Polymerizing Insulin with Photocleavable Linkers to Make Light-Sensitive Macropolymer Depot Materials

The use of light-sensitive polymers for the release of therapeutics is an important approach allowing the timing and amount of the release to be controlled precisely. The use of light has been pioneered to control insulin release from a dermal photoactivated depot, or PAD. One of the main impediments to the use of light-sensitive polymers in this context is the density of the materials: The large majority of the material is the carrier polymer, with the minority being the therapeutic. In this work, the feasibility of using insulin itself as a monomer in the polymerization process is demonstrated. Insulin modified with either one or two light cleavable azide groups is polymerized with a tridentate alkyne-bridging monomer using a click reaction. The resulting material called a "macropolymer" is ≈85% insulin, is insoluble in aqueous solvent, and releases native, soluble insulin upon irradiation.