Sandra Elisa Haas

Cutaneous melanoma: new advances in treatment

Cutaneous melanoma is a challenge to treat. Over the last 30 years, no drug or combination of drugs demonstrated significant impact to improve patient survival. From 1995 to 2000, the use of cytokines such as interferon and interleukin become treatment options. In 2011, new drugs were approved by the U.S. Food and Drug Administration, including peginterferon alfa-2b for patients with stage III disease, vemurafenib for patients with metastatic melanoma with the BRAF V600E mutation, and ipilimumab, a monoclonal antibody directed to the CTLA-4 T lymphocyte receptor, to combat metastatic melanoma in patients who do not have the BRAF V600E mutation. Both ipilimumab and vemurafenib showed results in terms of overall survival. Other trials with inhibitors of other genes, such as the KIT gene and MEK, are underway in the search for new discoveries. The discovery of new treatments for advanced or metastatic disease aims to relieve symptoms and improve patient quality of life.

A surface modification of clozapine-loaded nanocapsules improves their efficacy: A study of formulation development and biological assessment.

This work aimed to develop nanocapsules (NC) coated with polysorbate 80 (P80), cationic chitosan (CS) or polyethylene glycol (PEG) using clozapine (CZP) as the drug model. The zeta potential, pH and encapsulation efficiency were directly affected by the CS coating. Using the bag dialysis method, the in vitro CZP release from CS-coated nanocapsules was similar to the PEG-coated at pH 7.4. Nanocapsules coated with PEG and CS exhibited an increased action duration compared to the P80-coated nanocapsules in pseudo-psychosis induced by d,l-amphetamine in rats. When comparing both groups, the group administered CS-coated nanocapsules showed better activity than the PEG-coated nanocapsules at 6, 10 and 12h after d,l-amphetamine administration. The pharmacokinetic assessment in rats demonstrated that the observed half-lives were free CZP<P80-coated<PEG-coated ̴ CS-coated nanocapsules. Both the P80- and PEG-coated nanocapsules showed a statistically significant increase in their volume of distribution compared to free CZP. On the other hand, the cationic nanocapsules showed a decrease in total clearance. Together, these results indicate that the PEG and CS coatings are a promising delivery system for CZP in the treatment of schizophrenia.

Optimization of Curcuma Oil/Quinine-Loaded Nanocapsules for Malaria Treatment

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(ɛ-caprolactone) or Eudragit® RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 24 factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit® RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78xa0±xa03.60 and 4.76xa0±xa03.46% for F9 and F13, respectively) and highest survival mean time (15.3xa0±xa02.0 and 14.9xa0±xa05.6xa0days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.

Quinine-Loaded Polymeric Nanoparticles: Validation of a simple HPLC-PDA Method to Determine Drug Entrapment and Evaluation of Its Photostability -

Article history: Received on: 01/11/2015 Revised on: 26/11/2015 Accepted on: 22/12/2015 Available online: 27/02/2016 Liquid chromatographic method was developed and validated for quantitative determination of quinine in polymeric nanoparticles. The method was performed using a Waters RP-18 column using a mobile phase consisting of acetonitrile:water:triethylamine (60:40:0.01 v/v/v, and pH aqueous phase adjusted to 3.0 with phosphoric acid). The flow rate was 1.0 mL min -1 and the detection was achieved with a UV-PDA set at 232 nm. The response was linear over a range of 12.0 to 24.0 μg.mL -1 (r = 0.9995). The relative standard deviation values for intra-day and inter-day precision studies were less than 2% and the accuracy was 98.8% to Nc1 and 97.3% to Nc2. The samples free of quinine and quinine-loaded polymeric nanoparticles were subjected to photodegradation conditions. A considerable reduction of degradation of quinine occurred in polymeric nanoparticles. Through these results, it was clear that the nanoencapsulation of quinine protects the drug from degradation by exposure to UV-A light. The analytical method was validated according to International Conference on Harmonization Guidelines and Center for Drug Evaluation and Research.

Educational Activities for Rural and Urban Students to Prevent Skin Cancer in Rio Grande do Sul, Brazil.

BACKGROUNDnExcessive exposure to the sun during childhood is strongly associated with the development of skin cancer in the future. The only way to prevent the development of skin cancer is to protect against ultraviolet radiation, which can be achieved through strategic awareness during childhood and adolescence.nnnOBJECTIVEnThe aim of this work was to evaluate the impact of educational activities for rural and urban students to promote the use of sunscreens and prevent skin cancer.nnnMATERIALS AND METHODSnThis study was carried out with students (9-12 years) of rural (n=70) and urban (n=70) schools in Rio Grande do Sul state, Brazil. The educational interventions were lectures and games. The impact of this strategy was evaluated through the application of a questionnaire before and after the interventions.nnnRESULTSnBefore the intervention, it was found around 50% of rural and urban students were not aware of the damage caused by sun exposure, often exposing themselves to UV radiation without use sunscreen ( ~ 25 %) and at the most critical times of the day/year. After the lectures we observed an improvement in the behavior of the students with regard to sun exposure and knowledge about skin cancer.nnnCONCLUSIONSnThe results of this study emphasize the importance of prevention strategies for skin cancer and promoting the use of sunscreens based educational strategies. The interventions were of great value in relation to disseminating knowledge on the subject.

