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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)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SANTOS, STEPHANY DI CARLA; FAVARO-MOREIRA, NADIA CRISTINA; ABDALLA, HENRIQUE BALLASSIN; XAVIER AUGUSTO, GABRIELA GAMA; COSTA, YURI MARTINS; VOLPATO, MARIA CRISTINA; GROPPO, FRANCISCO CARLOS; GILL, HARVINDER SINGH; FRANZ-MONTAN, MICHELLE. A crossover clinical study to evaluate pain intensity from microneedle insertion in different parts of the oral cavity. International Journal of Pharmaceutics, v. 592, JAN 5 2021. Web of Science Citations: 0.
SERPE, LUCIANO; MUNIZ, BRUNO VILELA; DOS SANTOS, CLEITON PITA; DA SILVA, CAMILA BATISTA; VOLPATO, MARIA CRISTINA; GROPPO, FRANCISCO CARLOS; VIANNA LOPEZ, RENATA FONSECA; FRANZ-MONTAN, MICHELLE. Full-Thickness Intraoral Mucosa Barrier Models for In Vitro Drug-Permeation Studies Using Microneedles. Journal of Pharmaceutical Sciences, v. 108, n. 5, p. 1756-1764, MAY 2019. Web of Science Citations: 1.
MUNIZ, BRUNO VILELA; BARATELLI, DIEGO; DI CARLA, STEPHANY; SERPE, LUCIANO; DA SILVA, CAMILA BATISTA; GUILHERME, VIVIANE APARECIDA; DE MORAIS RIBEIRO, LIGIA NUNES; SAIA CEREDA, CINTIA MARIA; DE PAULA, ENEIDA; VOLPATO, MARIA CRISTINA; GROPPO, FRANCISCO CARLOS; FRACETO, LEONARDO FERNANDES; FRANZ-MONTAN, MICHELLE. Hybrid Hydrogel Composed of Polymeric Nanocapsules Co-Loading Lidocaine and Prilocaine for Topical Intraoral Anesthesia. SCIENTIFIC REPORTS, v. 8, DEC 19 2018. Web of Science Citations: 2.
FRANZ-MONTAN, MICHELLE; DE MORAIS RIBEIRO, LIGIA NUNES; VOLPATO, MARIA CRISTINA; SAIA CEREDA, CINTIA MARIA; GROPPO, FRANCISCO CARLOS; TOFOLI, GIOVANA RANDOMILLE; DE ARAUJO, DANIELE RIBEIRO; SANTI, PATRIZIA; PADULA, CRISTINA; DE PAULA, ENEIDA. Recent advances and perspectives in topical oral anesthesia. Expert Opinion on Drug Delivery, v. 14, n. 5, p. 673-684, MAY 2017. Web of Science Citations: 13.
FRANZ-MONTAN, MICHELLE; SERPE, LUCIANO; MAIA MARTINELLI, CLAUDIA CRISTINA; DA SILVA, CAMILA BATISTA; DOS SANTOS, CLEITON PITA; NOVAES, PEDRO DUARTE; VOLPATO, MARIA CRISTINA; DE PAULA, ENEIDA; VIANNA LOPEZ, RENATA FONSECA; GROPPO, FRANCISCO CARLOS. Evaluation of different pig oral mucosa sites as permeability barrier models for drug permeation studies. European Journal of Pharmaceutical Sciences, v. 81, p. 52-59, JAN 1 2016. Web of Science Citations: 8.

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