Fig. 1.

Design of a sustained release system for prolonged duration local anesthesia. a A polymer–TTX conjugate, designed to have a large TTX content with slow release, is placed near a nerve. Flux of TTX into the nerve is enhanced by a delivery system that acts as a chemical permeation enhancer. The polymer–TTX conjugate, schematized here as a hyperbranched structure has a much higher TTX loading than those actually produced here (which have 0.008 or 0.03 TTX molecules on each polymer chain). b Steglich esterification to synthesize TDP and TDP–TTX. The first step is optional, depending on whether the PEG moiety needs to be incorporated into the polymer