A crossover clinical study to evaluate pain intensity from microneedle insertion in different parts of the oral cavity

Author(s)

Santos, Stephany Di Carla ^[1] ; Favaro-Moreira, Nadia Cristina ^[1] ; Abdalla, Henrique Ballassin ^{[2, 1]} ; Xavier Augusto, Gabriela Gama ^[1] ; Costa, Yuri Martins ^[1] ; Volpato, Maria Cristina ^[1] ; Groppo, Francisco Carlos ^[1] ; Gill, Harvinder Singh ^[3] ; Franz-Montan, Michelle ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Biosci, Sao Paulo - Brazil

^[2] Inst & Ctr Pesquisas Sao Leopoldo Mandic, Fac Sao Leopoldo Mandic, Lab Neuroimmune Interface Pain Res, Campinas, SP - Brazil

^[3] Texas Tech Univ, Dept Chem Engn, 8th St & Canton Ave, Mail Stop 3121, Lubbock, TX 79409 - USA

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 592, JAN 5 2021.
• Web of Science Citations: 0

Abstract

The objective of the present study was to evaluate discomfort and safety of microneedle (MN) insertion in several intraoral regions. A device was developed to standardize MN insertions. MNs were inserted in the following regions of the oral cavity: gingiva, palatine alveolar process, buccal mucosa, dorsum of the tongue and inner portion of the lower lip. Perforations from MNs post insertion were confirmed with topical gentian violet stain. Pain was evaluated in a randomized, double-blinded, crossover study in 30 volunteers. Each volunteer received a MN patch, a 30G hypodermic needle (positive control) and an identical MN patch with its needles laying flat in the plane of the patch (negative control). Adverse events were visually evaluated immediately after (0 h) and 24 h post MN application. The application device developed a consistent application force (10 N) and promoted perforation of all individual MNs on a patch. At all sites, insertion of the hypodermic needle promoted more pain when compared to the negative control (p < 0.001). Application of the MNs promoted less pain than the hypodermic needle (p < 0.05), but slightly more pain as compared to the negative control (p < 0.05) at all sites except the tongue, where the MN did not differ from the negative control (p > 0.05). Hypodermic needle caused bleeding at all insertion sites. In contrast, MNs did not cause bleeding at most sites except in some cases of insertion into the hard gingiva and the palatine alveolar process where tiny blood spots appeared immediately after MN application for few of the MNs on the patch. There were no cases of bleeding at 24 h post MN application. In conclusion, MNs can perforate different sites of the oral cavity in a safe and significantly less painful manner as compared to the 30G hypodermic needle. Thus, analogous to the skin, MN-based approaches could be an attractive approach for drug delivery in the oral cavity. (AU)

• FAPESP's process: 16/24057-0 - Evaluation of pain after topical application of microneedles at the oral cavity of healthy volunteers
• Grantee: Stephany di Carla Santos
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/06974-4 - Development, biocompatibility and permeation studies on gel formulations of poly-epsilon-caprolactone nanocapsules containing local anesthetics
• Grantee: Michelle Franz Montan Braga Leite
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/50004-8 - Evaluation of pain and anesthetic efficacy after topical application of microneedles: a randomized clinical trial
• Grantee: Michelle Franz Montan Braga Leite
• Support Opportunities: Regular Research Grants