Telodendrimers with enhanced drug delivery

Patent metadata

Field	Value
Publication number	US-10406233-B2
Application number	US-201214365929-A
Country	US
Kind code	B2
Filing date	Dec 19, 2012
Priority date	Dec 21, 2011
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

The present invention provides amphiphilic telodendrimers that aggregate to form nanocarriers characterized by a hydrophobic core and a hydrophilic exterior. The nanocarrier core may include amphiphilic functionality such as cholic acid or cholic acid derivatives, and the exterior may include branched or linear poly(ethylene glycol) segments. Nanocarrier cargo such as hydrophobic drugs and other materials may be sequester in the core via non-covalent means or may be covalently bound to the telodendrimer building blocks. Telodendrimer structure may be tailored to alter loading properties, interactions with materials such as biological membranes, and other characteristics.

First claim

What is claimed is:

1. A compound selected from the group consisting of:

wherein
each branched monomer unit X is lysine;
L is a bond;
PEG is a polyethyleneglycol (PEG) polymer, having a molecular weight of 1-100 kDa;
R′ is selected from the group consisting of cholic acid (CA), (3α, 5β, 7α, 12α)-7,12-dihydroxy-3-(2,3-dihydroxy-1-propoxy)-cholic acid (CA-4OH), (3α, 5β, 7α, 12α)-7-hydroxy-3,12-di(2,3-dihydroxy-1-propoxy)-cholic acid (CA-5OH), (3α, 5β, 7α, 12α)-7,12-dihydroxy-3-(3-amino-2-hydroxy-1-propoxy)-cholic acid (CA-3OH—NH 2 ); and
R″ is selected from the group consisting of cholesterol formate (CF), doxorubicin (DOX), and rhein (Rh).

2. The compound of claim 1 , wherein the compound has the formula:

wherein
each X is lysine;
PEG is PEG5k; and
each R′ is CA-4OH, or
each R′ is CA-5OH, or
each R′ is CA-3OH—NH 2 .

3. The compound of claim 1 , wherein the compound has the formula:

wherein
each X is lysine having an α amino and an ε amino, wherein each R′ is linked to the α amino and each R″ is linked to the ε amino;
PEG is PEG5k; and
each R′ is CA, and each R″ is CF, or
each R′ is CA, and each R″ is Rh.

4. A nanocarrier having an interior and an exterior, the nanocarrier comprising a plurality of compounds of claim 1 , wherein each compound self-assembles in an aqueous solvent to form the nanocarrier such that a hydrophobic pocket is formed in the interior of the nanocarrier, and wherein the PEG of each compound self-assembles on the exterior of the nanocarrier.

5. A method of treating a disease, comprising administering to a subject in need of such treatment, a therapeutically effective amount of a nanocarrier of claim 4 , wherein the nanocarrier further comprises a drug.

6. A method of imaging, comprising administering to a subject to be imaged, an effective amount of a nanocarrier of claim 4 , wherein the nanocarrier further comprises an imaging agent.

Assignees

• Univ California

Inventors

• Luo Juntao
• Lam Kit

Classifications

• C08G83/004 Primary

  After treatment of dendrimers · CPC title

• C08G65/33396

  having oxygen in addition to nitrogen · CPC title

• C08G65/33303

  containing amino group · CPC title

• A61K47/595

  Polyamides, e.g. nylon (polyamino acids A61K47/62) · CPC title

• A61K47/645

  Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT · CPC title