Nanohybrid hydrogels designed for transbuccal anesthesia
Received 13 July 2018
Accepted for publication 23 August 2018
Published 15 October 2018 Volume 2018:13 Pages 6453—6463
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Thomas Webster
Lígia Nunes de Morais Ribeiro,1 Michelle Franz-Montan,2 Márcia Cristina Breitkreitz,3 Gustavo Henrique Rodrigues da Silva,1 Simone Ramos de Castro,1 Viviane Aparecida Guilherme,1 Daniele Ribeiro de Araújo,4 Eneida de Paula1
1Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil; 2Department of Physiological Sciences, Piracicaba Dental School, Unicamp, Piracicaba, São Paulo, Brazil; 3Department of Analytical Chemistry, Institute of Chemistry, Unicamp, Campinas, São Paulo, Brazil; 4Human and Natural Science Center, ABC Federal University, Santo André, São Paulo, Brazil
Background: Local anesthesia in dentistry is by far the most terrifying procedure for patients, causing treatment interruption. None of the commercially available topical formulations is effective in eliminating the pain and phobia associated to the needle insertion and injection.
Materials and methods: In this work we prepared a nanostructured lipid-biopolymer hydrogel for the sustained delivery of lidocaine–prilocaine (LDC-PLC) for transbuccal preanesthesia. The lipid was composed of optimized nanostructured lipid carriers (NLC) loaded with 5% LDC-PLC (NLC/LDC-PLC). The biopolymer counterpart was selected among alginate, xanthan (XAN), and chitosan matrices. The XAN-NLC hydrogel presented the most uniform aspect and pseudoplastic rheological profile, as required for topical use; therefore, it was selected for subsequent analyses. Accelerated stability tests under critical conditions (40°C; 75% relative humidity) were conducted for 6 months, in terms of drug content (mg/g), weight loss (%), and pH.
Results: In vitro LDC-PLC release profile through Franz diffusion cells revealed a bimodal kinetics with a burst effect followed by the sustained release of both anesthetics, for 24 hours. Structural analyses (fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy) gave details on the molecular organization of the hybrid hydrogel, confirming the synergic interaction between the components. Safety and efficacy were evaluated through in vitro cell viability (3T3, HaCat, and VERO cells) and in vivo antinociceptive (tail-flick, in mice) tests, respectively. In comparison to a control hydrogel and the eutectic mixture of 5% LDC-PLC cream (EMLA®), the XAN-NLC/LDC-PLC hybrid hydrogel doubled and quadrupled the anesthetic effect (8 hours), respectively.
Conclusion: Considering such exciting results, this multifaceted nanohybrid system is now ready to be further tested in clinical trials.
Keywords: hybrid hydrogel, NLC, xanthan, lidocaine–prilocaine, topical buccal anesthesia, dentistry
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