MARGARETH KAZUYO KOBAYASHI DIAS FRANCO

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2017 - 20182
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Fator de Impacto: 1.500 - 2.999 × Assunto: drug delivery ×

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    Artigo IPEN-doc 24321
    Effects of doxorubicin on the structural and morphological characterization of solid lipid nanoparticles (SLN) using small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS)
    2018 - YOKAICHIYA, FABIANO; SCHMIDT, CHRISTIAN; STORSBERG, JOACHIM; VOLLRATH, MONT K.; ARAUJO, DANIELE R. de; KENT, BEN; CLEMENS, DANIEL; WINGERT, FRIEDRICH; FRANCO, MARGARETH K.K.D.
    Cancer is still a major public health problem. Leaving detection of early stages of tumors and other issues aside, minimizing unwarranted side effects, for example after clinical usage of a liposomal anticancer drug doxorubicin (Dox) formulation, is an unmet clinical problem and the focus of many studies. Using compounds typically used in the preparation of food and/or cosmetics to prepare drug carrier systems, we observed that sodium tetradecyl sulfate (STS) containing and soybean-oil based carriers are more efficient in reducing the viability of HeLa cells tumor cells in comparison to their respective counterparts. Here, we probe the doxorubicin (Dox) loading on structural properties of either soybean oil or coconut oil (Mygliol 812) formulations. Small angle neutron scattering (SANS) assays were performed using V16 instrument at Helmholtz-Zentrum Berlin (HZB) at 25, 37 and 40 C with two or 11m distance between detector and sample to assess a wide range in scattering vector Q. Combined with previous measurement using small angle X-ray scattering (SAXS), our results show that the Dox has different influence in the surface structure of the solid lipid nanoparticles (SLN) and also affects the fractality in the vesicle aggregates when the concentration of the drug is altered, for Mygliol and soybean oil SLN drug delivery carrier systems.
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    Artigo IPEN-doc 23189
    Complexation of oxethazaine with 2-hydroxypropyl-bcyclodextrin: increased drug solubility, decreased cytotoxicity and analgesia at inflamed tissues
    2017 - PRADO, ANDRESSA R.; YOKAICHYIA, FABIANO; FRANCO, MARGARETH K.K.D.; SILVA, CAMILA M.G. da; OLIVEIRA-NASCIMENTO, LAURA; FRANZ-MONTAN, MICHELLE; VOLPATO, MARIA C.; CABECA, LUIS F.; PAULA, ENEIDA de
    ObjectivesOxethazaine (OXZ) is one of the few local anaesthetics that provides analgesia at low pH, but presents poor solubility, cytotoxicity and no parenteral formulations. To address these issues, we aimed to prepare OXZ host-guest inclusion complex with hydroxypropyl-beta-cyclodextrin (HP--CD). MethodsThe inclusion complex was formed by co-solubilization, followed by a job plot analysis to determine stoichiometry of complexation and dialysis equilibrium analysis (based on UV/VIS absorption and fluorescence profiles of OXZ). Complex formation was confirmed by phase-solubility data, X-ray, Scanning Electron Microscopy and DOSY-H-1-NMR experiments. In vitro cytotoxicity was analysed by MTT test in 3T3 fibroblasts. In vivo analgesia was tested by Von Frey test (inflammatory wounds - rats). Key findingsOxethazaine complexed (1 : 1 molar ratio) with HP--CD, as indicated by loss of OZX crystalline structure (X-ray) and strong host: guest interaction (NMR, K = 198/M), besides increased solubility. In vitro cell survival improved with the complex (IC50 OXZ = 28.9 m, OXZ : HP--CD = 57.8 m). In addition, the complex (0.1% OXZ) promoted in vivo analgesia for the same time that 2% lidocaine/epinephrine did. Conclusion Our results show that complexation improved physicochemical and biological properties of OXZ, allowing its application to inflamed tissues by parenteral routes.