Gels and multilayer surface structures from boronic acid containing polymers

• US 6,652,902 B2
• Filed: 12/28/2001
• Issued: 11/25/2003
• Est. Priority Date: 08/27/1998
• Status: Expired due to Term

• Current Assignee: ETH Zurich, Universität Zürich
• Original Assignee: ETH Zurich, Universität Zürich
• Inventors: Hubbell, Jeffrey A., Elbert, Donald L., Winblade, Natalie D.
• Primary Examiner(s): Nakarani, D. S.
• Application Number:
  US10/035,625
• Publication Number:
  US 20020061288A1
• Time in Patent Office: 697 Days
• Field of Search: 424/422, 424/423, 424/424, 424/425, 424/426, 428/473, 427/2.1, 427/2.11, 427/2.12, 427/2.24, 427/2.25, 427/2.26, 427/2.28, 427/2.3, 427/2.31, 427/389, 427/498, 427/517
• US Class Current: 427/2.11
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: C08L 71/02 Polyalkylene oxides

Abstract

Boronic acid containing polymers are used to form bioinert gels and multilayer surface structures. These polymers form crosslinked hydrogels, which are highly swollen in water. The crosslinking can either be chemical or physical. Water soluble polymers containing boronic acid groups, such as phenylboronic acid (PBA), can be physically crosslinked by mixing the polymers in water with other polymers containing hydroxyls or carboxylic acids. Alternatively, surfaces can be treated by stepwise incubation with a solution of the boronic acid containing polymer, followed by incubation with a solution of a diol or carboxylic acid containing polymer. Many successive layers can be generated, increasing the thickness of the formed structure at each step. The bioinert gel or surface coating can be used for passivating the surfaces of medical implants (especially those based on transplanted tissue), or for passivating the surfaces of tissues in situ, decreasing the incidence or severity of such pathologic conditions as the formation of post-surgical adhesions, and thrombosis following angioplasty.

Claims

1. A method for coating, encansulating, plugging, sealing, or supporting a surface, comprising depositing a polyner containing more than one boronic acid group onto the surface, wherein the surface comprises more than one hydroxyl or carboxylic acid functional group which crosslinks with the boronic acid,

applying to the polymer containing more than one boronic acid group a layer of a polymer containing more than one hydroxyl or carboxylic acid functional group to form a multi-layer structure, and

alternately repeating the steps of depositing the polymer containing more than one boronic acid group and applying the polymer containing more than one hydroxyl or carboxylic acid functional group to form additional layers of the multi-layer structure.

2. A method for coating, encapsulating, plugging, sealing, or supporting a surface, comprising depositing a polymer containing more than one boronic acid group onto the surface, wherein the surface comprises more than one hydroxyl or carboxylic acid functional group which crosslinks with the boronic acid, wherein the surface is a cell or tissue surface.

3. The method of claim 2 wherein the polymer containing more than one boronic acid group is applied postoperatively, or during angioplasty, to minimize or prevent postoperative adhesion, thrombosis, or to encourage healing or prevent infection.

4. The method of claim 2 wherein the polymer containing more than one boronic acid group has coupled to or incorporated therein an agent selected from the group consisting of therapeutic, diagnostic or prophylactic agents, comprising applying the polymer to a site for delivery of the agent.

5. A method for coating, encapsulating, plugging, sealing, or supporting a surface, comprising depositing a polymer containing more than one boronic acid group onto the surface, wherein the surface comprises more than one hydroxyl or carboxylic acid functional group which crosslinks with the boronic acid, and wherein the polymer containing more than one boronic acid group is applied to cancer cells to minimize metastasis of the cells.