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Nanohybrid hydrogels designed for transbuccal anesthesia.
Int J Nanomedicine 2018; 13:6453-6463IJ

Abstract

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 pre-anesthesia. 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.

Authors+Show Affiliations

Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil, nuneslica@gmail.com.Department of Physiological Sciences, Piracicaba Dental School, Unicamp, Piracicaba, São Paulo, Brazil.Department of Analytical Chemistry, Institute of Chemistry, Unicamp, Campinas, São Paulo, Brazil.Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil, nuneslica@gmail.com.Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil, nuneslica@gmail.com.Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil, nuneslica@gmail.com.Human and Natural Science Center, ABC Federal University, Santo André, São Paulo, Brazil.Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil, nuneslica@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30410331

Citation

Ribeiro, Lígia Nunes de Morais, et al. "Nanohybrid Hydrogels Designed for Transbuccal Anesthesia." International Journal of Nanomedicine, vol. 13, 2018, pp. 6453-6463.
Ribeiro LNM, Franz-Montan M, Breitkreitz MC, et al. Nanohybrid hydrogels designed for transbuccal anesthesia. Int J Nanomedicine. 2018;13:6453-6463.
Ribeiro, L. N. M., Franz-Montan, M., Breitkreitz, M. C., Rodrigues da Silva, G. H., de Castro, S. R., Guilherme, V. A., ... de Paula, E. (2018). Nanohybrid hydrogels designed for transbuccal anesthesia. International Journal of Nanomedicine, 13, pp. 6453-6463. doi:10.2147/IJN.S180080.
Ribeiro LNM, et al. Nanohybrid Hydrogels Designed for Transbuccal Anesthesia. Int J Nanomedicine. 2018;13:6453-6463. PubMed PMID: 30410331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nanohybrid hydrogels designed for transbuccal anesthesia. AU - Ribeiro,Lígia Nunes de Morais, AU - Franz-Montan,Michelle, AU - Breitkreitz,Márcia Cristina, AU - Rodrigues da Silva,Gustavo Henrique, AU - de Castro,Simone Ramos, AU - Guilherme,Viviane Aparecida, AU - de Araújo,Daniele Ribeiro, AU - de Paula,Eneida, Y1 - 2018/10/15/ PY - 2018/11/10/entrez PY - 2018/11/10/pubmed PY - 2018/12/18/medline KW - NLC KW - dentistry KW - hybrid hydrogel KW - lidocaine–prilocaine KW - topical buccal anesthesia KW - xanthan SP - 6453 EP - 6463 JF - International journal of nanomedicine JO - Int J Nanomedicine VL - 13 N2 - 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 pre-anesthesia. 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. SN - 1178-2013 UR - https://www.unboundmedicine.com/medline/citation/30410331/Nanohybrid_hydrogels_designed_for_transbuccal_anesthesia L2 - https://dx.doi.org/10.2147/IJN.S180080 DB - PRIME DP - Unbound Medicine ER -