Hybrid nanofilms as topical anesthetics for pain-free procedures in dentistry

Lígia N M Ribeiro,Simone R Castro,Gustavo H Rodrigues Da Silva,Ana C S Alcântara,Bruno V Muniz,Michelle Franz-Montan,Viviane A Guilherme,Eneida De Paula,Márcia C Breitkreitz

doi:10.1038/s41598-020-68247-0

Abstract

Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. So far, there are no commercially available effective topical anesthetic formulations for that purpose, and the most of developments are related to hydrophilic and low mucoadhesive forms. Therefore, we have prepared different hybrid nanofilms composed of biopolymer matrices (chitosan, pectin, and chitosan-pectin) blended with nanostructured lipid carriers (NLC) loading the eutectic mixture of 5% lidocaine–prilocaine (LDC–PLC), in order to fulfill this gap in the market. These dual systems were processed as hybrid nanofilms by the solvent/casting method, and its mucoadhesive, structural and mechanical properties were detailed. The most appropriate hybrid nanofilm combined the advantages of both pectin (PCT) and NLC components. The resultant material presented sustained LDC–PLC release profile for more than 8 h; permeation across porcine buccal mucosa almost twice higher than control and non-cytotoxicity against 3T3 and HACAT cell lines. Then, the in vivo efficacy of PCT/NLC formulation was compared to biopolymer film and commercial drug, exhibiting the longest-lasting anesthetic effect (> 7 h), assessed by tail flick test in mice. These pectin-based hybrid nanofilms open perspectives for clinical trials and applications beyond Dentistry.

Highlights

Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity
In 2016, we have described detailed structural information regarding the development of nanostructured lipid carriers (NLC) loading lidocaine– prilocaine (LDC–PLC) (5%)
The hybrid nanofilms composed of CHT/NLC and CHT–PCT/NLC were friable and the lipid excipient was disposed as white clusters at the biopolymers films surfaces

Summary

Introduction

Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. We have prepared different hybrid nanofilms composed of biopolymer matrices (chitosan, pectin, and chitosan-pectin) blended with nanostructured lipid carriers (NLC) loading the eutectic mixture of 5% lidocaine– prilocaine (LDC–PLC), in order to fulfill this gap in the market. These dual systems were processed as hybrid nanofilms by the solvent/casting method, and its mucoadhesive, structural and mechanical properties were detailed. The in vivo efficacy of PCT/ NLC formulation was compared to biopolymer film and commercial drug, exhibiting the longestlasting anesthetic effect (> 7 h), assessed by tail flick test in mice These pectin-based hybrid nanofilms open perspectives for clinical trials and applications beyond Dentistry. There are only a few descriptions of polymer films[22,23,24,25,26] in comparison to hydrogels for topical LA delivery[27]

Methods

Results

Discussion

Conclusion