Giovana Radomille Tofoli

Publications (2)4.15 Total impact

• Article: Improvement of tetracaine antinociceptive effect by inclusion in cyclodextrins.

  Roberta Aline Franco de Lima, Marcelo Bispo de Jesus, Cíntia Maria Saia Cereda, Giovana Radomille Tofoli, Luis Fernando Cabeça, Irineu Mazzaro, Leonardo Fernandes Fraceto, Eneida de Paula
  [show abstract] [hide abstract]
  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.
  Journal of Drug Targeting 11/2011; 20(1):85-96. · 2.70 Impact Factor
• Article: Pharmacokinetic and local toxicity studies of liposome-encapsulated and plain mepivacaine solutions in rats.

  Giovana Radomille Tofoli, Cíntia Maria Saia Cereda, Daniele Ribeiro de Araujo, Eneida de Paula, Rui Barbosa Brito, José Pedrazzoli, Eduardo Meurer, Fábio Alessandro Proença Barros, Francisco Carlos Groppo, Maria Cristina Volpato, José Ranali
  [show abstract] [hide abstract]
  ABSTRACT: The pharmacokinetics and the local toxicity of commercial and liposome-encapsulated mepivacaine formulations injected intra-orally in rats were studied. Animals were divided in groups (n = 4-6) and treated with 0.1 mL of the formulations: 2% mepivacaine with 1:100,000 epinephrine (MVC(2%EPI)), 3% mepivacaine (MVC(3%)), and 2% liposome-encapsulated mepivacaine (MVC(LUV)). The results showed that the 2% liposome-encapsulated mepivacaine reduced C(max), prolonged AUC(0-infinity) and t(1/2) compared with 3% plain and 2% vasoconstritor-associated mepivacaine, after intraoral injection. In addition, it was also observed that liposomal mepivacaine might protect the tissue against local inflammation evoked by plain or vasoconstrictors-associated mepivacaine, giving supporting evidence for its safety and possible clinical use in dentistry.
  Drug Delivery 02/2010; 17(2):68-76. · 1.46 Impact Factor