IP Library Granted Patent US 9,557,337
Granted Patent B2
US 9,557,337 · App. 14/501,811 · Granted Jan 31, 2017

Polymersome encapsulation of hydrophobic fluorescent polymers

Inventors: Majid Mehrpouyan (Gilroy, CA); Shumeye Mamo (San Ramon, CA); Marybeth Sharkey (San Jose, CA)
Assignee: Becton, Dickinson and Company
G01N33/582C09K11/025C09K11/06C09K2211/14
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Quick Facts
Patent No.
US 9,557,337
App. No.
14/501,811
Granted
Jan 31, 2017
Kind
B2
Abstract

Described herein are aqueous soluble polymersomes that encapsulate one or more hydrophobic fluorescent polymers and methods of their preparation and use.

Claims (41)

1. An aqueous soluble polymersome comprising:

(a) one or more hydrophobic fluorescent polymers; and

(b) a plurality of amphiphilic diblock copolymers encapsulating the one or more hydrophobic fluorescent polymers, the copolymers each comprising a hydrophobic block that forms a hydrophobic core structure and a hydrophilic block on the surface of the polymersome that is oriented toward an aqueous phase;

wherein the hydrophobic block is selected from poly(lactide-co-glycolic acid) (PLGA), polvlactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), poly(methyl methacylate) (PMMA), polydimethylsiloxane (PDMS), polyethylene (PE) and polystyrene (PS); and

the hydrophilic block is selected from a hydrophilic polysaccharide, a polyether, polymethacrylate, poly(methacrylic acid), polyacrylic acid, polyacrylate, poly(alkylacrylic acid), poly(alkylacrylate), polyacrylamide, poly(N-isopropylacrylamide), poly(2-ethyl-2-oxazoline), poly(vinyl alcohol), poly(vinyl acid), poly(2-methyloxazoline) and copolymer combinations thereof.

2. The aqueous soluble polymersome of claim 1 wherein the hydrophobic block is selected from poly(lactide-co-glycolic acid) (PLGA), polylactide (PLA), polyglycolide (PGA), and polycaprolactone (PCL).

3. The aqueous soluble polymersome of claim 1 , wherein the hydrophobic block is poly(lactide-co-glycolic acid) (PLGA).

4. The aqueous soluble polymersome of claim 3 , wherein the polymer ratio of PLGA is 50:50 (DL-lactide:glycolide).

5. The aqueous soluble polymersome of claim 1 , wherein the hydrophobic block has a number average molecular weight of about 2,000 to 20,000 Daltons.

6. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block is selected from a hydrophilic polysaccharide and a polyoxyalkylene.

7. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block is polypropylene glycol (PPG), dextrin, amylopectin or polyethylene glycol (PEG).

8. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block is poly(2-methyloxazoline).

9. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block has a number average molecular weight of about 1,000 to about 10,000 Daltons.

10. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block further comprises an amine moiety.

11. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block is attached to a biosensor molecule.

12. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block is attached to a signaling chromophore for resonant energy transfer.

13. The aqueous soluble polymersome of claim 1 , wherein the hydrophilic block is attached to an antigen-specific antibody.

14. The aqueous soluble polymersome of claim 1 , wherein the hydrophobic block is PLGA and the hydrophilic block is PEG.

15. The aqueous soluble polymersome of claim 14 , wherein the PLGA has a number average molecular weight of about 5,000 Daltons and the PEG has a number average molecular weight of about 2,000 Daltons.

16. The aqueous soluble polymersome of claim 1 , wherein the one or more hydrophobic fluorescent polymers are polyfluorene polymer, polyfluorene copolymer, or fluorescent homopolymer.

17. The aqueous soluble polymersome of claim 1 , wherein the one or more hydrophobic fluorescent polymers are selected from poly[(9,9-dioctyl-2,7-divinylenefluorenylene)-alt-co-(9,10-anthracene)]; poly[(9,9-dioctyl-2,7-divinylenefluorenylene)-alt-co-{2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene}]; poly[(9,9-dioctyl-2,7-divinylenefluorenylene)-alt-co-(1,4-phenylene)]; poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-{2,1′,3}-thiadiazole)]; poly[(9,9-dihexylfluorenyl-2,7-diyl)-alt-co-(2-methoxy-5-{2-ethylhexyloxy}-1,4-phenylene)]; poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(2,5-p-xylene)]; poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(N,N′-diphenyl)-N,N′-di(p-butylphenyl)-1,4-diamino-benzene)]; poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1′,3}-thiadiazole)]; poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene-vinylene], optionally end capped with dimethylphenyl; poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylene-vinylene], optionally end capped with polysilsesquioxane; poly[2-methoxy-5-(3,7-dimethyloctyloxy)-1,4-phenylene-vinylene], optionally end capped with dimethylphenyl; poly[2-methoxy-5-(3,7-dimethyloctyloxy)-1,4-phenylene-vinylene], optionally end capped with polysilsesquioxane; poly[9,9-dioctylfluorenyl-2,7-diyl], optionally end capped with dimethylphenyl; poly[9,9-dioctylfluorenyl-2,7-diyl], optionally end capped with polysilsesquioxane; poly[9,9-dioctylfluorenyl-2,7-diyl], optionally end capped with N,N-bis(4-methylphenyl)-aniline; poly[9,9-dioctylfluorenyl-2,7-diyl], optionally end capped with 2,5-diphenyl-1,2,4-oxadiazole; poly[9,9-di-(2-ethylhexyl)-fluorenyl-2,7-diyl], optionally end capped with dimethylphenyl; poly[9,9-di-(2-ethylhexyl)-fluorenyl-2,7-diyl], optionally end capped with polysilsesquioxane; poly[9,9-di-(2-ethylhexyl)-fluorenyl-2,7-diyl], optionally end capped with N,N-bis(4-methylphenyl)-aniline; poly[9,9-di-(2-ethylhexyl)-fluorenyl-2,7-diyl], optionally end capped with 2,5-diphenyl-1,2,4-oxadiazole; poly[2-(5-cyano-5-methylhexyloxy)-1,4-phenylene], optionally end capped with dimethylphenyl; and poly[2,5-dioctyl-1,4-phenylene], optionally end capped with dimethylphenyl; poly[9,9-di(3,3′-N,N′-trimethyl-ammonium)propylfluorenyl-2,7-diyl]-alt-(9,9-dioctylfluorenyl-2,7-diyl)] diiodide salt, optionally end capped with dimethylphenyl; poly[2,5-bis(3,7-dimethyloctyloxy)-1,4-phenylene-vinylene]; poly(9,9-di{2-[2-(2-methoxy-ethoxy)ethoxy]ethyl}fluorenyl-2,7-diyl), optionally end capped with dimethylphenyl; and poly-BODIPY fluorescent polymers.

