Cross-linked starch-based polymers for drug-delivery

Patent metadata

Field	Value
Publication number	US-11440975-B2
Application number	US-201917049185-A
Country	US
Kind code	B2
Filing date	Apr 19, 2019
Priority date	Apr 20, 2018
Publication date	Sep 13, 2022
Grant date	Sep 13, 2022

Abstract

The invention relates a process for preparing a cross-linked starch-based polymer comprising the following steps: 1) dissolving a starchy material in a suitable solvent to form a starchy material solution; and 2) adding a episulfide of formula (I), wherein R1, R2, R3 and R4 are independently selected from hydrogen and (C1-C3)alkyl in the starchy material solution in order to obtain the disulfide crosslinked starch-based polymer. In another aspect the invention concerns a disulfide-cross-linked starch-based polymer obtainable by the process of the invention, that is characterized by only disulfide bridges.

First claim

The invention claimed is:

1. A process for preparing a disulfide cross-linked starch-based polymer comprising the following steps:
1) dissolving a starchy material in a suitable solvent to form a starchy material solution; and
2) adding an episulfide of formula (I)

wherein R 1 , R 2 , R 3 and R 4 are independently selected from hydrogen and (C 1 -C 3 )alkyl in the starchy material solution in order to obtain the disulfide crosslinked starch-based polymer, and
wherein the starchy material is selected from the group consisting of a cyclodextrin, a dextrin, a maltodextrin, and a combination thereof.

2. The process according to claim 1 , wherein the starchy material is a cyclodextrin selected from α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin.

3. The process according to claim 1 , wherein the starchy material is a maltodextrin derived from cereal starch, legume starch, or waxy maize starch.

4. The process according to claim 1 , wherein the starchy material is a maltodextrin derived from pea starch.

5. The process according to claim 4 , wherein the maltodextrin derived from pea starch has an amylose content in the range from 25% to 50% dry weight relative to the dry weight of starch.

6. The process according to claim 1 , wherein in step 1) the solvent is selected from organic aprotic polar solvents and water.

7. The process according to claim 1 , wherein step 2) is carried out at room temperature.

8. The process according to claim 1 , wherein step 2) is carried out at pH in the range from 12 to 14.

9. The process according to claim 8 , wherein the molar ratio between starchy material and the episulfide is in the ratio from 1:2 to 1:20.

10. The process according to claim 9 , wherein when the starchy material is a cyclodextrin, the ratio is 1:10, and the final disulfide cross-linked starch-based polymer is obtained by precipitation.

11. The process according to claim 9 , wherein the starchy material is a maltodextrin or a dextrin, and the ratio is 1:10.

12. The process according to claim 1 , wherein in the episulfide of formula (I), R 1 , R 2 , R 3 and R 4 are independently selected from H and CH 3 .

13. The process according to claim 12 , wherein the episulfide of formula (I) is propylene disulfide.

14. A disulfide cross-linked starch-based polymer obtainable by the process of claim 1 .

15. A method for encapsulation/inclusion/entrapment of an organic compound, wherein the method comprises the step of adding the disulfide cross-linked starch-based polymer of claim 14 with an excess of the organic compound dissolved in a solvent thus obtaining the organic compound encapsulated, included, or entrapped in the disulfide cross-linked starch-based polymer.

16. A method for encapsulating and delivering a drug, wherein said method comprises the steps of:
adding using the disulfide cross-linked starch-based polymer according to claim 14 with an excess of the drug dissolved in a solvent thus obtaining the drug encapsulated in the disulfide cross-linked starch-based polymer; and
delivering the encapsulated drug.

17. A method for hosting and delivering an anticancer drug in chemoresistant cancer cells, wherein said method comprises the steps of:
adding the disulfide cross-linked starch-based polymer according to claim 14 with an excess of the anticancer drug dissolved in a solvent thus obtaining the anticancer drug hosted in the disulfide cross-linked starch-based polymer; and
delivering the hosted anticancer drug in chemoresistant cancer cells.

Assignees

• Roquette Freres

Inventors

• Trotta Francesco
• Caldera Fabrizio

Classifications

• A61K9/4816

  Wall or shell material · CPC title

• C08B31/006 Primary

  Crosslinking of derivatives of starch · CPC title

• A61K47/6951

  using cyclodextrin (cyclodextrins used as simple excipients A61K47/40) · CPC title

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• C08L5/00

  Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00 · CPC title