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Development of functional lipid nanoparticles for the improvement of the anesthetic potency at inflamed tissues

Grant number: 17/15174-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2017
Effective date (End): July 31, 2022
Field of knowledge:Health Sciences - Dentistry - Dental Clinics
Principal researcher:Eneida de Paula
Grantee:Gustavo Henrique Rodrigues da Silva
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics, AP.TEM
Associated scholarship(s):18/24814-0 - Metabolomics of nanoparticles lipid carriers loaded with local anesthetic in vitro, BE.EP.DR

Abstract

Local Anesthetics (LA) are drugs widely used in medical and dental clinics 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. In dental anesthesia, anesthetic failure or a lower degree of analgesia may occur in places with pulpitis or periodontitis processes installed. In these cases, the clinical treatment of these pathologies becomes extremely painful, stressful and without alternatives for the effective control of pain. Anesthetic failure is mainly explained by mechanisms of acidosis and hyperalgesia, both of which are caused by the inflammatory process. Thus, the present project proposes the development of optimized nanostructured lipid carrier formulations (composed of natural excipients) for the sustained release of Anesthetics Articaine (ART) and Butamben (BTB). These excipients, in addition to exerting structural function, will contribute to the therapeutics with their intrinsic anti-inflammatory properties. Butamben is a long-acting AL, low solubility and does not ionize in acidic medium; Articaine is a fast acting agent, widely used in dentistry. Through the nanoencapsulation of these AL, we hope to increase its bioavailability and, more specifically, to articaine, its availability in the neutral form (bypassing the limitation of the anesthetic action imposed by local acid pH) and also increase its anesthetic potency (necessary in hyperalgesia), without Increase of toxicity. To achieve these objectives, the NLC-ART and NLC-BTB systems will be optimized by experimental design through the analysis of parameters: particle size/number, polydispersity index, Zeta potential and encapsulation efficiency of anesthetics. The NLCs will be characterized by DSC, DRX, TEM, encapsulation efficiency and in vitro release profile of AL. The physical-chemical stability of the formulations will be monitored for 1 year. The systems will be evaluated for cellular internalization and anesthetic potency, through the in vivo study of analgesia, in a model of induced inflammation. (AU)

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Scientific publications (6)
(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)
RODRIGUES DA SILVA, GUSTAVO H.; PAES LEMES, JULIA BORGES; GERONIMO, GABRIELA; DE LIMA, FERNANDO FREITAS; DE MOURA, LUDMILLA DAVID; DOS SANTOS, ARIANY CARVALHO; CARVALHO, NATHALIA SANTOS; MALANGE, KAUE FRANCO; BREITKREITZ, MARCIA C.; PARADA, CARLOS A.; et al. Lipid nanoparticles loaded with butamben and designed to improve anesthesia at inflamed tissues dagger. BIOMATERIALS SCIENCE, v. 9, n. 9, p. 3378-3389, . (17/15174-5, 14/25372-0)
DA SILVA, GUSTAVO H. RODRIGUES; GERONIMO, GABRIELA; GARCIA-LOPEZ, JUAN P.; RIBEIRO, LIGIA N. M.; DE MOURA, LUDMILLA D.; BREITKREITZ, MARCIA C.; FEIJOO, CARMEN G.; DE PAULA, ENEIDA. Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish. SCIENTIFIC REPORTS, v. 10, n. 1, . (14/14457-5, 17/15174-5)
GERONIMO, GABRIELA; RODRIGUES DA SILVA, GUSTAVO H.; DE MOURA, LUDMILLA D.; RIBEIRO, LIGIA N. M.; GUILHERME, VIVIANE A.; MENDONCA, TALITA C.; CASTRO, SIMONE R.; BREITKREITZ, MARCIA C.; DE PAULA, ENEIDA. Development of S75:R25 bupivacaine-loaded lipid nanoparticles functionalized with essential oils for treating melanoma. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 8, p. 2197-2207, . (14/14457-5, 18/07100-4, 17/15174-5)
RODRIGUES DA SILVA, GUSTAVO HENRIQUE; DE MOURA, LUDMILLA DAVID; DE CARVALHO, FABIOLA VIEIRA; GERONIMO, GABRIELA; MENDONCA, TALITA CESARIM; DE LIMA, FERNANDO FREITAS; DE PAULA, ENEIDA. Antineoplastics Encapsulated in Nanostructured Lipid Carriers. Molecules, v. 26, n. 22, . (19/17784-0, 21/02617-1, 18/12121-0, 20/01237-8, 17/15174-5)
PRATES, ERICA TEIXEIRA; RODRIGUES DA SILVA, GUSTAVO HENRIQUE; SOUZA, THAIS F.; SKAF, MUNIR S.; PICKHOLZ, MONICA; DE PAULA, ENEIDA. Articaine interaction with phospholipid bilayers. Journal of Molecular Structure, v. 1222, . (14/14457-5, 17/15174-5, 07/02629-2)
RODRIGUES DA SILVA, GUSTAVO H.; GERONIMO, GABRIELA; RIBEIRO, LIGIA N. M.; GUILHERME, VIVIANE A.; DE MOURA, LUDMILLA DAVID; BOMBEIRO, ANDRE L.; OLIVEIRA, JULIANA DAMASCENO; BREITKREITZ, MARCIA C.; DE PAULA, ENEIDA. Injectable in situ forming nanogel: A hybrid Alginate-NLC formulation extends bupivacaine anesthetic effect. Materials Science & Engineering C-Materials for Biological Applications, v. 109, . (18/07100-4, 14/25372-0, 17/15174-5, 14/14457-5)

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