid microsphere comprising introducing a therapeutic agent encapsulated with a proteinoid microsphere comprising a mixture of amino acids that are thermally condensed and crosslinked with a crosslinker of any one of the formulae I-VI into a reducing environment:
COOH—S—S—(CH2) n —S—S—COOH I
COOH—S—S—X—S—S—COOH II
NH2—S—S—(CH2) n —S—S—NH2 III
NH2—S—S—X—S—S—NH2 IV
Aryl—S—S—(CH2) n —S—S—Aryl V
Aryl—S—S—X—S—S—Aryl VI
wherein:
X is a spacer group of about 3 to 100 angstroms by about 2 to 30 angstroms that comprises an alkane chain, an alkene chain, a cycloalkyl or aryl ring having five to fourteen carbon atoms, or a combination thereof;
n is an integer ranging from 1 to 18;
S is a sulfur atom; and
Aryl is a phenyl radical or an ortho-fused bicyclic radical having about nine to ten ring atoms wherein at least one ring is aromatic and wherein each Aryl moiety is substituted with at least one reactive group that can form a covalent linkage with an amino acid.
2. The method of claim 1 wherein the reactive group that can form a covalent linkage with an amino acid is carboxylate, nitro, amino or sulfhydryl.
3. The method of claim 1 wherein the reactive group that can form a covalent linkage with an amino acid is a carboxylate group.
4. The method of claim 1 wherein the therapeutic agent is released from the proteinoid microsphere into a wound.
5. The method of claim 4 wherein the wound is a chronic wound.
6. The method of claim 1 wherein the therapeutic agent is released from the proteinoid microsphere into the bloodstream of a mammal.
7. The method of claim 1 wherein the therapeutic agent is released from the proteinoid microsphere into the digestive track of a mammal.
8. The method of claim 1 wherein the reducing environment is serum.
9. A method of releasing a therapeutic agent from a proteinoid microsphere comprising introducing a therapeutic agent encapsulated with a proteinoid microsphere comprising a mixture of amino acids that are thermally condensed and crosslinked with a crosslinker reagent of formula VII into a reducing environment:
10. The method of claim 9 wherein the therapeutic agent is released from the proteinoid microsphere into a wound.
11. The method of claim 10 wherein the wound is a chronic wound.
12. A method of sustained release of a therapeutic agent into the bloodstream of a mammal comprising administering a therapeutic agent encapsulated within a proteinoid microsphere to the bloodstream of a mammal mammal, wherein the proteinoid microsphere comprises a mixture of amino acids that are thermally condensed and crosslinked with a crosslinker of any one of the formulae I–VI:
COOH—S—S—(CH2) n —S—S—COOH I
COOH—S—S—X—S—S—COOH II
NH2—S—S—(CH2) n —S—S—NH2 III
NH2—S—S—X—S—S—NH2 IV
Aryl—S—S—(CH2) n —S—S—Aryl V
Aryl—S—S—X—S—S—Aryl VI
wherein:
X is a spacer group of about 3 to 100 angstroms by about 2 to 30 angstroms that comprises an alkane chain, an alkene chain, a cycloalkyl or aryl ring having five to fourteen carbon atoms, or a combination thereof;
n is an integer ranging from 1 to 18;
S is a sulfur atom; and
Aryl is a phenyl radical or an ortho-fused bicyclic radical having about nine to ten ring atoms wherein at least one ring is aromatic and wherein each Aryl moiety is substituted with at least one reactive group that can form a covalent linkage with an amino acid.
13. The method of claim 12 wherein the reactive group that can form a covalent linkage with an amino acid is carboxylate, nitro, amino or sulfhydryl.
14. The method of claim 12 wherein the reactive group that can form a covalent linkage with an amino acid is a carboxylate group.
15. A method of sustained release of a therapeutic agent into the bloodstream of a mammal comprising administering a therapeutic agent encapsulated with a proteinoid microsphere to the bloodstream of a mammal, wherein the proteinoid microsphere comprises a mixture of amino acids that are thermally condensed and crosslinked with a crosslinker reagent of formula VII: