Liposomes as Matrices to Hold Bioactive Compounds for Drinkable Foods: Their Ability to Improve Health and Future Prospects

The aim of this chapter is to describe the use of bioactive compounds with beneficial effects on human health beyond their basic nutritional value. Bioactive compounds like vitamin E, vitamin C, and fatty acids (omega-3 and omega-6) have an important nutritional contribution and are related to the prevention of certain diseases with global impact such as cancer. However, the addition of vitamins in a food product is not easy: E is destroyed by UV-light, and C is dramatically reduced during heat processes. The use of liposomes as matrices to hold bioactive compounds appears to be a promising solution. Liposomes were made of natural soybean lecithin, which has a great nutritional importance, and more so combined with stearic acid or calcium stearate (CaS). Thus, this stabilize liposomes and contribute to the stability of bioactive compounds and to preserve their activity. The stability of bioactive compounds/liposomes incorporated into aqueous food must be demonstrated in properties such as oxidative tendency, morphology, size, and membrane packaging after heat treatment processes. But to make a product applicable at the commercial level, its texture and mouthfeel arising from the ingestion of drinkable foods are all-important to consumer’s choice and sensory acceptability must not undergo any modification

G4.5 Pamam Dendrimer-Risperidone: Biodistribution and Behavioral Changes in In Vivo Model

Dendritic polymers are considered as emerging and outstanding carriers as modern medicinal systems due to their derivatisable branched architecture and possibility to modify them in numerous ways. Here, G4.5 PAMAM dendrimers were obtained as carriers of the antipsychotic drug risperidone. Despite their extensive applicability in the pharmaceutical field, the use of dendrimers as carriers in biological systems is constrained due to their inherent associated toxicity. The biocompatibility of dendrimers and dendrimer-risperidone complexes was evaluated in vivo for biological performance. To this end, the pharmacokinetics and biodistribution after oral treatment of free risperidone and dendrimer-risperidone complexes were studied in healthy mice. Also, the behavioral changes such as locomotion, aggression, dominance in male and female mice were evaluated both after a single dose and after daily therapy for 8 days. Also, in vivo effects of risperidone and dendrimer-risperidone complexes on the locomotion of zebrafish larvae were explored. The data obtained suggest that the unmetabolized risperidone complexes increase the arrival to the brain after 90 minutes. On the other hand, behavioral studies showed an increase in the potency of the drug in animals treated with the complexesFil: Prieto, Maria Jimena. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: del Rio Zabala, Nahuel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Marotta, Cristian Hernán. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Bichara, Darío Román. Fundación Instituto Leloir; ArgentinaFil: Simonetta, Sergio Hernan. Fundación Instituto Leloir; ArgentinaFil: Chiaramoni, Nadia Silvia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Alonso, Silvia del Valle. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentin

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

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.Instituto Multidisciplinario de Biología Celula

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

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.Instituto Multidisciplinario de Biología Celula

Lipid-polymer membranes as carriers for L-tryptophan : Molecular and metabolic properties

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.Instituto Multidisciplinario de Biología Celula

Lipid-polymer membranes as carriers for L-tryptophan : Molecular and metabolic properties

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.Instituto Multidisciplinario de Biología Celula

G4.5 Pamam Dendrimer-Risperidone: Biodistribution and Behavioral Changes in In Vivo Model

Dendritic polymers are considered as emerging and outstanding carriers as modern medicinal systems due to their derivatisable branched architecture and possibility to modify them in numerous ways. Here, G4.5 PAMAM dendrimers were obtained as carriers of the antipsychotic drug risperidone. Despite their extensive applicability in the pharmaceutical field, the use of dendrimers as carriers in biological systems is constrained due to their inherent associated toxicity. The biocompatibility of dendrimers and dendrimer-risperidone complexes was evaluated in vivo for biological performance. To this end, the pharmacokinetics and biodistribution after oral treatment of free risperidone and dendrimer-risperidone complexes were studied in healthy mice. Also, the behavioral changes such as locomotion, aggression, dominance in male and female mice were evaluated both after a single dose and after daily therapy for 8 days. Also, in vivo effects of risperidone and dendrimer-risperidone complexes on the locomotion of zebrafish larvae were explored. The data obtained suggest that the unmetabolized risperidone complexes increase the arrival to the brain after 90 minutes. On the other hand, behavioral studies showed an increase in the potency of the drug in animals treated with the complexesInstituto Multidisciplinario de Biología Celula

Optimization and in vivo toxicity evaluation of G4.5 PAMAM dendrimer-risperidone complexes

Risperidone is an approved antipsychotic drug belonging to the chemical class of benzisoxazole. This drug has low solubility in aqueous medium and poor bioavailability due to extensive first-pass metabolism and high protein binding (.90%). Since new strategies to improve efficient treatments are needed, we studied the efficiency of anionic G4.5 PAMAM dendrimers as nanocarriers for this therapeutic drug. To this end, we explored dendrimer-risperidone complexation dependence onsolvent concentration, pH and molar relationship. The best dendrimer-risperidone incorporation (46 risperidone molecules per dendrimer) was achieved with a mixture of chloroform:methanol 50:50 v/v solution pH 3. In addition, to explore the possible effects of this complex,in vivo studies were carried out in the zebrafish model. Changes in the development of dopaminergic neurons and motoneurons were studied using tyrosine hydroxylase and calretinin, respectively. Physiologicalchanges were studied through histological sections stained with hematoxylin-eosin to observe possible morphological brain changes. The most significant changes were observed when larvae were treated with free risperidone, and no changes were observed when larvae were treated with the complex.Fil: Prieto, Maria Jimena. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: del Rio Zabala, Nahuel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Marotta, Cristian Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Carreño Gutierrez, Hector. Universidad de Salamanca; EspañaFil: Arevalo Arevalo, Rosario. Universidad de Salamanca; EspañaFil: Chiaramoni, Nadia Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Alonso, Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentin

G4.5 Pamam Dendrimer-Risperidone: Biodistribution and Behavioral Changes in In Vivo Model

Dendritic polymers are considered as emerging and outstanding carriers as modern medicinal systems due to their derivatisable branched architecture and possibility to modify them in numerous ways. Here, G4.5 PAMAM dendrimers were obtained as carriers of the antipsychotic drug risperidone. Despite their extensive applicability in the pharmaceutical field, the use of dendrimers as carriers in biological systems is constrained due to their inherent associated toxicity. The biocompatibility of dendrimers and dendrimer-risperidone complexes was evaluated in vivo for biological performance. To this end, the pharmacokinetics and biodistribution after oral treatment of free risperidone and dendrimer-risperidone complexes were studied in healthy mice. Also, the behavioral changes such as locomotion, aggression, dominance in male and female mice were evaluated both after a single dose and after daily therapy for 8 days. Also, in vivo effects of risperidone and dendrimer-risperidone complexes on the locomotion of zebrafish larvae were explored. The data obtained suggest that the unmetabolized risperidone complexes increase the arrival to the brain after 90 minutes. On the other hand, behavioral studies showed an increase in the potency of the drug in animals treated with the complexesInstituto Multidisciplinario de Biología Celula