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Type: Artigo de periódico
Title: Improvement Of Tetracaine Antinociceptive Effect By Inclusion In Cyclodextrins.
Author: Franco de Lima, Roberta Aline
de Jesus, Marcelo Bispo
Saia Cereda, Cíntia Maria
Tofoli, Giovana Radomille
Cabeça, Luis Fernando
Mazzaro, Irineu
Fraceto, Leonardo Fernandes
de Paula, Eneida
Abstract: Local anesthetics (LA) are among the most important pharmacological compounds used to attenuate or eliminate pain. However, systemic toxicity is still a limitation for LA application, especially for ester-type drugs, such as tetracaine (TTC) that presents poor chemical stability (due to hydrolysis by plasma esterases). Several approaches have been used to improve LA pharmaceutical properties, including the employment of drug-delivery systems. Here we used beta-cyclodextrin (β-CD) or hydroxypropyl-beta-cyclodextrin (HP-β-CD) to develop two new TTC formulations (TTC:β-CD and TTC:HP-β-CD). The inclusion complexes formation, in a 1:1 stoichiometry, was confirmed by differential scanning calorimetry, X-ray diffraction, UV-VIS absorption and fluorescence. Nuclear magnetic resonance (DOSY experiments) revealed that TTC association with HP-β-CD is stronger (Ka=1200 mol/L(-1)) than with β-CD (Ka=845 mol/L(-1)). Moreover, nuclear Overhauser effect (NOE) experiments provided information on the topology of the complexes, where TTC aromatic ring is buried inside the CD hydrophobic cavity. In vitro tests with 3T3 fibroblast cells culture revealed that complexation decreased TTC cytotoxicity. In addition, the total analgesic effect of TTC, tested in rats through the infraorbital nerve test, was improved in 36% with TTC:β-CD and TTC:HP-β-CD. In conclusion, these formulations presented potential for future clinical use, by reducing the toxicity and increasing the antinociceptive effect of tetracaine.
Subject: Analgesics
Chemistry, Pharmaceutical
Nih 3t3 Cells
Pain Measurement
Rats, Wistar
X-ray Diffraction
Rights: fechado
Identifier DOI: 10.3109/1061186X.2011.622400
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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