Significance: We demonstrate an injectable drug-delivery system that would allow patients to adjust the timing, duration, and intensity of local anesthesia in painful parts of the body. Such on-demand analgesia could greatly enhance the management of a variety of pain states. Light-sensitive liposomes containing the potent local anesthetic tetrodotoxin induced sensory and motor nerve block in vivo upon irradiation with a 730-nm laser. The timing, duration, and intensity of the nerve blockade were adjustable by the timing, irradiance, and duration of irradiation. Tissue reaction to the formulation and associated irradiation was benign.

Injectable materials often have shortcomings in mechanical and drug‐eluting properties that are attributable to their high water contents. A water‐free, liquid four‐armed PEG modified with dopamine end groups is described which changes from liquid to elastic solid by reaction with a small volume of Fe³⁺ solution. The elastic modulus and degradation times increase with increasing Fe³⁺ concentrations. Both the free base and the water‐soluble form of lidocaine can be dissolved in the PEG₄‐dopamine and released in a sustained manner from the cross‐linked matrix. PEG₄‐dopamine is retained in the subcutaneous space in vivo for up to 3 weeks with minimal inflammation. This material's tailorable mechanical properties, biocompatibility, ability to incorporate hydrophilic and hydrophobic drugs and release them slowly are desirable traits for drug delivery and other biomedical applications.