Controlled release formulations for the induction and proliferation of blood cells

Patent metadata

Field	Value
Publication number	US-2020405644-A1
Application number	US-202016942656-A
Country	US
Kind code	A1
Filing date	Jul 29, 2020
Priority date	Jan 24, 2012
Publication date	Dec 31, 2020
Grant date	—

Abstract

The absence of regulatory T cells (Treg) may underlie disorders including but not limited to autoimmunity, dermatitis, periodontitis and even transplant rejection. Enhancing local numbers of Treg through in situ Treg expansion or induction is contemplated herein as a treatment option for these disorders. Current methods for in vivo Treg expansion are not Treg specific and are associated with many adverse side-effects. The data presented herein provides in vitro testing of a Treg-inducing microparticle providing a predictable controlled release for combinations of cytokines and drugs (e.g., IL-2, TGF-β, and/or rapamycin) resulting in targeted Treg migration. These controlled release microparticles are also capable of inducing FoxP3+ Treg in human cells in vitro suggesting that these compositions be developed into an in vivo Treg induction and expansion therapy.

First claim

1 . A composition comprising:
a. a first sustained release microparticle comprising a first therapeutic agent, wherein the first therapeutic agent is selected from the group consisting of transforming growth factor beta (TGFβ), interleukin-2 (IL-2), and a combination thereof; and b. a second sustained release microparticle comprising a second therapeutic agent, wherein the second therapeutic agent is rapamycin.

2 . The composition of claim 1 , further comprising a third sustained release microparticle comprising IL-2.

3 . The composition of claim 1 , wherein the first microparticle comprises a first polymer composition and the second microparticle comprises a second polymer composition.

4 . The composition of claim 3 , wherein the first polymer composition and the second polymer composition are the same.

5 . The composition of claim 3 , wherein the first polymer composition and the second polymer composition are different.

6 . The composition of claim 1 , wherein the first and second microparticles further comprise polyethylene glycol, poly(lactide-co-glycolide) polymer (PLGA), or combination thereof.

7 . The composition of claim 3 , wherein a weight ratio of the first therapeutic agent to the first polymer composition is between about 1:100000 and about 1:1.

8 . The composition of claim 3 , wherein a weight ratio of the second therapeutic agent to the second polymer composition is between about 1:100000 and about 1:1.

9 . The composition of claim 7 , wherein the weight ratio is between about 1:20000 and 1:500.

10 . The composition of claim 8 , wherein the weight ratio is between about 1:20000 and 1:500.

11 . The composition of claim 1 , wherein the first and second microparticles have a diameter between about 200 to about 1000 nanometers.

12 . The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.

13 . A method for treating an inflammatory disorder in a subject in need thereof, the method comprising administering locally an effective amount of a composition comprising:
a. a first sustained release microparticle comprising a first therapeutic agent, wherein the first therapeutic agent is selected from the group consisting of transforming growth factor beta (TGFβ), interleukin-2 (IL-2), and a combination thereof; and b. a second sustained release microparticle comprising a second therapeutic agent, wherein the second therapeutic agent is rapamycin.

14 . The method of claim 13 , wherein the composition further comprises a third sustained release microparticle comprising interleukin-2 (IL-2).

15 . The method of claim 13 , wherein the inflammatory disorder is dermatitis.

16 . The method of claim 15 , wherein the dermatitis is an allergic contact dermatitis.

17 . The method of claim 13 , wherein the inflammatory disorder is transplant rejection.

Assignees

• Univ Pittsburgh Commonwealth Sys Higher Education

Inventors

• Little Steven R
• Raimondi Giorgio
• Thomson Angus W
• Jhunjhunwala Siddharth

Classifications

• A61K31/436 Primary

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

• A61K38/2013

  IL-2 · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/06

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

• A61K9/1641

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers · CPC title