Ligand-coupled initiator polymers and methods of use

Abstract

Initiator polymers having an initiator group and a ligand group are provided. The initiator polymers are capable of specifically binding to a receptor on a surface. Using a macromer system, the initiator polymers are useful for the formation of a polymeric matrix on the surface of a material. In particular, initiator polymers are provided that have specificity to pancreatic β cells and can be used to encapsulate cells for transplantation and the treatment of diabetes.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]The present non-provisional patent application is a divisional of U.S. patent application Ser. No. 10 / 412,063, filed on Apr. 10, 2003, now U.S. Pat. No. 7,820,158, entitled LIGAND-COUPLED INITIATOR POLYMERS AND METHODS OF USE, which is fully incorporated herein by reference.FIELD OF THE INVENTION[0002]The current invention relates to compounds useful for forming a polymeric matrix on the surface of a substrate. More specifically, the invention relates to initiator polymers that can specifically bind to a target surface and promote formation of a polymeric matrix on the surface.BACKGROUND[0003]The use of polymeric material for the encapsulation of cells and tissue offers great potential for the treatment of diseases and other medical indications. Particularly useful applications involve utilizing polymeric material for encapsulating tissues or cells for transplantation into a patient in order to provide therapy. Although various techniques ...

AI Technical Summary

Benefits of technology

The ligand-coupled initiator polymers enable the formation of a stable, biocompatible polymeric matrix on cell surfaces, reducing toxicity and improving encapsulation efficiency, while allowing for specific cellular responses, such as insulin production, and providing immunoprotection for transplanted cells.

Problems solved by technology

Unfortunately, there are a number of problems associated with this approach to cell encapsulation.

Such problems include the swelling of alginate microcapsules due to the presence of Ca2+ in the inner alginate core, insufficient biocompatibility due to guluronic acid content in alginate / polylysine capsules, and insufficient mechanical strength of the alginate coating.

Moreover, the process of alginate encapsulation is nonspecific and can result in the formation of microcapsules that do not contain the cells or cell groups intended to be encapsulated or that contain other non-target biological materials.

However, the use of eosin Y, which is a relatively nonpolar, low molecular weight light-activated initiator dye, or compounds similar to eosin, presents many disadvantages for interfacial polymerization methods and also presents potential problems to subjects receiving transplanted encapsulated cells.

For example, these dyes and other similar low molecular weight compounds present toxicity problems as they can penetrate into a cell and interfere with normal biochemical pathways.

If penetrated into the cell, these dyes can cause free radical damage when activated by external sources of energy.

Other drawbacks arise if the dye is able to diffuse out of the formed polymeric layer, thereby producing potential toxicity to a host organism.

Dyes such as eosin also tend to aggregate in aqueous solution, thereby reducing the efficiency of the encapsulation process and introducing problems with reproducibility.

Finally, in view of the limited efficiency of these dyes in initiating sufficient radical chain polymerization, it is often necessary to add one or more monomeric polymerization “accelerators” to the polymerization mixture.

The cell surface, to which the initiator polymer is targeted, is very complex and presents a challenge for the design of initiators that function in a desired manner.

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