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Lidocaine and epinephrine co-loaded mucoadhesive liquid crystal precursor systems as a strategy for topical anesthesia in the buccal cavity

Grant number: 19/07245-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2019
Effective date (End): September 30, 2021
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Michelle Franz Montan Braga Leite
Grantee:Giovana Maria Fioramonti Calixto Balian
Home 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

Abstract

Local anesthesia is required for most dental procedures. However, due to its route of administration, local anesthesia is painful and can cause withdrawal of phobic patients and consequently, promote discontinuation of dental treatment, impairing their oral health. Thus, many dentists perform topical anesthesia prior to local anesthesia to minimize the discomfort of the injection. However, many studies have shown that commercial topical anesthetics do not completely minimize the pain of needle penetration and injection of anesthetic solution and thus one of the most anticipated innovations in Dentistry is the development of an effective topical anesthetic formulation. Thus, the development of a nanostructured liquid crystal mucoadhesive precursor systems (LCPS) for the topical administration of lidocaine (LDC) and epinephrine (EPI) emerges as a valuable and innovative strategy, since this system is capable of incorporating two drugs in addition to increasing permeation the oral mucosa and control the release of them. Thus, LCPS can overcome the oral mucosal barrier and effectively prevent the transduction of pain signals. In addition, LCPS is interesting for buccal topical administration because it can be applied in the liquid state, gelling and becoming a mucoadhesive liquid crystalline system upon contact with saliva. Therefore, the objective of this study is to develop, characterize and evaluate the toxicity and anesthetic efficacy of lidocaine and epinephrine co-incorporated into mucosal LCPS as a strategy for topical anesthesia in the oral cavity. LCPS constituted by ethoxylated ethoxylated 20 alcohol and propoxylated 5, oleic acid and chitosan containing LDC and EPI will be characterized by polarized light microscopy, low angle X-ray scattering, test of gelling in contact with artificial saliva, rheology tests, in vitro mucoadhesion test, texture profile analysis, swelling tests, in vitro release and permeation assays, and stability. Subsequently, the toxicity of LCPS will be investigated using the Galleria mellonella larva model and the chicken embryo chorioallantoic membrane (CAM) model. Finally, the anesthetic efficacy of LCPS will be assessed in vivo in the tail-removal model in rats. In this way, we intend to obtain an effective and biocompatible nanostructured release system for use in topical anesthesia in Dentistry.