Nanoscale platinum compounds and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2016367682-A1
Application number	US-201615182967-A
Country	US
Kind code	A1
Filing date	Jun 15, 2016
Priority date	Feb 4, 2009
Publication date	Dec 22, 2016
Grant date	—

Abstract

The invention is directed to biocompatible conjugated polymer nanoparticles including a copolymer backbone, a plurality of sidechains covalently linked to said backbone, and a plurality of platinum compounds dissociably linked to said backbone. The invention is also directed to dicarbonyl-lipid compounds wherein a platinum compound is dissociably linked to the dicarbonyl compound. The invention is also directed to methods of treating cancer or metastasis. The methods includes selecting a subject in need of treatment for cancer or metastasis and administering to the subject an effective amount of any of the nanoparticles, compounds, or compositions of the invention.

First claim

What is claimed:

1 . A biocompatible conjugated polymer nanoparticle comprising:
a copolymer backbone; a plurality of sidechains covalently linked to said backbone; and a plurality of platinum compounds dissociably linked to said backbone.

2 . The nanoparticle of claim 1 , wherein said plurality of platinum compounds is selected from Pt(II) compounds, Pt(IV) compounds, and any combinations thereof.

3 . The nanoparticle of claim 1 , wherein said copolymer comprises maleic acid monomers.

4 . The nanoparticle of claim 1 , wherein said sidechains are selected from the group consisting of polymers, monosaccharides, dicarboxylic acids, polyethylene glycol (PEG), and combinations thereof.

5 . The nanoparticle of claim 1 , wherein said platinum compound is a Pt(II) compound selected from the group consisting of cisplatin, oxaliplatin, carboplatin, paraplatin, sartraplatin, and combinations thereof.

6 . The nanoparticle of claim 1 , wherein at least one of said plurality of platinum compounds is linked to the backbone by at least one coordination bond, wherein the coordination bond is between an oxygen of the backbone and the platinum atom of the platinum compound.

7 . The biocompatible conjugated polymer nanoparticle of claim 1 , wherein said copolymer is poly(isobutylene-alt-maleic acid) comprising 25 to 50 monomer units; wherein said plurality of sidechains covalently linked to said backbone are PEG having a molecular weight of from 1000 to 3000 Dalton and wherein the number of said PEG sidechains corresponds to between 50% and 100% of the number of monomeric units of said polymer backbone; and wherein the number of said cisplatin sidegroups is between 25% and 75% of the number of monomeric units of said polymer backbone.

8 . The biocompatible conjugated polymer nanoparticle of claim 1 , wherein said copolymer is poly(isobutylene-alt-maleic acid) comprising from 25 to 50 monomers; wherein said plurality of sidechains covalently linked to said backbone are glucosamine; and wherein the number of said glucosamine sidechains is between 50% and 100% of monomeric units of said polymer backbone; and wherein the number of said cisplatin sidegroups is between 25% and 75% of the number of monomeric units of said polymer backbone.

9 . A carboxylic acid-platinum compound complex conjugated nanoparticle comprising:
a carboxylic acid-platinum compound complex; and a plurality of lipid-polymer chains, wherein the carboxylic acid portion of said carboxylic acid-platinum compound complex is covalently bound to said lipid-polymer chains.

10 . The nanoparticle of claim 9 , wherein the carboxylic acid is maleic acid.

11 . The nanoparticle of claim 9 , wherein the polymer is PEG.

12 . The nanoparticle of claim 9 , wherein the platinum compound is a Pt(II) compound selected from the group consisting of cisplatin, oxaliplatin, carboplatin, paraplatin, sartraplatin, and combinations thereof.

13 . The nanoparticle of claim 9 , wherein the platinum compound loading is from 1%-30%.

14 . A dicarbonyl-lipid compound having the structure

15 . A vesicle, micelle, liposome or nanoparticle compound comprising a dicarbonyl-lipid compound of claim 14 and a platinum compound, wherein the platinum compound is dissociably linked to the compound of claim 14 .

