(572b) Use Marker Pen to Constantly Release Tetrodotoxin at Nanogram Level

Tetrodotoxin (TTX) is an effective non-protein specific blocker of voltage-gated sodium (NaV) channels. TTX is 1000-fold more potent than clinically used anesthetics such as bupivacaine and lidocaine. In addition, TTX does not cause myotoxicity or neurotoxicity, has no affinity with the myocardial NaV channels, and does not penetrate the blood-brain barrier to cause drug addiction. All these features make TTX an attractive candidate for painkiller design. However, the principal reason why TTX has not yet achieved clinical application is its systemic toxicity. The TTX overdose causes neural blockade and muscular weakness resulting in diaphragmatic paralysis leading to respiratory arrest and death. Therefore, the final and most critical milestone of TTX clinical practice is to precisely control the dose of TTX to take advantage of its therapeutic effects but avoid its systemic toxicity. Inspired by the marker pen, which stores the water-based ink in the spongy core and always releases a constant amount of ink from the tip for writing, we explored the marker pen for TTX controlled release. We have verified that the marker pen can encapsulate water-soluble drugs in the pen core by absorbing the drug aqueous solution, and release a constant amount of drug per unit length of the line drawn with the pen tip. In addition, the drug concentration in the filling drug aqueous solution can be infinitely diluted to achieve the constant release of drug at the nanogram level or less (such a low level makes TTX super safe to use). The marker pen is equipped with a pen stopper to prevent leakage of drug. We also demonstrated that the drug-filled pen has a super-long shelf life as evidenced that the amount of drug released from the pen 6 months after filling is the same as that of a newly filled pen. One practical application of the marker pen filled with TTX is a topical anesthetic, which is used to treat skin pain.