XXV AEDEM International Conference

Comunicação em CongressoEl objetivo de este trabajo es mostrar las principales evoluciones habidas en el modelo ABC desde su aparición en los años ochenta. El ABC multietapas es una evolución natural para su adaptación al entorno real de las organizaciones, el Time-Driven Activity Based Costing - TDABC es un desarrollo que simplifica el ABC al unificar los inductores de coste en la variable tiempo, y finalmente tenemos el modelo Resource Consumption Accounting - RCA que hibrida el ABC con el modelo GPK alemán. Esta ponencia expondrá los tres modelo pero extendiéndose especialmente en el modelo RCA al ser éste el menos conocido y expandido en la práctica de las organizaciones.info:eu-repo/semantics/publishedVersio

Functional polylactide via ring-opening copolymerisation with allyl, benzyl and propargyl glycidyl ethers.

A versatile and simple strategy is presented to synthesize reactive polylactide derivatives and their block copolymers with polyethylene glycol. Commercially available glycidyl ethers with an allyl, benzyl or propargyl functional group were copolymerised with D,L-lactide. Tin(II)-2- ethylhexanoate-catalysis produced polymers with up to 4.6, 5.9 and 2.3 allyl, benzyl or propargyl groups per chain, respectively. In contrast, less than one reactive group per chain was obtained with the organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene. By increasing the polymerisation feed ratio in glycidyl ether polymers with a higher number of reactive groups per chain were obtained, however a decrease in molar mass was observed. An azidocoumarin was conjugated to the propargylated polymers via copper-catalysed azide-alkyne cycloaddition. These dye-labelled polymers produced nanospheres with fluorescent properties and diameters in the 100-nm sizerange, as characterised by asymmetric flow field flow fractionation hyphenated with fluorescence, static and dynamic light scattering detection. The functionalised polymers were obtained at gram-scale in one step from commercially available reagents; therefore providing a robust and easy to implement approach for the production of multifunctional nanomaterials

Nanotecnologia farmacêutica aplicada ao tratamento da malária

In spite of living in a scientific and technological era, malaria continues to be one of the worldwide greatest health challenges. The state-of-the-art policy to keep malaria under control is expected to comprise joint-strategies, such as the vector control, fast diagnosis, therapeutic guarantee, resistance cutback, drug optimization and development of new therapeutic agents and vaccines. Nano and microcarrier systems have been receiving a special attention, including the development of strategies for carrying bioactive agents, vaccines through nanodevices, such as liposomes and nanoparticles, and microdevices, such as microparticles and microemulsions. Numerous nanosystems have already substantiated their effectiveness to optimize vaccines, insecticides, and chemotherapeutic agents applied to the control of malaria. This review is intended to explain the malaria scenario though the world, and to show the nanotechnology as a promising alternative for malaria control and treatment.Apesar do desenvolvimento tecnológico e científico, a malária permanece como um dos maiores problemas de saúde a serem combatidos. As estratégias modernas para o controle da doença prevêem ações conjuntas, como o combate do inseto vetor, diagnóstico rápido e preciso, garantia de terapêutica adequada, redução dos casos de resistência, além do desenvolvimento de novos agentes terapêuticos e vacina e através da otimização da ação de fármacos utilizados na atualidade. Os sistemas de liberação controlada de fármacos vêm recebendo atenção especial nesta área de pesquisa, com o desenvolvimento de estratégias para a veiculação de agentes bioativos e vacinas na forma de nanodispositivos tais como lipossomas, nanopartículas e micropartículas. Diversos nanossistemas já demonstraram eficácia na otimização de vacinas e quimioterápicos destinados ao controle da malária. Este artigo de revisão tem por objetivo avaliar o estado da arte na terapêutica da malária e demonstrar o potencial da nanotecnologia farmacêutica como ferramenta destinada ao combate da doença

Ravuconazole self-emulsifying delivery system : in vitro activity against Trypanosoma cruzi amastigotes and in vivo toxicity.

