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Title: Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues
Author: Couto, Verônica Muniz; Paula, Eneida De; Oliveira-nascimento, Laura De; Cabeça, Luiz Fernando; Geraldes, Danilo Costa; Costa, Juliana Souza Ribeiro; Riske, Karin A.; Franz-montan, Michelle; Yokaychiya, Fabiano; Franco, Margareth K. K. Dias
Year: 2020
Is part of: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, p. 5741 -
DOI: https://doi.org/10.3390/ijms21165741

Citation: Couto, Verônica Muniz; Paula, Eneida De; Oliveira-nascimento, Laura De; Cabeça, Luiz Fernando; Geraldes, Danilo Costa; Costa, Juliana Souza Ribeiro; Riske, Karin A.; Franz-montan, Michelle; Yokaychiya, Fabiano; Franco, Margareth K. K. Dias; Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, p. 5741-, 2020

Abstract: Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-beta-CD), as shown by the phase solubility study. The resulting complex (HP-beta-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and(1)H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.

Keywords: capsaicin; cyclodextrins; drug delivery; local anesthetics;
Subjects: CIENCIAS_BIOLOGICAS; Biofísica de Processos e Sistemas; CIENCIAS_BIOLOGICAS; Farmacologia; Farmacologia Bioquímica e Molecular;


Funding: This research was funded by Fapesp (grant #2015/11804-9, #2014/14457-5, #14/20224-3) and financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brasil (CAPES)-Finance Code 001.
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