Local anesthetics are the most used drugs to control trans and postoperatory pain in medicine and dentistry. Along with their toxicity to cardiovascular and central nervous system they can exert a variety a effects on cells, interfering with healing, inflammation and causing cytotoxicity. Control release systems, such as polymeric nanocarriers have been proposed to reduce drug toxicity and enhance biodisponibility. Therefore, the objectives of this study are: 1) to evaluate in vitro biocompatibility of oral epithelial cells and human gingival fibroblasts through the following tests: cellular viability (MTT), apoptosis (Flow cytometric and caspase-3 cleavage) and production of IL-8, TNF-± and PGE2; 2) to determine in vitro articaine permeation in swine esophageal mucosa; 3) to evaluate anesthetic efficacy in the subcutaneous infiltration in surgical wound model. The following formulations will be evaluated: 2% articaine without additive, solution of 2% articaine with 1:200.000 epinephrine, 2% articaine-loaded poly(epsilon-caprolactone) nanocapules and 2% articaine-loaded poly(epsilon-caprolactone) nanocapules with 1:200.000 epinephrine, together with their respective controls: solution of NaCl 0.9%, saline solution with epinephrine,poly(epsilon-caprolactone) nanocapules without local anesthetic, poly(epsilon-caprolactone)nanocapules with epinephrine and 4% articaine with 1:200.000 epinephrine. For in vitro biocompatibility study the cells will be exposed to different concentrations of the anesthetic formulations for 1h and 24h; quantification of cytokines and PGE2 will be performed by using the capture ELISA test. The permeation of vasoconstrictor free articaine formulations in swine esophageal mucosa will be performed in Franz vertical diffusion cells (0.6 cm2 permeation area). The anesthetic efficacy will be evaluated 24h after induction of hypernociception (surgical wound in the paw). Fifty-four rats (6/group) will receive 0.1mL of articaine formulations or the respective control laterally to the wound. Anesthesia will be evaluated by force application with von Frey anesthesiometer. Statistical analysis will be performed by ANOVA or Kruskal-Wallis test, considering 5% of significance level.
News published in Agência FAPESP Newsletter about the scholarship: