Polymer-drug conjugates

A method for controllably releasing a conjugate within subcutaneous tissue in response to the local concentration of an indicator comprising subcutaneously administering, to a patient in need thereof, a material that comprises:

• a plurality of conjugates that each include a drug covalently linked to a polymer that includes an analog of the indicator within its covalent structure, wherein said conjugates are susceptible to digestion by an enzyme present in the extracellular space of subcutaneous tissue;
• and
• a plurality of multivalent cross-linking agents each containing two or more cross-link receptors, wherein said conjugates are cross-linked by said multivalent cross-linking agents through interactions between the indicator analogs and the cross-link receptors, wherein said interactions are competitively disrupted if an amount of the indicator is present, and wherein competitive disruption of the interactions between the indicator analogs and the cross-link receptors causes the material to release the conjugate in a manner that is dependent on the local concentration of the indicator.

A method for treating diabetes comprising subcutaneously administering to a patient in need thereof, a material that comprises:

• a plurality of conjugates that each include an antidiabetic agent covalently linked to a polymer that includes an analog of glucose within its covalent structure, wherein said conjugates are susceptible to digestion by an enzyme present in the extracellular space of subcutaneous tissue;
• a plurality of multivalent cross-linking agents each comprising containing two or more cross-link receptors, wherein said conjugates are cross-linked by said multivalent cross-linking agents through interactions between the glucose analogs and the cross-link receptors, wherein said interactions are competitively disrupted if an amount of glucose is present, and wherein competitive disruption of the interactions between the glucose analogs and the cross-link receptors causes the material to release the conjugate in a manner that is dependent on the local concentration of glucose.

A method for treating diabetes comprising subcutaneously administering to a patient in need thereof, a material that comprises:

• a plurality of conjugates that each include insulin covalently linked to glycogen;
• a plurality of multivalent cross-linking agents each comprising a Con A molecule covalently modified with a polyethylene, wherein said conjugates are cross-linked by said multivalent cross-linking agents through interactions between glycogen and the Con A molecules, wherein said interactions are competitively disrupted if an amount of glucose is present, and wherein competitive disruption of the interactions between glycogen and the Con A molecules causes the material to release the conjugate in a manner that is dependent on the local concentration of glucose.