16 . The nanoparticle of claim 15 , wherein the platinum compound is selected from Pt(II) compounds, Pt(IV) compounds, and any combinations thereof.

17 . The nanoparticle of claim 16 , wherein said platinum compound is a Pt(II) compound selected from the group consisting of cisplatin, oxaliplatin, carboplatin, paraplatin, sartraplatin, and combinations thereof.

18 . A nanoparticle compound comprising a biocompatible polymer, wherein the polymer comprises at least one monomer having the formula —CH(CO 2 H)—R—CH(C(O)R′)—, wherein R is a bond or a C 1 -C 6 alkylene, where the alkylene can comprise one or more double or triple bonds; and R′ is a substituted nitrogen atom.

19 . The nanoparticle of claim 18 , wherein R′ is

or —NH(CH 2 CH 2 O) m CH 3 , wherein m is 1-150.

20 . The nanoparticle of claim 18 , further comprising a bioactive agent.

21 . A biocompatible polymer comprising:
a copolymer backbone; a plurality of sidechains covalently linked to the backbone; and a plurality of platinum compounds dissociably linked to the backbone, wherein at least one of said plurality of platinum compounds is linked to said backbone through at least one coordination bond and said coordination bond is between an oxygen of the backbone and the platinum atom of the platinum compound.

22 . The biocompatible polymer of claim 21 , wherein said oxygen is a carbonyl oxygen or an amide oxygen.

23 . The biocompatible polymer of claim 21 , wherein said plurality of platinum compounds is selected from Pt(II) compounds, Pt(IV) compounds, and any combinations thereof.

24 . The biocompatible polymer of claim 23 , wherein said platinum compound is a Pt(II) compound selected from the group consisting of cisplatin, oxaliplatin, carboplatin, paraplatin, sartraplatin, and combinations thereof.

25 . The biocompatible polymer of claim 21 , wherein the copolymer backbone comprises from 2 to 100 monomer units.

26 . The biocompatible polymer of claim 21 , wherein the copolymer backbone is poly(isobutylene-alt-maleic acid) (PIMA).

27 . The biocompatible polymer of claim 21 , wherein the copolymer backbone comprises at least one monomer having the formula —CH(CO 2 H)—R—CH(C(O)R′)—, —CH(CO 2 H)—R—CH(C(O)R′)CH 2 C(Me 2 )-, or —CH(C(O)R′)—R—CH(CO 2 H)—CH 2 C(Me 2 )- wherein R is a bond, C 1 -C 6 alkylene, where the alkylene can comprise one or more double or triple bonds; and R′ is a substituted nitrogen atom.

28 . The biocompatible polymer of claim 21 , wherein said sidechains are selected from the group consisting of polymers, monosaccharides, dicarboxylic acids, and combinations thereof.

29 . The biocompatible polymer of claim 21 , wherein the number of sidechains corresponds between 50% and 100% of the number of monomeric units of said polymer backbone.

30 . The biocompatible polymer of claim 21 , wherein the number of said platinum compounds corresponds between 10% and 100% of the number of monomeric units of said polymer backbone.

31 . The biocompatible polymer of claim 21 , wherein the biocompatible polymer comprises:
a poly(isobutylene-alt-maleic acid) backbone, wherein said backbone contains 25 to 50 monomer units; a plurality of PEG sidechains or glucosamine sidechains covalently linked to said backbone, wherein said PEG sidechains have a molecular weight of from 1000 to 3000 Dalton and wherein the number of said PEG sidechains or glucosamine side chains corresponds to between 50% and 100% of the number of monomeric units of said polymer backbone; and a plurality of cisplatin sidegroups dissociably linked to said backbone wherein the number of said cisplatin sidegroups is between 25% and 75% of the number of monomeric units of said polymer backbone.

32 . The biocompatible polymer of claim 21 , wherein the biocompatible

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Sengupta Shiladitya
• Paraskar Abhimanyu
• Soni Shivani
• Basu Sudipta
• Sengupta Poulomi

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title