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Thermoreversible hydrogel containing tetracaine loaded in nanostructured lipid carriers for topical intranasal delivery

Grant number: 18/25920-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): March 01, 2019
Effective date (End): August 31, 2019
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Michelle Franz Montan Braga Leite
Grantee:Bruno Vilela Muniz
Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , 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


One of the great achievements in dentistry was the development of local anesthetics, which allow the accomplishment of painless dental treatment in most cases. However, administration of the anesthetic involves puncture of the tissue with needles and injection of the solution, which are painful procedures and strongly induce stress to patients. To minimize this discomfort, topical anesthetics are applied at the site prior to injection. However, despite the improvement in the quality of surface anesthesia induced by formulations lately developed, they are not effective for all types of anesthesia. Several advances have been achieved in the development of topical topical anesthetics for more effective topical use involving drug delivery systems. Among these systems, nanostructured lipid carriers (CLNs) are able to solubilize lipophilic actives, decrease toxicity and maintain the effect of in the target tissue for longer. The poloxamer 407 hydrogel (PL407) has thermoreversible and bioadhesive properties of great importance to prolong the residence time of the formulations, especially on the mucosal surface. Considering the possibility of achieving pulpal anesthesia through topical application, the literature demonstrates that the application of tetracaine associated with topical oxymetazoline, via the intranasal route, promotes pulpal anesthesia of maxillary teeth, including this combination was approved by the FDA in 2016 and marketed in the United States under the name KOVANAZE® (St. Renatus, LLC). In this way, this is a promising route for this purpose and little explored in the literature. In this sense, this project intends to evaluate if the performance of tetracaine is improved by its encapsulation in nanostructured lipid carriers dispersed in a thermo-reversible hydrogel based on PL407 (formulation previously developed and characterized in Dissertation defended linked to the present Thematic project) aiming at its future administration topical via the intranasal route with the aim of promoting pulpal anesthesia of maxillary teeth. Toxicity assays in culture of human glioblastoma cells (LN229); analysis of mechanical properties in vitro; ex vivo mucoadhesion assay, and evaluation of the permeation ability of the formulation through the nasal mucosa in Franz type vertical diffusion cells. The formulation is expected to exhibit low toxicity, good mechanical and mucoadhesive properties, and high ability to permeate the nasal mucosa.

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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)
CALIXTO, GIOVANA MARIA FIORAMONTI; MUNIZ, BRUNO VILELA; CASTRO, SIMONE R.; DE ARAUJO, JAIZA SAMARA MACENA; AMORIM, KLINGER DE SOUZA; RIBEIRO, LIGIA N. M.; FERREIRA, LUIZ EDUARDO NUNES; DE ARAUJO, DANIELE RIBEIRO; DE PAULA, ENEIDA; FRANZ-MONTAN, MICHELLE. Mucoadhesive, Thermoreversible Hydrogel, Containing Tetracaine-Loaded Nanostructured Lipid Carriers for Topical, Intranasal Needle-Free Anesthesia. PHARMACEUTICS, v. 13, n. 11, . (18/25920-9, 19/07245-5, 14/14457-5)

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