Methods and compositions related to synthetic nanocarriers with rapamycin in a stable, super-saturated state

Patent metadata

Field	Value
Publication number	US-2016128987-A1
Application number	US-201514934135-A
Country	US
Kind code	A1
Filing date	Nov 5, 2015
Priority date	Nov 5, 2014
Publication date	May 12, 2016
Grant date	—

Abstract

Disclosed are compositions and methods that provide synthetic nanocarriers that comprise hydrophobic polyester carrier material and rapamycin that is in a stable, super-saturated amount. In some embodiments, the synthetic nanocarriers are also initially sterile filterable. In other embodiments, the rapamycin is present in the synthetic nanocarrier compositions in an amount that is less than 50 weight % rapamycin/hydrophobic polyester carrier material in the composition.

First claim

1 . A composition comprising:
synthetic nanocarriers comprising a hydrophobic polyester carrier material and rapamycin; wherein the rapamycin is present in the synthetic nanocarriers in a stable, super-saturated amount that is less than 50 weight % rapamycin/hydrophobic polyester carrier material; and wherein the synthetic nanocarriers are initially sterile filterable.

2 . The composition of claim 1 , wherein the rapamycin is present in a stable, super-saturated amount that is less than 45 weight %.

3 - 10 . (canceled)

11 . The composition of claim 1 , wherein the hydrophobic polyester carrier material comprises PLA, PLG, PLGA or polycaprolactone.

12 . (canceled)

13 . The composition of claim 1 , wherein the amount of the hydrophobic polyester carrier material in the synthetic nanocarriers is 5-95 weight % hydrophobic polyester carrier material/total solids.

14 . (canceled)

15 . The composition of claim 1 , wherein the synthetic nanocarriers further comprise a non-ionic surfactant with HLB value less than or equal to 10.

16 . The composition of claim 1 , wherein the non-ionic surfactant with HLB value less than or equal to 10 comprises a sorbitan ester, fatty alcohol, fatty acid ester, ethoxylated fatty alcohol, poloxamer or a fatty acid.

17 - 18 . (canceled)

19 . The composition of claim 1 , wherein the non-ionic surfactant with HLB value less than or equal to 10 is encapsulated in the synthetic nanocarriers, present on the surface of the synthetic nanocarriers, or both.

20 . The composition of claim 1 , wherein the amount of non-ionic surfactant with HLB value less than or equal to 10 is ≧0.1 but ≦15 weight % non-ionic surfactant with a HLB value less than or equal to 10/weight hydrophobic polyester carrier material.

21 - 22 . (canceled)

23 . The composition of claim 1 , wherein the composition is initially sterile filterable through a 0.22 μm filter.

24 . The composition of claim 1 , wherein the mean of a particle size distribution obtained using dynamic light scattering of the synthetic nanocarriers is a diameter greater than 120 nm.

25 - 30 . (canceled)

31 . The composition of claim 1 , wherein the rapamycin is encapsulated in the synthetic nanocarriers.

32 . The composition of claim 1 , wherein the composition further comprises an antigen.

33 - 34 . (canceled)

35 . A kit comprising:
the composition of claim 1 for use in any one of the methods provided herein.

36 - 40 . (canceled)

41 . A method comprising administering the composition of claim 1 to a subject.

42 - 45 . (canceled)

46 . A method for producing synthetic nanocarriers comprising a hydrophobic polyester carrier material and rapamycin, comprising:
obtaining or providing the hydrophobic polyester carrier material, obtaining or providing rapamycin in an amount that exceeds the saturation limit of the rapamycin, combining the hydrophobic polyester carrier material and rapamycin, and stabilizing the rapamycin.

47 - 69 . (canceled)

Assignees

• Selecta Biosciences Inc

Inventors

• O'Neil Conlin
• Griset Aaron P
• Altreuter David H

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61K31/436 Primary

  the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin · CPC title

• A61K9/107

  Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)} · CPC title