Self-emulsifying drug delivery systems (SEDDSs) are lipid-based anhydrous formulations composed of an isotropic mixture of oil, surfactant, and cosurfactants usually presented in gelatin capsules. Ravuconazole (Biopharmaceutics Classification System [BCS] Class II) is a poorly water-soluble drug, and a SEDDS type IIIA was designed to deliver it in a predissolved state, improving dissolution in gastrointestinal fluids. After emulsification, the droplets had mean hydrodynamic diameters ,250 nm, zeta potential values in the range of -45 mV to -57 mV, and showed no signs of ravuconazole precipitation. Asymmetric flow field-flow fractionation with dynamic and multiangle laser light scattering was used to characterize these formulations in terms of size distribution and homogeneity. The fractograms obtained at 37?C showed a polydisperse profile for all blank and ravuconazole?SEDDS formulations but no large aggregates. SEDDS increased ravuconazole in vitro dissolution extent and rate (20%) compared to free drug (3%) in 6 h. The in vivo toxicity of blank SEDDS comprising Labrasol? surfactant in different concentrations and preliminary safety tests in repeated-dose oral administration (20 days) showed a dose-dependent Labrasol toxicity in healthy mice. Ravuconazole?SEDDS at low surfactant content (10%, v/v) in Trypanosoma cruzi-infected mice was safe during the 20-day treatment. The anti-T. cruzi activity of free ravuconazole, ravuconazole?SEDDS and each excipient were evaluated in vitro at equivalent ravuconazole concentrations needed to inhibit 50% or 90% (IC50 and IC90), respectively of the intracellular amastigote form of the parasite in a cardiomyocyte cell line. The results showed a clear improvement of the ravuconazole anti-T. cruzi activity when associated with SEDDS. Based on our results, the repurposing of ravuconazole in SEDDS dosage form is a strategy that deserves further in vivo investigation in preclinical studies for the treatment of human T. cruzi infections

Polymeric nanocapsules prevent oxidation of core-loaded molecules: evidence based on the effects of docosahexaenoic acid and neuroprostane on breast cancer cells proliferation

International audienceBackground:Nanocapsules, as a delivery system, are able to target drugs and other biologically sensitive moleculesto specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs frominactivation upon interaction with the body and to ensure the release to the target. However, the mechanism ofimproved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellularlevels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidityand mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it hasbeen suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidantagents Methods:The effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative mediumwas evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and ofthe non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions. Results:DHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) andenhanced by the pro-oxidant hydrogen peroxide that confirmsthat DHA has to be oxidized to exert its anti-proliferativeproperties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F4t-neuroprostane, a bioactive, non-enzymaticoxygenated metabolite of DHA known to play a major role inthe prevention of cardiovascular diseases. DHA-loadednanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H2O2maintainedthe inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of4(RS)-4-F4t-neuroprostane that is more hydrophilic than DHA. Conclusion:Overall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites.They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not thesole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability,and control the release of bioactive fatty acids following their lipophilicities

Uso de antimicrobiano nanoparticulado para o tratamento da mastite subcl?nica de ovelhas de corte no per?odo seco.

A inflama??o da gl?ndula mam?ria ? uma das principais causas de preju?zo na ovinocultura. Este estudo teve como objetivo investigar as taxas de cura do tratamento da mastite subcl?nica ap?s infus?o intramam?ria de princ?pio ativo antimicrobiano no momento da secagem, em formula??es convencional e nanoparticulada. Os rebanhos estavam localizados em S?o Carlos, S?o Paulo, Brasil. Analisou-se um total de 584 gl?ndulas mam?rias de 307 ovelhas de aptid?o para produ??o de carne. Triagem pr?via dos casos subcl?nicos de mastite foi efetuada por meio do California Mastitis Test (CMT) e/ou da contagem de c?lulas som?ticas (CCS). An?lises microbiol?gicas foram realizadas para confirma??o da etiologia infecciosa. As gl?ndulas mam?rias com mastite subcl?nica foram distribu?das em tr?s grupos: G1 (Controle; gl?ndulas mam?rias que n?o receberam tratamento antimicrobiano); G2 (gl?ndulas mam?rias em que foi administrado 100 mg de cloxacilina benzatina em estrutura convencional) e G3 (gl?ndulas mam?rias em que foi administrado 50 mg de cloxacilina benzatina em estrutura nanoencapsulada). O tratamento aplicado ao G3 mostrou-se mais eficiente (P=0,047) na cura de gl?ndulas mam?rias com mastite subcl?nica. O uso da cloxacilina nanoencapsulada no momento da secagem de ovelhas de corte auxilia no controle da mastite subcl?nica infecciosa e reduz os preju?zos consequentes.Inflammation of the mammary gland is one of the main causes of losses in sheep-rearing. This study aimed to investigate the cure rates from treating subclinical mastitis after intramammary infusion of active antimicrobial agents as conventional formulations or as nanoparticles, at the time when the ewes are being dried off. A total of 584 mammary glands in 307 ewes in meat-producing herds located in S?o Carlos, S?o Paulo, Brazil, were analyzed. Prescreening of subclinical mastitis cases was done using the California mastitis test (CMT) and/or the somatic cell count (SCC). Microbiological analyses were performed to confirm the infectious etiology. The mammary glands with subclinical mastitis were distributed into three groups: G1 (control; mammary glands that did not receive any antimicrobial treatment); G2 (mammary glands to which 100mg of benzathine cloxacillin in conventional form were administered); and G3 (mammary glands to which 50mg of benzathine cloxacillin in nanoparticulate form were administered). The treatment applied to G3 was more efficient (P=0.047) in curing mammary glands with subclinical mastitis. Use of cloxacillin nanoparticles at the time when the ewes are being dried off helps to control infectious subclinical mastitis and reduces consequential losses among meat-producing herds

