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Metabolomics of nanoparticles lipid carriers loaded with local anesthetic in vitro

Grant number: 18/24814-0
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): September 01, 2019
Effective date (End): August 31, 2020
Field of knowledge:Health Sciences - Dentistry - Dental Clinics
Principal Investigator:Eneida de Paula
Grantee:Gustavo Henrique Rodrigues da Silva
Supervisor: Iola Melissa Fernandes Duarte
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: Universidade de Aveiro (UA), Portugal  
Associated to the scholarship:17/15174-5 - Development of functional lipid nanoparticles for the improvement of the anesthetic potency at inflamed tissues, BP.DR


Local anesthetics (AL) are drugs widely used in medical and dental clinics being capable of reversibly blocking the painful stimulus without loss of consciousness. However, in some cases AL may not have the desired effects, such as in inflamed tissues. To circumvent this situation, ALs can be encapsulated in nanostructured lipid carriers (NLC) composed of synthetic or natural excipients in order to increase their anesthetic potency. The natural excipients, besides exerting a structural function, may contribute to the therapeutics with their intrinsic anti-inflammatory properties. Nanotoxicity is one of the aspects that must be studied during the development of nanomateries design for medical application. Although NLCs are considered biocompatible, there are some reports of cytotoxicity in the literature. So, it is important to characterize their biological effects in detail. The study of metabolomics, which aims to detect metabolic changes caused by toxicological or pathophysiological stimuli, is an approach that is gaining relevance to describe mechanisms of toxicity of nanomaterials. The present project aims the study of the metabolomics of NLC carried with local anesthetics composed of synthetic and natural excipients, in order to describe their in vitro effects on cellular metabolism. In particular, we intend to: i) find the intracellular targets responsible for the cytotoxic response of neuronal cells, which help to better understand the mechanisms of action of NLC-AL, ii) characterize the immunomodulatory effects of NLC-AL on macrophages, iii) to choose the NLC less toxic and with more favorable immunomodulatory action, aiming its future clinical application.

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Scientific publications
(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)
PINTO, RICARDO J. B.; LAMEIRINHAS, NICOLE S.; GUEDES, GABRIELA; RODRIGUES DA SILVA, GUSTAVO H.; OSKOEI, PARASTU; SPIRK, STEFAN; OLIVEIRA, HELENA; DUARTE, IOLA F.; VILELA, CARLA; FREIRE, CARMEN S. R.. Cellulose Nanocrystals/Chitosan-Based Nanosystems: Synthesis, Characterization, and Cellular Uptake on Breast Cancer Cells. NANOMATERIALS, v. 11, n. 8, . (18/24814-0)
RODRIGUES DA SILVA, GUSTAVO H.; MENDES, LUIS F.; DE CARVALHO, FABIOLA, V; DE PAULA, ENEIDA; DUARTE, IOLA F.. Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells. METABOLITES, v. 12, n. 7, p. 17-pg., . (14/14457-5, 18/24814-0, 19/17784-0)

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Filed patent(s) as a result of this research project

COMPOSIÇÃO DE CARREADORES LIPÍDICOS NANOESTRUTURADOS NATURAIS COM INTRÍNSECA AÇÃO ANESTÉSICA, BACTERICIDA, ANTIFÚNGICA E BIOPESTICIDA BR1020190099216 - Universidade Estadual de Campinas (UNICAMP) ; Universidade Estadual Paulista (UNESP) . Lígia Nunes De Morais Ribeiro ; Eneida De Paula ; Simone Ramos De Castro ; Ludmilla David De Moura ; Marcelo Lancellotti ; Márcia Cristina Breitkreitz ; Viviane Aparecida Guilherme Damasio ; Gustavo Henrique Rodrigues Da Silva ; Leonardo Fernandes Fraceto ; Mônica Pascoli ; Felícia Pereira De Albuquerque ; Ricardo Antonio Polanczyk ; Daniel Junior De Andrade ; André Ricardo De Lima Damasio ; Marcelo Ventura Rubio - May 2019, 15

COMPOSIÇÃO DE CARREADORES LIPÍDICOS NANOESTRUTURADOS NATURAIS COM INSTRÍNSECA AÇÃO ANESTÉSICA PCT/BR2020/050162 - Universidade Estadual de Campinas (UNICAMP) ; Universidade Estadual Paulista Júlio de Mesquita Filho (Unesp) . Lígia Nunes de Morais Ribeiro ; Eneida De Paula ; Simone Ramos de Castro ; Ludmilla David de Moura ; Marcelo Lancellotti ; Márcia Cristina Breitkreitz ; Viviane Aparecida Guilherme Damasio ; Gustavo Henrique Rodrigues da Silva ; Andre Ricardo de Lima ; Marcelo Ventura Rubio ; Daniel Junior de Andrade ; Ricardo Antonio Polanczyk ; Felícia Pereira de Albuquerque ; Mônica Pascoli ; Leonardo Fernandes Fraceto - May 2020, 14