Nanohybrid hydrogels designed for transbuccal anesthesia

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 Bio...

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Autores principales: Ribeiro LNM, Franz-Montan M, Breitkreitz MC, Rodrigues da Silva GH, Castro SR, Guilherme VA, de Araújo DR, de Paula E
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
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Acceso en línea:https://doaj.org/article/46b6f2459d0e43a281077ccfcd57073c
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spelling oai:doaj.org-article:46b6f2459d0e43a281077ccfcd57073c2021-12-02T04:58:16ZNanohybrid hydrogels designed for transbuccal anesthesia1178-2013https://doaj.org/article/46b6f2459d0e43a281077ccfcd57073c2018-10-01T00:00:00Zhttps://www.dovepress.com/nanohybrid-hydrogels-designed-for-transbuccal-anesthesia-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Lígia 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, dentistryRibeiro LNMFranz-Montan MBreitkreitz MCRodrigues da Silva GHCastro SRGuilherme VAde Araújo DRde Paula EDove Medical PressarticleHybrid hydrogelNLCxanthanlidocaine-prilocainetopical buccal anesthesiaDentistry.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 6453-6463 (2018)
institution DOAJ
collection DOAJ
language EN
topic Hybrid hydrogel
NLC
xanthan
lidocaine-prilocaine
topical buccal anesthesia
Dentistry.
Medicine (General)
R5-920
spellingShingle Hybrid hydrogel
NLC
xanthan
lidocaine-prilocaine
topical buccal anesthesia
Dentistry.
Medicine (General)
R5-920
Ribeiro LNM
Franz-Montan M
Breitkreitz MC
Rodrigues da Silva GH
Castro SR
Guilherme VA
de Araújo DR
de Paula E
Nanohybrid hydrogels designed for transbuccal anesthesia
description 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
format article
author Ribeiro LNM
Franz-Montan M
Breitkreitz MC
Rodrigues da Silva GH
Castro SR
Guilherme VA
de Araújo DR
de Paula E
author_facet Ribeiro LNM
Franz-Montan M
Breitkreitz MC
Rodrigues da Silva GH
Castro SR
Guilherme VA
de Araújo DR
de Paula E
author_sort Ribeiro LNM
title Nanohybrid hydrogels designed for transbuccal anesthesia
title_short Nanohybrid hydrogels designed for transbuccal anesthesia
title_full Nanohybrid hydrogels designed for transbuccal anesthesia
title_fullStr Nanohybrid hydrogels designed for transbuccal anesthesia
title_full_unstemmed Nanohybrid hydrogels designed for transbuccal anesthesia
title_sort nanohybrid hydrogels designed for transbuccal anesthesia
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/46b6f2459d0e43a281077ccfcd57073c
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AT rodriguesdasilvagh nanohybridhydrogelsdesignedfortransbuccalanesthesia
AT castrosr nanohybridhydrogelsdesignedfortransbuccalanesthesia
AT guilhermeva nanohybridhydrogelsdesignedfortransbuccalanesthesia
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