Cloxacillin nanostructured formulation for the treatment of bovine keratoconjunctivitis.

Infectious bovine keratoconjunctivitis (IBK) is a widespread, contagious ocular disease that affects cattle, especially dairy breeds. The disease is caused by Gram-negative bacteria mainly Moraxella bovis, and its treatment consists of parenteral or topic antibiotic therapy. The topic treatment approach is used more commonly in lactating cows, to avoid milk disposal. However, treatment failures are common, because the antibiotic is removed during lacrimation. This study aimed to evaluate the susceptibility of commercial cloxacillin and evaluate the efficacy of nanostructured cloxacillin in clinical cases of IBK by Moraxella. The minimum inhibitory concentration (MIC) of nanoparticle cloxacillin nanocoated, the nanoparticle without the antibiotic and the commercial cloxacillin were determined in vitro with field samples of Moraxella ovis (5) and Moraxella bovis (5). The efficiency of nanoparticles was tested in three cows naturally infected that were treated with 1.0 mL (with 0.32 mg of nanostructured cloxacillin) for the ocular route. Moraxella bovis was isolated and identified by biochemical and molecular methods before the treatment. The animals were treated every 12 h for six days. The cure was considered by the absence of clinical symptoms and bacteria after treatment. The mucoadhesive nanoparticle-based formulation promoted clinical cure with a low number of doses of antibiotics, probably due to the maintenance of the MIC in the ocular mucosa for longer due to the mucoadhesive characteristics of the nanoparticle. The results indicate that the use of nanocoated cloxacillin is possible to control infectious bovine keratoconjunctivitis

Impact of dose and surface features on plasmatic and liver concentrations of biodegradable polymeric nanocapsules.

The effect of polymeric nanocapsule dose on plasmatic and liver concentrations 20 min after intravenous administration in mice was evaluated. Nanocapsules were prepared with different polymers, namely, poly(D,Llactide) (PLA), polyethylene glycol-block-poly(D,L-lactide) (PLA-PEG), and PLA with chitosan (PLA-Cs) and compared with a nanoemulsion. These formulations were labelled with a phthalocyanine dye for fluorescent detection. The nanostructures had narrow size distributions upon separation by asymmetric flow field flow fractionation with static and dynamic light scattering detection, with average hydrodynamic diameters in the 130?300 nm range, negative zeta potentials, except PLA-Cs nanocapsules, which had a positive zeta potential. Flow cytometry revealed uptake mostly by monocytes and neutrophils in mice and human blood. PLA nanocapsules and the nanoemulsion showed dose-dependent plasma concentrations, where the percentage of plasmatic fluorescence increased with increasing administered dose. In contrast, PLA-PEG nanocapsules led to a dose-independent plasmatic profile. PLA-Cs nanocapsules showed the lowest plasmatic and liver levels of fluorescence at all administered doses and significant intravenous toxicity in mice. This work demonstrates the importance of considering the nanocarrier dose when evaluating pharmacokinetic and biodistribution data and emphasizes the role of surface features in determining the plasmatic and liver concentrations of a poorly soluble lipophilic encapsulated compound