Nanohybrid hydrogels designed for transbuccal anesthesia

Lígia Nunes de Morais Ribeiro; Michelle Franz-Montan; Márcia Cristina Breitkreitz; Gustavo Henrique Rodrigues da Silva; Simone Ramos de Castro; Viviane Aparecida Guilherme; Daniele Ribeiro de Araújo; Eneida de Paula

doi:10.2147/IJN.S180080

Nanohybrid hydrogels designed for transbuccal anesthesia

Int J Nanomedicine. 2018 Oct 15:13:6453-6463. doi: 10.2147/IJN.S180080. eCollection 2018.

Authors

Lígia Nunes de Morais Ribeiro¹, Michelle Franz-Montan², Márcia Cristina Breitkreitz³, Gustavo Henrique Rodrigues da Silva¹, Simone Ramos de Castro¹, Viviane Aparecida Guilherme¹, Daniele Ribeiro de Araújo⁴, Eneida de Paula¹

Affiliations

¹ Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (Unicamp), Campinas, São Paulo, Brazil, nuneslica@gmail.com.
² Department of Physiological Sciences, Piracicaba Dental School, Unicamp, Piracicaba, São Paulo, Brazil.
³ Department of Analytical Chemistry, Institute of Chemistry, Unicamp, Campinas, São Paulo, Brazil.
⁴ Human and Natural Science Center, ABC Federal University, Santo André, São Paulo, Brazil.

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.

Keywords: NLC; dentistry; hybrid hydrogel; lidocaine–prilocaine; topical buccal anesthesia; xanthan.

MeSH terms

Anesthesia*
Anesthetics, Local / administration & dosage
Anesthetics, Local / pharmacology*
Animals
Biopolymers / chemistry
Cell Line
Cell Survival / drug effects
Chemistry, Pharmaceutical / methods
Chlorocebus aethiops
Drug Liberation
Drug Stability
Female
Humans
Hydrogels / chemistry*
Lidocaine / chemistry
Lidocaine, Prilocaine Drug Combination / pharmacology
Lipids / chemistry
Male
Mice
Mouth / physiology*
Nanostructures / chemistry*
Polysaccharides, Bacterial / chemistry

Substances

Anesthetics, Local
Biopolymers
Hydrogels
Lidocaine, Prilocaine Drug Combination
Lipids
Polysaccharides, Bacterial
Lidocaine
xanthan gum