Development, biocompatibility and permeation studies on gel formulations of poly-epsilon-caprolactone nanocapsules containing local anesthetics

Abstract

The topical anesthetics available in Dentistry do not allow painless local anesthesia, considering pain due to needle insertion and injection. The use of control release systems can improve local anesthetic efficacy. Lidocaine-prilocaine loaded poly(epsilon-caprolactone) nanocapsules has been shown adequate stability, high encapsulation efficiency and sustained release, becoming a promising formulation for biocompatibility and anesthetic efficacy studies. The objectives of this study are a) the characterization of gel-based formulations of lidocaine-prilocaine loaded poly-epsilon-caprolactone nanocapules: rheology, drug concentration and pH; b) In vitro biocompatibility evaluation of oral epithelial cells and human gingival fibroblasts through the following tests: cell viability (MTT), apoptosis (caspase-3 cleavage) and production of IL-8, TNF-± and PGE2; c) in vitro permeation of local anesthetics from gel formulations across pig esophageal and palatal mucosa, measured in Franz type diffusion cells; d) evaluation of in vivo anesthetic efficacy by using Tail Flick test, in rats. Two different gels will be evaluated for the association with the lidocaine-prilocaine loaded poly-epsilon-caprolactone nanocapsules: Carbopol Ultrex® base and Aristoflex AVC® base. Both gel formulations will be compared to the commercially available mixture of 2.5% lidocaine and prilocaine called EMLA®, AstraZeneca), as well as with non encapsulated local anesthetics gel formulations, for all the experimental protocols proposed in the present project. Therefore, the present study aims at the development of more efficacious and biocompatible formulations for Dentistry use. The topical anesthetics available in Dentistry do not allow painless local anesthesia, considering pain due to needle insertion and injection. The use of control release systems can improve local anesthetic efficacy. Lidocaine-prilocaine loaded poly(epsilon-caprolactone) nanocapsules has been shown adequate stability, high encapsulation efficiency and sustained release, becoming a promising formulation for biocompatibility and anesthetic efficacy studies. The objectives of this study are a) the characterization of gel-based formulations of lidocaine-prilocaine loaded poly-epsilon-caprolactone nanocapules: rheology, drug concentration and pH; b) the evaluation of accelerated stability of the formulations; c) In vitro biocompatibility evaluation of oral epithelial cells and human gingival fibroblasts through the following tests: cell viability (MTT), apoptosis (caspase-3 cleavage) and production of IL-8, TNF-± and PGE2; d) in vitro permeation of local anesthetics from gel formulations across pig esophageal and palatal mucosa, measured in Franz type diffusion cells; e) evaluation of in vivo anesthetic efficacy by using Tail Flick test, in rats. Two different gels will be evaluated for the association with the lidocaine-prilocaine loaded poly-epsilon-caprolactone nanocapsules: Carbopol Ultrex® base and Aristoflex AVC® base. Both gel formulations will be compared to the commercially available mixture of 2.5% lidocaine and prilocaine called EMLA®, AstraZeneca), as well as with non encapsulated local anesthetics gel formulations, for all the experimental protocols proposed in the present project. Therefore, the present study aims at the development of more efficacious and biocompatible formulations for Dentistry use, and also to start the research line involving permeation studies of topical formulations used in Dentistry. (AU)