Tetracaine Hydrochloride

TTC can induce cytotoxicity on several cell lines mainly via apoptosis, a form of PCD that features nuclear fragmentation, plasma membrane blebbing, and the shrinking and fragmentation of cells into apoptotic bodies. TTC has been found to trigger the canonical and non-canonical inflammatory pathways by activating caspase-1 and caspase-11, respectively. Caspase-1 and caspase-11, when activated, go on to cleave GSDMD into GSDMD-C and GSDMD-N. The GSDMD-N can then oligomerize to create GSDMD pores on the cell membrane which would induce pyropotosis in macrophages. IL-1β is then activated by caspase-1 and released through the GSDMD pores. Inhibiting the treatment of caspase-1 and caspase-11 by Beln and Wede could greatly reduce TTC-induced caspase-1 and caspase-11 cleavage, respectively, which subsequently abrogates TTC induced upregulation of GSDMD-N and macrophagic pyrotosis.

Fig. 1 Schematic diagram of the mechanism of TTC-induced macrophage pyroptosis. (Zhang R, et al. 2023)

For the improvement of needle-free dentistry, a novel hybrid delivery approach has been recently formulated. The drug used is 4% Tetracaine (TTC), a local anesthetic. The 4% TTC is loaded onto nanostructured lipid carriers (NLC) to form a hybrid drug delivery system by incorporation into a thermoreversible poloxamer 407 hydrogel for intranasal administration. This device was primarily developed to take advantage of the highly permeable nasal mucosa and its use to anesthetize maxillary teeth by acting directly on the pain source as well as addressing some of the issues faced by spray formulations that include mucociliary clearance and mucosal irritation.
This novel hybrid hydrogel showed good mucoadhesive and rheological properties that make it transition into a gel form at body temperature. In this way, a greater residence time in the intended site of administration was also achieved. In addition, the NLC-hydrogel composite allowed a better controlled release of the active agent with a more reduction in cellular toxicity than the free drug. The in vivo study of the composite system showed a three-fold increase in the duration of analgesia and better permeation through the nasal tissues. The incorporation of TTC-loaded hybrid hydrogel for painless anesthetic effect in the field of dentistry could serve as a long-lasting, simple, safe, and topically applied alternative, thus improving patient anxiety towards dental injections.

Fig. 2 Nanostructured lipid carriers containing tetracaine for local, intranasal needle-free anesthesia. (Calixto G M F, et al. 2021)