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

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

Benznidazole self-emulsifying delivery system : a novel alternative dosage form for Chagas disease treatment.

Benznidazole (BZ) tablets are a unique form of treatment available for treating Chagas disease. Development of a liquid formulation containing BZ easy to administer orally for the treatment of paediatric patients, particularly for newborns is urgently required, with the same efficacy, safety and suitable biopharmaceutical properties as BZ tablets. Self-emulsifying drug delivery systems (SEDDS) may improve bioavailability of drugs such as BZ, which have poor water solubility and low permeability. In this context, the aim of this work was to develop a liquid BZ-SEDDS formulation as an alternative to tablets and to evaluate its cytotoxicity in different host cell lines and its efficacy in experimental Trypanosoma cruzi infection in mice. The optimized SEDDS formulation (25 mg/ml of BZ) induced no cytotoxicity in H9c2, HepG2 and Caco2 cells in vitro at 25 ?M level. BZ-SEDDS and free-BZ showed similar in vitro trypanocidal activity in H9c2 cells infected by T. cruzi Y strain, with IC50 values of 2.10 ? 0.41 ?M and 1.29 ? 0.01 ?M for BZ and BZ-SEDDS, respectively. A follow up of efficacy in an acute model of infected mice resulted in the same percentage of cure (57%) for both free-BZ and BZ-SEDDS- groups according to established parameters. Furthermore, no additional in vivo toxicity was observed in animals treated with BZ-SEDDS. Taken together, in vitro and in vivo data of BZ-SEDDS showed that the incorporation of BZ into SEDDS does not alter its potency, efficacy and safety. Thus, BZ-SEDDS can be a more practical and personalized orally administered liquid dosage form compared to suspension of crushed BZ-tablets to treat newborn and young children by emulsifying SEDDS in different aqueous liquids with advantage of dosing flexibility

Improved nonclinical pharmacokinetics and biodistribution of a new PPAR pan-agonist and COX inhibitor in nanocapsule formulation.

Wereport the in vitro release profile and comparative pharmacokinetics and biodistribution of a newperoxisome proliferator-activated receptor-? agonist and cyclooxygenase inhibitor (Lyso-7) free or associated to poly(D,Llactic acid) nanocapsules (NC) after intravenous administration in mice. Lyso-7 pertains to the class of insulinsensitizing agents that shows potential beneficial effects in diabetes therapy. Monodispersed Lyso-7 NC with a mean diameter of 273 nm with high encapsulation efficiency (83%) were obtained. Lyso-7 dissolution rate was reduced (2.6-fold) upon loading in NC. The pharmacokinetic parameters were determined using a noncompartmental approach. In comparison with Lyso-7 in solution, the plasma-AUC increased 14-fold, the mean residence time 2.6-fold and the mean half-life (t1/2) 1.5-fold for Lyso-7-NC; the Lyso-7 plasma clearance, distribution volume and elimination rate were reduced 13, 10 and 1.4 fold, respectively, which indicates higher retention of encapsulated Lyso-7 in the blood compartment. Upon association with NC, organ exposure to Lyso-7 was higher in the heart (3.6-fold), lung (2.8-fold), spleen (2.3-fold), kidney (2-fold) and liver (1.8-fold) compared to Lyso-7 in solution. The analysis of whole data clearly indicates that body exposure to Lyso-7 was enhanced and the general toxicity reduced upon nanoencapsulation, allowing further evaluation of Lyso-7 in nonclinical and clinical studie

Polymeric Delivery Systems as a Potential Vaccine against Visceral Leishmaniasis: Formulation Development and Immunogenicity

Recent studies suggest that the association of antigens in microparticles increases the anti-Leishmania vaccine immunogenicity. This study aims to investigate the in situ effect of the adjuvant performance consisting of chitosan-coated poly(D,L-lactic) acid submicrometric particles (SMP) and analyze the inflammatory profile and toxicity. Two formulations were selected, SMP1, containing poly(D,L-lactide) (PLA) 1% wt/v and chitosan 1% wt/v; and SMP2, containing PLA 5% wt/v and chitosan 5% wt/v. After a single dose of the unloaded SMP1 or SMP2 in mice, the SMPs promoted cell recruitment without tissue damage. In addition, besides the myeloperoxidase (MPO) activity having demonstrated similar results among the analyzed groups, a progressive reduction in the levels of N-acetyl-β-D-glucosaminidase (NAG) until 72 h was observed for SMPs. While IL-6 levels were similar among all the analyzed groups along the kinetics, only the SMPs groups had detectable levels of TNF-α. Additionally, the Leishmania braziliensis antigen was encapsulated in SMPs (SMP1Ag and SMP2Ag), and mice were vaccinated with three doses. The immunogenicity analysis by flow cytometry demonstrated a reduction in NK (CD3−CD49+) cells in all the SMPs groups, in addition to impairment in the T cells subsets (CD3+CD4+) and CD3+CD8+) and B cells (CD19+) of the SMP2 group. The resulting data demonstrate that the chitosan-coated SMP formulations stimulate the early events of an innate immune response, suggesting their ability to increase the immunogenicity of co-administered Leishmania antigens