MARGARETH KAZUYO KOBAYASHI DIAS FRANCO
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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.Artigo IPEN-doc 23142 An abraded surface of doxorubicin-loaded surfactant-containing drug delivery systems effectively reduces the survival of carcinoma cells2016 - SCHMIDT, CHRISTIAN; YOKAICHYIA, FABIANO; DOGANGUZEL, NURDAN; FRANCO, MARGARETH K.K.D.; CAVALCANTI, LEIDE P.; BROWN, MARK A.; ALKSCHBIRS, MELISSA I.; ARAUJO, DANIELE R. de; KUMPUGDEE-VOLLRATH, MONT; STORSBERG, JOACHIMAn effective antitumor remedy is yet to be developed. All previous approaches for a targeted delivery of anticancer medicine have relied on trial and error. The goal of this study was to use structural insights gained from the study of delivery systems and malignant cells to provide for a systematic approach to the development of next-generation drugs. We used doxorubicin (Dox) liposomal formulations. We assayed for cytotoxicity via the electrical current exclusion method. Dialysis of the samples yielded information about their drug release profiles. Information about the surface of the delivery systems was obtained through synchrotron small-angle X-ray scattering (SAXS) measurements. SAXS measurements revealed that Dox-loading yielded an abraded surface of our Dox liposomal formulation containing soybean oil, which also correlated with an effective reduction of the survival of carcinoma cells. Furthermore, a dialysis assay revealed that a higher burst of Dox was released from soybean oil-containing preparations within the first five hours. We conclude from our results that an abraded surface of Dox-loaded drug delivery system increases their efficacy. The apparent match between surface geometry of drug delivery systems and target cells is suggested as a steppingstone for refined development of drug delivery systems. This is the first study to provide a systematic approach to developing next-generation drug carrier systems using structural insights to guide the development of next-generation drug delivery systems with increased efficacy and reduced side effects.Artigo IPEN-doc 22486 Enhancement of chlorpromazine antitumor activity by pluronics F127/L81 nanostructured system against human multidrug resistant leukemia2016 - MELLO, JOYCE C. de; MORAES, VIVIAN W.R.; WATASHI, CAROLINA M.; SILVA, DEYSE C. da; CAVALCANTI, LEIDE P.; FRANCO, MARGARETH K.K.D.; YOKAICHIYA, FABIANO; ARAUJO, DANIELE R. de; RODRIGUES, TIAGOThe development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics®) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy.