Hydrogel inclusion complex including physiologically active material bound to thermosensitive poly(phosphazene) by host-guest interaction using beta-cyclodextrin and use thereof

Patent metadata

Field	Value
Publication number	US-2025163223-A1
Application number	US-202519019853-A
Country	US
Kind code	A1
Filing date	Jan 14, 2025
Priority date	Jun 19, 2019
Publication date	May 22, 2025
Grant date	—

Abstract

Provided is a hydrogel composition including thermosensitive poly(phosphazene) to which a plurality of hydrophobic amino acids, hydrophilic polymers, and host molecules are substituted; and a physiologically active material linked to a guest molecule, wherein the poly(phosphazene) and the physiologically active material form a conjugate by inclusion of the guest molecule in the host molecule via a host-guest interaction.

First claim

We claim:

1 . A method of controlling stem cell differentiation comprising treating stem cells with a hydrogel thermosensitive poly(phosphazene) that comprises repeat units including a hydrophobic amino acid side chain, a hydrophilic polymer sidechain, and a side chain including beta-cyclodextrin, and a stem cell differentiation regulator linked directly or via a linker to one or more guest molecules selected from the group consisting of adamantine, azobenzene, cholesterol, tert-butyl, cyclohexyl ester, and naphthyl.

2 . The method of claim 1 , wherein the guest molecule is conjugated to all or part of the beta-cyclodextrin by inclusion of the guest molecule into the beta-cyclodextrin via a host-guest interaction.

3 . The method of claim 1 , wherein the thermosensitive poly(phosphazene) and the stem cell differentiation regulator linked directly or via a linker to one or more guest molecules are provided separately or in the form of a complex which is formed by forming a conjugate by inclusion of the guest molecule in the beta-cyclodextrin via a host-guest interaction.

4 . The method of claim 1 , wherein the stem cell differentiation regulator maintains stemness of the stem cells, or affects the stem cells to be differentiated to a specific state by controlling the type or ratio of the stem cell differentiation regulator.

5 . The method of claim 1 , wherein the stem cell differentiation regulator is a peptide comprising arginine-glycine-aspartic acid (RGD).

6 . The method of claim 1 , wherein the stem cell differentiation regulator is a peptide comprising CESPLKRQ and a peptide comprising CLRAHAVDIN, and the hydrogel thermosensitive poly(phosphazene) induces differentiation into chondrocytes.

7 . The method of claim 1 , wherein the stem cell differentiation regulator is a protein selected from the group consisting of BMP, N-cadherin, insulin-like growth factor (IGF), fibroblast growth factor (FGF), and transforming growth factor β (TGF-β).

8 . The method of claim 1 , wherein the stem cell differentiation regulator is transforming growth factor β (TGF-β) to facilitate cartilage-specific gene expression.

9 . The method of claim 2 , further comprising injecting the hydrogel thermosensitive poly(phosphazene) into damaged tissue, wherein the stem cell differentiation regulator promotes tissue regeneration.

10 . The method of claim 9 , further comprising injecting stem cells into the damaged tissue.

11 . A method of inhibiting cancer cell proliferation or metastasis in a patient, the method comprising administering to a patient in need thereof a hydrogel thermosensitive poly(phosphazene) that comprises repeat units including a hydrophobic amino acid side chain, a hydrophilic polymer sidechain, and a side chain including beta-cyclodextrin, and Interleukin-2 linked directly or via a linker to one or more guest molecules selected from the group consisting of adamantine, azobenzene, cholesterol, tert-butyl, cyclohexyl ester, and naphthyl,
wherein the guest molecule is conjugated to all or part of the beta-cyclodextrin by inclusion of the guest molecule into the beta-cyclodextrin via a host-guest interaction.

12 . The method of claim 11 , wherein the administering to the patent comprises injecting the hydrogel thermosensitive poly(phosphazene) directly into or proximate to the cancer tumor of the patient.

Assignees

• Korea Inst Sci & Tech

Inventors

• Song Soo Chang
• Hong Ki Hyun

Classifications

• C08J3/245

  Differential crosslinking of one polymer with one crosslinking type, e.g. surface crosslinking · CPC title

• C08G2210/00

  Compositions for preparing hydrogels · CPC title

• A61K9/5036

  Polysaccharides, e.g. gums, alginate; Cyclodextrin · CPC title

• A61K38/04

  Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof ({enzyme inhibitors A61K38/005;} gastrins {A61K38/2207}, somatostatins A61K38/31, melanotropins A61K38/34 {; protease inhibitors A61K38/55}) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title