Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same
The present disclosure generally provides complexes including a pharmaceutically active agent and a functionalized polymer, wherein the functionalized polymer includes repeat units, the repeat units including ionizable repeat units having at least one ionizable side group and/or ionizable end group, a plurality of the at least one ionizable groups forming non-covalent bonds with the pharmaceutically active agent. Polymers which may be used to form such complexes as well as methods of making and using the complexes and related compositions are also provided.
1. A method comprising:
providing a precursor polymer comprising repeat units, the repeat units comprising functionalizable repeat units comprising at least one functionalizable side group;
obtaining a functionalized polymer by transforming, using click chemistry, said functionalizable repeat units into ionizable repeat units comprising at least one ionizable side group; and
combining the functionalized polymer with a pharmaceutically active agent to form a complex in which a plurality of the at least one ionizable side group forms a plurality of non-covalent bonds with the pharmaceutically active agent.
2. The method of claim 1 , wherein said transforming, using click chemistry, comprises effecting a cycloaddition reaction.
3. The method of claim 2 , wherein said cycloaddition reaction is a Diels-Alder cycloaddition reaction.
4. The method of claim 2 , wherein said cycloaddition reaction is a Huisgen 1,3-dipolar cycloaddition reaction.
5. The method of claim 2 , wherein said cycloaddition reaction is a cycloaddition reaction between an azide and an alkyne to form a linkage comprising a 1,2,3-triazole.
6. The method of claim 1 , wherein the at least one functionalizable side group is an azido group and wherein the transforming, using click chemistry, comprises reacting the precursor polymer with an alkyne to form the functionalized polymer, the functionalized polymer comprising at least one 1,2,3-triazole ring.
7. The method of claim 1 , wherein the at least one functionalizable side group is a leaving group and wherein the transforming, using click chemistry, comprises: (a) transforming the leaving group into an azido group and thereby providing a polymer intermediate; and (b) reacting the polymer intermediate with an alkyne to form the functionalized polymer, the functionalized polymer comprising at least one 1,2,3-triazole ring.
8. The method of claim 1 , wherein the at least one functionalizable side group is an alkynyl group and wherein the transforming, using click chemistry, comprises reacting the precursor polymer with an azide to form the functionalized polymer, the functionalized polymer comprising at least one 1,2,3-triazole ring.
9. The method of claim 1 , wherein the transforming, using click chemistry, comprises a monovalent copper catalyzed reaction or a ruthenium catalyzed reaction.
10. The method of claim 1 , wherein the transforming, using click chemistry, comprises a copper catalyzed azide-alkyne cycloaddition reaction.