Co-nanoencapsulation of antimalarial drugs increases their in vitro efficacy against Plasmodium falciparum and decreases their toxicity to Caenorhabditis elegans

&NA; Drugs used for the treatment and prevention of malaria have resistance‐related problems, making them ineffective for monotherapy. If properly associated, many of these antimalarial drugs may find their way back to the treatment regimen. Among the therapeutic arsenal, quinine (QN) is a second‐line treatment for uncomplicated malaria but has side effects that limit its use. Curcumin (CR) is a natural compound with anti‐plasmodial activities and low bioavailability. In this context, the aim of this work was to develop and characterize co‐encapsulated QN+CR‐loaded polysorbate‐coated polymeric nanocapsules (NC‐QC) to evaluate their activity on Plasmodium falciparum and the safety of the nanoformulations for Caenorhabditis elegans. NC‐QC displayed a diameter of approximately 200nm, a negative zeta potential and a slightly basic pH. The drugs are homogeneously distributed in the NCs in the amorphous form. Co‐encapsulated NCs exhibited a significant reduction in P. falciparum parasitemia, better than QN/CR. The worms exposed to NC‐QC showed higher survival and longevity and no decrease in their reproductive capacity compared to free and associated drugs. It was possible to prove that the NCs were absorbed orally by the worms using fluorescence microscopy. Co‐encapsulation of QN and CR was effective against P. falciparum, minimizing the toxic effects caused by chronic exposure of the free drugs in C. elegans. Graphical abstract: Symbol. No Caption available. Highlights:Quinine and curcumin loaded P80‐coated PCL nanocapsules was developed as a strategy against monotherapy‐resistant malaria.Polymeric walls protect quinine and curcumin from ultraviolet‐induced degradation.The co‐encapsulation of quinine and curcumin depicted antimalarial effects on the W2 and 3D7 Plasmodium falciparum strains.Quinine + curcumin‐loaded nanocapsules minimized the toxic effects of free drugs in Caenorhabditis elegans.

Simple HPLC‐UV for the quantification of a new leishmanicidal candidate (E)‐1‐4(trifluoromethyl) benzylidene)‐5‐(2‐4‐dichlorozoyl) carbonylhydrazine (LASSBio‐1736) in rat plasma for pharmacokinetics assessment

In this study, a sensitive HPLC-UV assay was developed and validated for the determination of LASSBio-1736 in rat plasma with sodium diclofenac as internal standard (IS). Liquid-liquid extraction using acetonitrile was employed to extract LASSBio-1736 and IS from 100u2009μL of plasma previously basified with NaOH 0.1u2009M. Chromatographic separation was carried on Waters Spherisorb(®) S5 ODS2 C18 column (150u2009×u20094.6u2009mm, 5u2009μm) using an isocratic mobile phase composed by water with triethylamine 0.3% (pHu20094), methanol and acetonitrile grade (45:15:40, v/v/v) at a flow rate of 1u2009mL/min. Both LASSBio-1736 and IS were eluted at 4.2 and 5u2009min, respectively, with a total run time of 8u2009min only. The lower limit of quantification was 0.2u2009μg/mL and linearity between 0.2 and 4u2009μg/mL was obtained, with an R(2) u2009>xa00.99. The accuracy of the method was >90.5%. The relative standard deviations intra and interday were <6.19 and <7.83%, respectively. The method showed the sensitivity, linearity, precision, accuracy and selectivity required to quantify LASSBio-1736 in preclinical pharmacokinetic studies according to the criteria established by the US Food and Drug Administration and European Medicines Agency. Copyright

Clozapine linked to nanocapsules minimizes tissue and oxidative damage to biomolecules lipids, proteins and DNA in brain of rats Wistar

Clozapine, atypical antipsychotic, can change oxidative stress parameters. It is known that reactive species, in excess, can have a crucial role in the etiology of diseases, as well as, can potentiating adverse effects induce by drugs. The nanocapsules have attracted attention as carriers of several drugs, with consequent reduction of adverse effects. This study aimed to evaluate histopathology and oxidative damage of biomolecules lipids, proteins and DNA in the brain of Wistar rats after treatment with nanocapsules containing clozapine. The study consisted of eight groups of male Wistar rats (nu2009=u20096): saline (SAL), free clozapine (CZP) (25xa0mg/Kg i.p.), blank uncoated nanocapsules (BNC), clozapine-loaded uncoated nanocapsules (CNC) (25xa0mg/Kg i.p.), blank chitosan-coated nanocapsules (BCSN), clozapine-loaded chitosan-coated nanocapsules (CCSN) (25xa0mg/Kg i.p.), blank polyethyleneglycol-coated nanocapsules (BPEGN), clozapine-loaded polyethyleneglycol-coated nanocapsules (CPEGN) (25xa0mg/Kg i.p.). The animals received the formulation once a day for seven consecutive days and euthanized in the eighth day. After euthanasia, the brain was collected and homogenate was processed for further analysis. The histopathology showed less brain tissue damage in nanocapsules-treated groups. The lipid peroxidation and carbonylation of proteins showed a significant increase (pu2009<u20090.05) induced by CZP. CNC and CPEGN groups obtained a reduction membrane of lipids damage and nanocapsules-treated groups showed significant improvement protein damage. CZP was able to induce genetic oxidative damage, while the nanocapsules causing less damage to DNA. The findings show that different coatings can act protecting target tissues decreasing oxidative damage, suggesting that the drug when linked to different nanocapsules is able to mitigate the harmful effects of clozapine.

The efficacy of microemulsion-based delivery to improve vitamin E properties: evaluation of the antinociceptive, antioxidant, antidepressant- and anxiolytic-like activities in mice

A microemulsion‐based delivery system was designed to improve vitamin E (VE) properties, and its antinociceptive, antioxidant, antidepressant‐ and anxiolytic‐like activities in mice were evaluated.