Ligand-mediated controlled drug delivery
First Claim
1. A method for providing a predetermined rate of release of a biologically active agent from a carrier matrix comprising:
- providing a biologically active agent;
selecting a ligand having an affinity for the biologically active agent, wherein the ligand is selected according to a predetermined dissociation constant describing the affinity of the biologically active agent for the ligand;
incorporating the ligand into a polymeric matrix at a predetermined concentration; and
incorporating the biologically active agent into the polymeric matrix, wherein the predetermined rate of release of the biologically active agent from the polymeric matrix is established upon incorporation of the biologically active agent into the polymeric matrix, the predetermined rate of release being dependent upon the values of the dissociation constant and the ligand concentration.
2 Assignments
0 Petitions
Accused Products
Abstract
Disclosed are systems and methods that can be utilized to define and control the delivery rate of a biological agent from a carrier matrix such as a biocompatible hydrogel. The carrier matrices of the present invention can include ligands incorporated within the matrix at a predetermined concentration level (CLT). In addition, the ligands within the matrix can display a particular, predetermined affinity for the biologically active agents to be delivered by the system. In particular, the affinity between the ligand and the biologically active agent can have a known predetermined dissociation constant (KD). When utilizing the system, the agent can be incorporated within the matrix due to association of the agent with the ligand. In addition, the agent can be protected from side reactions due to the association of the agent with the ligand. Through particular selection of the parameters CLT and KD, the rate of release of the biologically active agent from the matrix can be controlled. The disclosed methods and systems can be advantageously used in both in vivo clinical settings and ex vivo settings, such as tissue engineering applications.
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Citations
47 Claims
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1. A method for providing a predetermined rate of release of a biologically active agent from a carrier matrix comprising:
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providing a biologically active agent;
selecting a ligand having an affinity for the biologically active agent, wherein the ligand is selected according to a predetermined dissociation constant describing the affinity of the biologically active agent for the ligand;
incorporating the ligand into a polymeric matrix at a predetermined concentration; and
incorporating the biologically active agent into the polymeric matrix, wherein the predetermined rate of release of the biologically active agent from the polymeric matrix is established upon incorporation of the biologically active agent into the polymeric matrix, the predetermined rate of release being dependent upon the values of the dissociation constant and the ligand concentration. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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18. A drug delivery method comprising:
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providing a biologically active agent;
selecting a ligand having an affinity for the biologically active agent, wherein the ligand is selected according to a predetermined dissociation constant describing the affinity of the biologically active agent for the ligand;
providing the ligand at a predetermined ligand concentration;
forming a complex comprising the ligand non-covalently and reversibly bound to the biologically active agent; and
incorporating the complex into a polymeric matrix, wherein a predetermined rate of release of the biologically active agent from the ligand is established upon incorporation of the complex into the polymeric matrix, the rate of release being dependent upon the predetermined dissociation constant and the ligand concentration, wherein the biologically active agent is nonreactive to the matrix and to the matrix components while held in the complex. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26)
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27. A drug delivery system configured to provide a predetermined rate of release of a biologically active agent comprising:
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a polymeric matrix;
a ligand incorporated into the polymeric matrix at a predetermined concentration, the ligand having an affinity for a biologically active agent, the affinity being described by a predetermined dissociation constant; and
the biologically active agent incorporated into the polymeric matrix by association with the ligand according to the affinity between the biologically active agent and the ligand; and
wherein the predetermined rate of release of the biologically active agent from the polymeric matrix is dependent upon the values of the dissociation constant and the ligand concentration. - View Dependent Claims (28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47)
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Specification