Development of fast-dissolving microneedles for topical administration of lidocaine and epinephrine in the oral cavity

• Grant number: 25/10249-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Michelle Franz Montan Braga Leite
• Grantee: Arthur Antunes Costa Bezerra
• Supervisor: Ryan Donnelly
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
• Institution abroad: Queen's University Belfast, Northern Ireland
• Associated to the scholarship: 24/11199-7 - Assessment of the applicability of the chicken embryo chorioallantoic membrane (CAM) model in toxicity and permeation studies of topical anesthetics, BP.DR

Abstract

Topical drug administration in the oral cavity represents a significant challenge, as the epithelial layer of the mucosa lining this cavity constitutes a considerable barrier to diffusion. Moreover, it is difficult to maintain the formulation at the site of application due to the continuous action of saliva and the mechanical movements associated with speaking, chewing, and swallowing. Consequently, to achieve intratissue therapeutic effects, local injection is often required in the treatment of various clinical conditions, which are generally painful and uncomfortable for patients, as is the case with local anesthesia. In this context, topical dental anesthesia has proven ineffective in most cases, necessitating injectable local anesthesia to perform painless procedures. Given this scenario, new strategies have been developed to overcome these limitations, with microneedle (MN) systems standing out. Therefore, the present study aims to develop a polymeric MN matrix containing lidocaine and epinephrine, with ultrarapid dissolution in the oral mucosa, intended for use as a topical dental anesthetic. The most suitable polymers for the incorporation of lidocaine and epinephrine (at concentrations of 2.5% and 0.05%, respectively) will be evaluated, focusing on obtaining systems with ultrarapid dissolution (within 30 seconds) while ensuring the stability of the components. Subsequently, specific assays will be conducted for the characterization of the formulations: evaluation of mechanical and insertion properties, determination of MN dissolution time, and estimation of drug content. Following this stage, which will be carried out during the research internship abroad, the developed systems will undergo the following tests in Brazil: evaluation of in vitro permeation capacity through porcine buccal mucosa; in vivo toxicity assay using the chick embryo chorioallantoic membrane (CAM) model; and, if time permits, an in vivo anesthetic efficacy test (Tail Flick test). This project is expected to result in the development of an innovative microneedle system with ultrarapid dissolution, co-loaded with lidocaine (LDC) and epinephrine (EPI), intended for topical dental anesthesia. The microneedles should exhibit adequate mechanical strength for insertion into the oral mucosa, ultrarapid dissolution compatible with clinical practice, and consistent, quantifiable drug content. (AU)