18. The aqueous soluble polymersome of claim 1 , wherein the polymersome comprises at least two hydrophobic fluorescent polymers.

19. An aqueous soluble polymersome comprising:

(a) one or more hydrophobic fluorescent polymers;

(b) a plurality of amphiphilic diblock copolymers encapsulating the one or more hydrophobic fluorescent polymers, the copolymers each comprising a hydrophobic block that forms a hydrophobic core structure and a hydrophilic block on the surface of the polymersome that is oriented toward an aqueous phase, wherein:

the hydrophobic block is selected from poly(lactide-co-glycolic acid) (PLGA), polvlactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), poly(methyl methacylate) (PMMA), polydimethylsiloxane (PDMS), polyethylene (PE) and polystyrene (PS); and

the hydrophilic block is selected from a hydrophilic polysaccharide, a polyether, polymethacrylate, poly(methacrylic acid), polyacrylic acid, polyacrylate, poly(alkylacrylic acid), poly(alkylacrylate), polyacrylamide, poly(N-isopropylacrylamide), poly(2-ethyl-2-oxazoline), poly(vinyl alcohol), poly(vinyl acid), poly(2-methyloxazoline) and copolymer combinations thereof; and

(c) an acceptor dye.

20. The polymersome of claim 19 , wherein:

the hydrophobic block is selected from poly(lactide-co-glycolic acid) (PLGA), polvlactide (PLA), polyglycolide (PGA) and polycaprolactone (PCL); and

the hydrophilic block is selected from polypropylene glycol (PPG), dextrin, amylopectin and polyethylene glycol (PEG).

21. An aqueous soluble polymersome comprising:

(a) one or more hydrophobic fluorescent polymers;

(b) a plurality of amphiphilic diblock copolymers encapsulating the one or more hydrophobic fluorescent polymers, the copolymers each comprising a hydrophobic block that forms a hydrophobic core structure and a hydrophilic block on the surface of the polymersome that is oriented toward an aqueous phase, wherein the hydrophobic block is selected from poly(lactide-co-glycolic acid) (PLGA), polvlactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), poly(methyl methacylate) (PMMA), polydimethylsiloxane (PDMS), polyethylene (PE) and polystyrene (PS); and the hydrophilic block is selected from a hydrophilic polysaccharide, a polyether, polymethacrylate, poly(methacrylic acid), polyacrylic acid, polyacrylate, poly(alkylacrylic acid), poly(alkylacrylate), polyacrylamide, poly(N-isopropylacrylamide), poly(2-ethyl-2-oxazoline), poly(vinyl alcohol), poly(vinyl acid), poly(2-methyloxazoline) and copolymer combinations thereof;

(c) an acceptor dye; and

(d) one or more antioxidants.

22. The polymersome of claim 21 , wherein:

the hydrophobic block is selected from poly(lactide-co-glycolic acid) (PLGA), polvlactide (PLA), polyglycolide (PGA) and polycaprolactone (PCL); and

the hydrophilic block is selected from polypropylene glycol (PPG), dextrin, amylopectin and polyethylene glycol (PEG).

23. The polymersome of claim 19 , wherein the hydrophobic block is PLGA and the hydrophilic block is PEG.

24. The polymersome of claim 21 , wherein the hydrophobic block is PLGA and the hydrophilic block is PEG.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 4, 2014
From: MEHRPOUYAN, MAJID; MAMO, SHUMEYE; SHARKEY, MARYBETH
To: BECTON, DICKINSON AND COMPANY
Reel/Frame 034099/0235 →
Continuity (2)
Provisional Application 61885932 · Oct 2, 2013
Related Publication 20150140549A1 · May 21, 2015