VISIBLE LIGHT CURABLE HYDROGELS AND METHODS FOR USING

• US 20140112960A1
• Filed: 10/24/2013
• Published: 04/24/2014
• Est. Priority Date: 10/24/2012
• Status: Active Grant

• Current Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Original Assignee: Indiana University Research & Technology Corporation (Indiana University)
• Inventors: LIN, Chien-Chi
• Granted Patent: US 9,364,543 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 51/1213 Semi-solid forms, gels, hydrogels, ointments, fats and waxes that are solid at room temperature
• CPC Class Codes: C08G 18/835 Unsaturated polymers modified by compounds containing a thiol group

Abstract

This disclosure provides compositions comprising a visible light-curable mixture capable of forming a biocompatible hydrogel, hydrogels prepared from the hydrogel precursor mixtures, and a biocompatible delivery system comprising a hydrogel. The disclosure also provides a process for preparing a multi layer hydrogel delivery system.

Claims

1. A composition comprising a visible light-curable mixture capable of forming a biocompatible hydrogel, the mixture comprising one or more macromers, each comprising a strained carbon-carbon multiple bond, one or more cross-linking agents, and one or more type II photoinitiators, each having at least one peak absorbance in the visible light range.

2. The composition of claim 1 wherein the peak absorbance is in the range from about 400 to about 420 nm, from about 420 to about 480 nm, from about 500 to about 530 nm, or from about 550 to about 570 nm.

3. The composition of claim 1 wherein the mixture is substantially free of co-initiators, including cytotoxic co-initiators.

4. The composition of claim 1 wherein the mixture is substantially free of co-monomers, including cytotoxic co-monomers.

5. The composition of claim 1 wherein the mixture has a rapid gel point or a rapid complete gelation time, or a combination thereof.

6. The composition of claim 1 wherein the biocompatible hydrogel exhibits low gel shear modulus or a high gel elastic modulus, or a combination thereof.

7. The composition of claim 1 wherein the mixture further comprises a therapeutic agent, a diagnostic agent, or a population of cells, or a combination thereof.

8. The composition of claim 1 wherein the biocompatible hydrogel is capable of forming a conformal gel coating for immuno-isolation of cells.

9. The composition of claim 1 wherein the photoinitiator is selected from the group consisting of eosins, Rose Bengal, riboflavins, coumarin, and 4-hydroxycoumarin, and combinations thereof.

10. The composition of claim 1 wherein the cross-linking agent is a polythiol compound.

11. The composition of claim 1 wherein the carbon-carbon multiple bond is an alkenyl group.

12. The composition of claim 1 wherein the carbon-carbon multiple bond is substantially non-polar.

13. The composition of claim 1 wherein the carbon-carbon multiple bond is in a cyclic structure.

14. The composition of claim 1 wherein the macromer comprises a polyvalent radical where each valence is attached to a poly(ethylene glycol)-norbornenyl ester.

15. The composition of claim 1 wherein the macromer comprises a polyvalent radical where each valence is attached to a poly(ethylene glycol)-norbornenyl amide.

16. The composition of claim 15 wherein the poly(ethylene glycol) has a molecular weight in the range from about 5,000 to about 40,000.

17. A biocompatible delivery system comprising a hydrogel formed from the precursor mixture of claim 1 and coating a biologically active agent.

18. The delivery system of claim 17 wherein the biologically active agent is a therapeutic agent, a diagnostic agent, or a combination thereof;

a protein or nucleic acid, or combination thereof;

an immunologic agent;

or a population of cells;

or any combination of the foregoing.

19. The delivery system of claim 17 wherein the biocompatible hydrogel is multi-layered, where each layer has independently selected characteristics.

20. A process for preparing a multi layer hydrogel delivery system, the process comprising the steps of

(a) preparing a first hydrogel from a composition according to any one of the preceding claims;

(b) optionally diffusing away at least a portion of the initiator;

(c) contacting the first hydrogel with a composition comprising one or more macromers, each comprising a carbon-carbon multiple bond, and one or more cross-linking agents according to any one of the preceding claims; and

(d) exposing the composition to visible light to form a second hydrogel layer on the first hydrogel; and

(e) optionally repeating steps (c) and (d).