Antitumor effects of plain and 2-hydroxypropyl-²-cyclodextrin lidocaine and articaine formulations on in vitro and in vivo models.

Abstract

Local anesthetics (LA) have shown anti-proliferative, cytotoxic, apoptotic, and anti-inflammatory effects. Effects of LA on different cancer cell types have been reported. However, their use is restrict due the intrinsic toxicity on the central nervous system and the short duration. Complexation into cyclodextrins demonstrated improvements in local anesthetics aqueous solubility and others biopharmaceutical properties. The aim of this study is to evaluate the antitumor effects of plain and hydroxypropyl-²-cyclodextrin (HP-²-CD) lidocaine and articaine formulations, in vitro and in vivo. Squamous carcinoma cells (SCC9 e SCC25), HeLa, human keratinocytes (HaCaT), and fibroblasts cells (HGF) will be exposed to plain and HP-²-CD lidocaine and articaine formulations. Anti-proliferative activity, cytotoxicity, apoptosis, loss of mitochondrial potential and inflammatory mediators release will be evaluated in vitro. For the in vivo test, lidocaine formulations will be tested against Walker 256 carcinoma. The cells will be seed in the plantar region of the right hind paw of male Wistar rats. Three days after, 0.2 mL of HP-²-CD lidocaine or 5% lidocaine will be injected (interplantar). Doxorubicin will be inject (intraperitoneal) as positive control. The animals' weight, edema size and tumor weight will be measured daily. The interplantar tissue will be collected for histological analyzes, pro-inflammatory cytokines and prostaglandin E2 quantification by ELISA, and proteins related to proliferation and apoptosis by western blot. (AU)