TY - JOUR
T1 - A crossover clinical study to evaluate pain intensity from microneedle insertion in different parts of the oral cavity
AU - Di Carla Santos, Stephany
AU - Fávaro-Moreira, Nádia Cristina
AU - Abdalla, Henrique Ballassin
AU - Augusto, Gabriela Gama Xavier
AU - Costa, Yuri Martins
AU - Volpato, Maria Cristina
AU - Groppo, Francisco Carlos
AU - Gill, Harvinder Singh
AU - Franz-Montan, Michelle
N1 - Funding Information:
Financial support was provided by the São Paulo Research Foundation (FAPESP, grants #2012/06974-4 and #2015/50004-8). S.C.S. received a masters’ scholarship from FAPESP (#2016/24057-0). HSG was partially supported by the National Institutes of Health (NIH) [grant numbers R01AI121322 and R01AI135197] and in part by funding from Texas Tech University.
Funding Information:
Financial support was provided by the S?o Paulo Research Foundation (FAPESP, grants #2012/06974-4 and #2015/50004-8). S.C.S. received a masters? scholarship from FAPESP (#2016/24057-0). HSG was partially supported by the National Institutes of Health (NIH) [grant numbers R01AI121322 and R01AI135197] and in part by funding from Texas Tech University.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1/5
Y1 - 2021/1/5
N2 - 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.
AB - 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.
KW - Clinical trial
KW - Drug delivery
KW - Microneedles
KW - Oral mucosa
KW - Topical administration
KW - Transmucosal
UR - http://www.scopus.com/inward/record.url?scp=85096535597&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2020.120050
DO - 10.1016/j.ijpharm.2020.120050
M3 - Article
C2 - 33161036
AN - SCOPUS:85096535597
VL - 592
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 120050
ER -