Biocompatibity and permeation studies of lidocaine-loaded poly(epsilon-caprolactone) nanocapsules formulations

Abstract

The topical anesthetics avaiable do not allow painless anesthesia, considering pain due to needle insertion and injection. The use of control release systems can improve local anesthetic efficacy. Lidocaine-loaded poly(epsilon-caprolactone) nanocapules has been shown adequate stability, lower citotoxicity and sustained release, becoming a promising formulation for biocompatibility and anesthetic efficacy studies. The objectives of this study are a) to evaluate in vitro biocompatibility of oral epithelial cells and human gingival fibroblasts through the following tests: cellular viability (MTT), apoptosis (caspase-3 cleavage) and production of IL-8, TNF-± and PGE2; b) to determine in vitro lidocaine permeation in swine esophageal mucosa; c) to evaluate anesthetic efficacy in the subcutaneous infiltration in surgical wound model. The following formulations will be evaluated: 2% lidocaine, 2% lidocaine with 1:100.000 epinephrine and 2% lidocaine-loaded poly(epsilon-caprolactone) nanocapsules. 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 study will be performed in Franz vertical diffusion cells (0.6 cm2 permeation area) in swine esophageal mucosa, being compared 2% lidocaine and 2% lidocaine-loaded poly(epsilon-caprolactone) nanocapsules formulations. The anesthetic efficacy will be evaluated 24h after induction of hypernociception (surgical wound in the paw). Thirty rats (6/group) will receive 0.1mL of lidocaine 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. (AU)