Nanoparticulate drug delivery systems
AssigneeDuke University
InventorsParisa Yousefpour, Ashutosh Chilkoti
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Abstract
Described herein are compositions that include an assembly of self-assembling conjugates. The self-assembling conjugates may include a polypeptide having a transition temperature (17) above 50° C. when the polypeptide is not attached to the conjugate, an albumin binding domain (ABD) attached to a first end of the polypeptide, and at least one molecule attached to a second end of the polypeptide through a cysteine group, wherein the molecule has an octanol-water distribution coefficient (log D) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate. Also described herein are methods of using the compositions.
Claims16
A composition comprising:
- an assembly of self-assembling conjugates, each self-assembling conjugate comprising
- a polypeptide having a transition temperature (Tt) above 50° C. when the polypeptide is not attached to the conjugate, wherein the polypeptide comprises an amino acid sequence of (X1GVPG)m (SEQ ID NO:
- 3), wherein X1 is A or V:
- A:
- G at a ratio of 1:7:8 and m is 160 and wherein the polypeptide comprises an amino acid sequence of (CGG), (SEQ ID NO:4) at its C-terminus, wherein z is 1 to 40;
- an albumin binding domain (ABD) attached to a first end of the polypeptide's N-terminus, wherein the ABD comprises an amino acid sequence of SEQ ID NO:
- 6;
- and
- at least one molecule attached to a thiol group of an individual cysteine of SEQ ID NO:4 through a linker, wherein the molecule is a chemotherapeutic or an imaging agent, and wherein the molecule has an octanol-water distribution coefficient (logD) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate,
- wherein the conjugate has a Tt above 40° C. at a concentration of 100 uM.
A composition comprising:
- an assembly of self-assembling conjugates, each self-assembling conjugate comprising
- a polypeptide having a transition temperature (Tt) above 50° C. when the polypeptide is not attached to the conjugate, wherein the polypeptide comprises an amino acid sequence of (X1GVPG)m (SEQ ID NO:
- 3), wherein X1 is A or V:
- A:
- G at a ratio of 1:7:8 and m is 160 and wherein the polypeptide comprises an amino acid sequence of (CGG), (SEQ ID NO:4) at its C-terminus, wherein z is 1 to 40;
- an albumin binding domain (ABD) attached to the polypeptide's N-terminus, wherein the ABD attached to the polypeptide lowers the Tt of the polypeptide no more than 5° C. relative to the polypeptide's Tt when the polypeptide is not attached to the ABD or the conjugate, and wherein the ABD comprises an amino acid sequence of SEQ ID NO:6;
- and
- at least one molecule attached to a thiol group of an individual cysteine of SEQ ID NO:4 through a linker, wherein the molecule is a chemotherapeutic or an imaging agent, and wherein the molecule has an octanol-water distribution coefficient (logD) of greater than or equal to 1.5 at a pH of 7.4 when the molecule is not attached to the conjugate.
Dependencies are inferred from the claim text.