MARGARETH KAZUYO KOBAYASHI DIAS FRANCO

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2018 - 20202
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Fator de Impacto: 4.500 - 5.999 × Assunto: calorimetry ×

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    Artigo IPEN-doc 27384
    Capsaicin-cyclodextrin complex enhances mepivacaine targeting and improves local anesthesia in inflamed tissues
    2020 - COUTO, VERONICA M.; OLIVEIRA-NASCIMENTO, LAURA de; CABEÇA, LUIZ F.; GERALDES, DANILO C.; COSTA, JULIANA S.R.; RISKE, KARIN A.; FRANZ-MONTAN, MICHELLE; YOKAYCHIYA, FABIANO; FRANCO, MARGARETH K.K.D.; PAULA, ENEIDA de
    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-β-CD), as shown by the phase solubility study. The resulting complex (HP-β-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 1H-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.
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    Artigo IPEN-doc 24763
    Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release
    2018 - NASCIMENTO, M.H.M.; FRANCO, M.K.K.D.; YOKAICHYIA, F.; PAULA, E. de; LOMBELLO, C.B.; ARAUJO, D.R. de
    In this study,we reported the hyaluronic acid (HA) on supramolecular structure of Pluronic F-127 (PLF-127) and/ or Pluronic F-108 (PLF-127) hydrogels, as well as their effects on release mechanisms, looking forward their application as lidocaine (LDC) drug-delivery systems in arthroplastic surgeries.We have studied the HA-micelle interaction using Dynamic Light Scattering (DLS), themicellization and sol-gel transition processes by Differential Scanning Calorimetry (DSC) and Rheology., of PL-based hydrogels and. The presence of HA provided the formation of larger micellar dimensions from ~26.0 to 42.4 nm. The incorporation of HA did not change the micellization temperatures and stabilized hydrogels rheological properties (G′ N G″), showing no interference on PLthermoreversible properties. Small-Angle-X-ray Scattering (SAXS) patterns revealed that HA incorporation effects were pronounced for PLF-127 and PLF-108 systems, showing transitions from lamellar to hexagonal phase organization (HA-PLF-127) and structural changes from cubic to gyroid and/or cubic to lamellar. The HA insertion effects were also observed on drug release profiles, since lower LDC release constants (Krel = 0.24–0.41 mM·h−1) were observed for HA-PLF-127, that presented a hexagonal phase organization. Furthermore, the HA-PL systems presented reduced in vitro cytotoxic effects, pointed out their tendency to selfassembly and possible application as drug delivery systems.