There is clinical and scientific interest in developing local anesthetics with prolonged durations of effect from single injections. The need for such is highlighted by the current opioid epidemic. Site 1 sodium channel blockers such as tetrodotoxin (TTX) are extremely potent, and can provide very long nerve blocks but the duration is limited by the associated systemic toxicity. Here we report a system where slow release of TTX conjugated to a biocompatible and biodegradable polymer, poly(triol dicarboxylic acid)-co-poly(ethylene glycol) (TDP), is achieved by hydrolysis of ester linkages. Nerve block by the released TTX is enhanced by administration in a carrier with chemical permeation enhancer (CPE) properties. TTX release can be adjusted by tuning the hydrophilicity of the TDP polymer backbone. In vivo, 1.0–80.0 µg of TTX released from these polymers produced a range of durations of nerve block, from several hours to 3 days, with minimal systemic or local toxicity.
Tissue bioadhesives are widely used in dermatology, surgery rooms, and in the field. Despite their advantages over sutures and staples, currently available tissue glues are limited by their mechanical properties and toxicity. Here, a new approach is described for wound closure that is based on a biocompatible, low melting point four-armed N-hydroxy succinimide-modified polycaprolactone (star-PCL-NHS). Star-PCL-NHS is inserted into a hot melt glue gun, melts upon minimal pressure, and is extruded directly onto the wound, where it solidifies, bonding strongly with both edges of the wound. Changes in molecular weight allow control of adhesive strength, melting point, and elasticity properties. In vitro and in vivo evaluations confirm the biocompatibility of this system. The straightforward synthetic scheme and the simple delivery method, combined with the desirable mechanical properties, tunability, and tissue compatibility, are desirable traits in wound management.
An on-demand anesthetic that would only take effect when needed and where the intensity of anesthesia could be easily adjustable according to patients’ needs would be highly desirable. Here, we design and synthesize a macromolecular prodrug (P407-CM-T) in which the local anesthetic tetracaine (T) is attached to the polymer poloxamer 407 (P407) via a photo-cleavable coumarin linkage (CM). P407-CM-T solution is an injectable liquid at room temperature and gels near body temperature. The macromolecular prodrug has no anesthetic effect itself unless irradiated with a low-power blue light emitting diode (LED), resulting in local anesthesia. By adjusting the intensity and duration of irradiation, the anesthetic effect can be modulated. Local anesthesia can be repeatedly triggered.
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