Carrier nanoparticles and related compositions, methods and systems

Patent metadata

Field	Value
Publication number	US-10155051-B2
Application number	US-201815885944-A
Country	US
Kind code	B2
Filing date	Feb 1, 2018
Priority date	Aug 13, 2008
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

Carrier nanoparticles comprising a polymer containing a polyol coupled to a polymer containing a boronic acid and a linkage cleavable under reducing conditions, configured to present the polymer containing a boronic acid to an environment external to the nanoparticle and related compositions, methods and systems.

First claim

What is claimed is:

1. A method of delivering a therapeutic agent to a human patient, to treat a functional disorder in a human patient's body, the method comprising administering to the human patient a plurality of nanoparticles having a targeting ligand and a therapeutic agent effective for treating the functional disorder, wherein
each nanoparticle comprises a polymer containing a polyol and a polymer containing a phenylboronic acid,
wherein the polymer containing the phenylboronic acid is conjugated to the polymer containing the polyol with a reversible borate ester linkage;
wherein the nanoparticle is configured to present the polymer containing a phenylboronic acid to an environment external to the nanoparticle;
wherein the polymer containing a polyol comprises one or more of at least one of the following structural units of Formula (I), (II), or (II):

wherein A is independently derived from

 and
wherein B is derived from:

in which
q is 1-20;
p is 20-200; and
L is a leaving group; and

wherein the polymer containing a phenylboronic acid comprises at least one terminal phenylboronic acid group and has the general formula:

wherein
R 3 and R 4 are independently (CH 2 CH 2 O) t , where t is from 2 to 2000,
X 1 is —NH—C(═O)—, —S—S—, —C(═O)—NH—, —O—C(═O)— or —C(═O)—O—,
Y 1 is a phenyl group,
wherein r=1, a=0 and b=1, and
wherein Functional group 1 and Functional group 2 are the same or different and independently comprise —B(OH) 2 , —OCH 3 , —(X 1 )—(Y 1 )—B(OH) 2 , —COOH, —NH 2 , or —OH.

2. The nanoparticle of claim 1 , wherein the structural unit of formula (I) is:

3. The nanoparticle of claim 1 , wherein the structural unit of formula (II) is:

4. The nanoparticle of claim 1 , wherein the structural unit of formula (III) is:

in which
n is 1-20.

5. The nanoparticle of claim 1 , wherein the polymer containing the polyol has a repeating unit of:

6. The nanoparticle of claim 2 , wherein functional group 1 and functional group 2 are the same or different and are independently selected from —B(OH) 2 , —OCH 3 , —OH.

7. The nanoparticle of claim 2 , wherein the polymer containing a phenylboronic acid is:

wherein t is a number from 200 to 300.

8. The method of claim 1 , wherein the functional disorder is a mental disorder.

9. The method of claim 1 , wherein the functional disorder is a physical disorder.

10. The method of claim 1 , wherein the therapeutic agent is a chemotherapeutic agent.

11. The method of claim 10 , wherein the chemotherapeutic agent is an epothilone, a camptothecin-based drug, taxol, or a nucleic acid, or a combination thereof.

12. The method of claim 10 , wherein the chemotherapeutic is camptothecin, an epothilone, a taxane or a combination thereof.

13. The method of claim 11 , wherein the nucleic acid is a plasmid, siRNA, shRNA, miRNA, antisense oligonucleotide, aptamer, or a combination thereof.

14. The method of claim 1 , wherein the targeting ligand is a vitamin, a protein, a monosaccharide, a peptide, a peptide aptamer, an oligopeptide, a polypeptide or fragment thereof, a polysaccharide, a polynucleotide, an antibody, or an antibody fragment.

15. The method of claim 1 , wherein the targeting ligand is transferrin, folic acid, or galactose.

16. The method of claim 14 , wherein the polynucleotide is interfering RNA.

17. The method of claim 1 , wherein the targeting ligand is a ligand for a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein.

18. The method of claim 1 , wherein the functional disorder is a mental or physical disorder, and the targeting ligand is a cellular receptor, a cellular receptor protein, a ligand for a cellular receptor, or cellular receptor protein.

Assignees

• California Inst Of Techn

Inventors

• Davis Mark E
• Alabi Akinleye

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title