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Lipid-Polymer Membranes as Carriers for L-Tryptophan: Molecular and Metabolic Properties

Open Journal of Medicinal Chemistry 2013年第1期3卷 31-39页

作者： Fernández Ruocco María Julieta Siri Macarena Igartúa Daniela Prieto María Jimena Alonso silvia Del Valle chiaramoni nadia silvia Instituto Multidisciplinario de Biología Celular Consejo Nacional de Investigaciones Científicas y Técnicas Buenos Aires Argentina Laboratory of Biomembranes Department of Science and Technology Universidad Nacional de Quilmes Buenos Aires Argentina

Polymerized liposomes encapsulating L-tryptophan were studied with the aim to characterize them as drug delivery systems for the treatment of several metabolic diseases that need an increased systemic L-tryptophan concentration. polymerized liposomes were obtained by UV irradiation of vesicles containing 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in a 1:1 molar ratio, in the presence of 10 and 50 mol% of L-tryptophan (respect to total lipid concentration). Polymerization efficiency was studied spectrophotometrically. Also, bilayer packing at the polar head region was followed with the Merocyanine 540 (MC540) and specific interactions in the lipopolymers were studied by FTIR. High L-tryptophan concentrations (50 mol% respect to total lipid concentration) induced a higher amount of six- and nine-unit polymers. This phenomenon was induced because the L-tryptophan located outside the lipid membrane was included in it during the polymerization process and was thus responsible for the better accommodate of the polar head region. This was not possible with the lower amount of L-tryptophan (10 mol%). The stability of lipopolymers with different amounts of L-tryptophan was studied through release profiles. Polymerized liposomes with 50 mol% of L-tryptophan were able to retain around 80% of the amino acid after 24 hours, whereas those with 10 mol % of the amino acid were able to retain 20%. The metabolic activity of the Caco-2 cell line was also studied. Cytotoxic effects were low in the presence of polymerized liposomes, rendering a maximum percentage of cell death of 30%. In summary, this work stresses the relevance of nonspecific drug-polymerized membrane binding on L-tryptophan pharmacological interaction with possible pharmaceutical applications in liposomal drug delivery. Moreover, the absence of significant cytotoxic effects allows the system proposed to be applied in human health.

关键词： Lipopolymers L-Tryptophan Drug Delivery

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Effect of Risperidone and Fluoxetine on the Movement and Neurochemical Changes of Zebrafish

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Open Journal of Medicinal Chemistry 2012年第4期2卷 129-138页

作者： Maria Jimena Prieto Hector Carreno Gutierrez Rosario Arévalo Arévalo nadia S. chiaramoni silvia del Valle Alonso Biomembrane Laboratory Department of Science and Technology National University of Quilmes Buenos Aires Argentina Department of Cell Biology and Pathology Institute of Neuroscience of Castilla y Leon School of Medicine University of Salamanca Salamanca Spain IMBICE-CONICET Buenos Aires Argentina

Brain developmental disorders in humans, including Autism Spectrum Disorders (ASD) and Down’s syndrome, have been linked to increased serotonin levels. This work was designed to study changes in serotonin levels in the early stages of development with two classes of antipsychotic drugs: Risperidone, a drug that blocks serotonin and dopamine receptors, and fluoxetine, a serotonin reuptake inhibitor. The use of antipsychotic drugs is a solid choice to study the decrease and increase of these neurotransmitters and their influence on development. The study of these parameters will give an idea of the effects of serotonin in early developmental stages. To this end, we examined the effects of risperidone and fluoxetine on the locomotor activity, heart rate and brain development of zebrafish larvae. Our results showed that in larvae exposed to fluoxetine alone, swimming was significantly increased at 9 dpf (days post-fertilization). Erratic and abnormal movements were observed suggesting a toxic effect of fluoxetine. No erratic swimming was observed in larvae treated with fluoxetine plus risperidone. Both drugs presented morphological changes in dopaminergic neurons and mononeurons. Exposure to fluoxetine plus risperidone indicated possible reversal effects. Studies in zebrafish allow obtaining new insights into the side effects of these drugs as well as into the brain control of locomotor activity. Testing several drug-induced changes in behavior and serotonin levels is one of the experimental approaches for screening a new therapeutically relevant compound, and thus, merits further research.

关键词： Zebrafish Risperidone Fluoxetine Serotonin Behavioral

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