Multifunctional emulsion for potential wound-healing applications: A development for co-administration of essential vitamins, silver nanoparticles, and potent active ingredients

This research explores the formulation of novel oil-in-water emulsion designed for the co-delivery of compounds with different properties that jointly represent an exceptional system to apply in skin regeneration, such as essential vitamins A and E, silver nanoparticles, silver sulfadiazine, and lidocaine. First, the preparation method of emulsions was optimized, characterizing their stability over storage time. Emulsions, which were prepared with certain stirring speed and time, presented the lower droplet size and the higher stability for 28 days. Second, the active ingredients were incorporated into the optimized emulsion, and their stability and antimicrobial capacity were evaluated. In addition to being a stable colloidal system, the emulsion with active ingredients demonstrated antimicrobial effects against Pseudomonas aeruginosa and Staphylococcus aureus (both usually present in skin wounds). The antimicrobial properties of silver nanoparticles and the healing-promoting characteristics of vitamins make this combination promising for applications in pharmaceutical and cosmetic formulations. Utilizing natural oils and biocompatible components aligns with sustainable and health-conscious product development trends. The findings of this study hold implications for diverse applications in medicine and cosmetics.Fil: Sosa, Ayelen Morena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Ingeniería en Alimentos; ArgentinaFil: Martínez, Luis M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Alonso, Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Prieto, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Martinez, Carolina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología - Universidad Nacional de Quilmes - GBEyB; Argentin

Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA

Different viral and non-viral vectors have been designed to allow the delivery of nucleic acids in gene therapy. In general, non-viral vectors have been associated with increased safety for in vivo use; however, issues regarding their efficacy, toxicity and stability continue to drive further research. Thus, the aim of this study was to evaluate the potential use of the polymerizable diacetylenic lipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) as a strategy to formulate stable cationic lipopolymers in the delivery and protection of plasmid DNA. Cationic lipopolymers were prepared following two different methodologies by using DC8,9PC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and the cationic lipids (CL) 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), stearylamine (SA), and myristoylcholine chloride (MCL), in a molar ratio of 1:1:0.2 (DMPC:DC8,9PC:CL). The copolymerization methodology allowed obtaining cationic lipopolymers which were smaller in size than those obtained by the cationic addition methodology although both techniques presented high size stability over a 166-day incubation period at 4C. Cationic lipopolymers containing DOTAP or MCL were more efficient in complexing DNA than those containing SA. Moreover, lipopolymers containing DOTAP were found to form highly stable complexes with DNA, able to resist serum DNAses degradation. Furthermore, neither of the cationic lipopolymers (with or without DNA) induced red blood cell hemolysis, although metabolic activity determined on the L-929 and Vero cell lines was found to be dependent on the cell line, the formulation and the presence of DNA. The high stability and DNA protection capacity as well as the reduced toxicity determined for the cationic lipopolymer containing DOTAP highlight the potential advantage of using lipopolymers when designing novel nonviral carrier systems for use in in vivo gene therapy. Thus, this work represents the first steps toward developing a cationic lipopolymer-based gene delivery system using polymerizable and cationic lipids.Instituto Multidisciplinario de Biología Celula

Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA

Different viral and non-viral vectors have been designed to allow the delivery of nucleic acids in gene therapy. In general, non-viral vectors have been associated with increased safety for in vivo use; however, issues regarding their efficacy, toxicity and stability continue to drive further research. Thus, the aim of this study was to evaluate the potential use of the polymerizable diacetylenic lipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) as a strategy to formulate stable cationic lipopolymers in the delivery and protection of plasmid DNA. Cationic lipopolymers were prepared following two different methodologies by using DC8,9PC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and the cationic lipids (CL) 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), stearylamine (SA), and myristoylcholine chloride (MCL), in a molar ratio of 1:1:0.2 (DMPC:DC8,9PC:CL). The copolymerization methodology allowed obtaining cationic lipopolymers which were smaller in size than those obtained by the cationic addition methodology although both techniques presented high size stability over a 166-day incubation period at 4C. Cationic lipopolymers containing DOTAP or MCL were more efficient in complexing DNA than those containing SA. Moreover, lipopolymers containing DOTAP were found to form highly stable complexes with DNA, able to resist serum DNAses degradation. Furthermore, neither of the cationic lipopolymers (with or without DNA) induced red blood cell hemolysis, although metabolic activity determined on the L-929 and Vero cell lines was found to be dependent on the cell line, the formulation and the presence of DNA. The high stability and DNA protection capacity as well as the reduced toxicity determined for the cationic lipopolymer containing DOTAP highlight the potential advantage of using lipopolymers when designing novel nonviral carrier systems for use in in vivo gene therapy. Thus, this work represents the first steps toward developing a cationic lipopolymer-based gene delivery system using polymerizable and cationic lipids.Instituto Multidisciplinario de Biología Celula

Dibucaine in Ionic-Gradient Liposomes: Biophysical, Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of dibucaine.Fil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Prieto, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Feas, Daniela Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Ribeiro, Lígia N.M.. Universidade Estadual de Campinas; BrasilFil: Silva, Camila M.G.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Guilherme, Viviane A.. Universidade Estadual de Campinas; BrasilFil: Dantzger, Darlene D.. Universidade Estadual de Campinas; BrasilFil: Machado, Daisy. Universidade Estadual de Campinas; BrasilFil: Alonso, Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

Functional hybrid nanoemulsions for sumatriptan intranasal delivery

In recent years, advanced nanohybrid materials processed as pharmaceuticals have proved to be very advantageous. Triptans, such as the commercially available intranasal sumatriptan (SMT), are drugs employed in the treatment of painful migraine symptoms. However, SMT effectiveness by the intranasal route is limited by its high hydrophilicity and poor mucoadhesion. Therefore, we designed hybrid nanoemulsions (NE) composed of copaiba oil as the organic component plus biopolymers (xanthan, pectin, alginate) solubilized in the continuous aqueous phase, aiming at the intranasal release of SMT (2% w/v). Firstly, drug-biopolymer complexes were optimized in order to decrease the hydrophilicity of SMT. The resultant complexes were further encapsulated in copaiba oil-based nanoparticles, forming NE formulations. Characterization by FTIR-ATR, DSC, and TEM techniques exposed details of the molecular arrangement of the hybrid systems. Long-term stability of the hybrid NE at 25°C was confirmed over a year, regarding size (~ 120 nm), polydispersity (~ 0.2), zeta potential (~ −25 mV), and nanoparticle concentration (~ 2.1014 particles/mL). SMT encapsulation efficiency in the formulations ranged between 41–69%, extending the in vitro release time of SMT from 5 h (free drug) to more than 24 h. The alginate-based NE was selected as the most desirable system and its in vivo nanotoxicity was evaluated in a zebrafish model. Hybrid NE treatment did not affect spontaneous movement or induce morphological changes in zebrafish larvae, and there was no evidence of mortality or cardiotoxicity after 48 h of treatment. With these results, we propose alginate-based nanoemulsions as a potential treatment for migraine pain.Fil: Ribeiro, Lígia N. M.. Universidade Estadual de Campinas; BrasilFil: Rodrigues da Silva, Gustavo H.. Universidade Estadual de Campinas; BrasilFil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Breitkreitz, Márcia C.. Universidade Estadual de Campinas; BrasilFil: Martinez, Carolina Soledad. 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; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Prieto, Maria Jimena. Universidad Nacional de Quilmes; 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: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

Diacetylenic lipids in the design of stable lipopolymers able to complex and protect plasmid DNA

Different viral and non-viral vectors have been designed to allow the delivery of nucleic acids in gene therapy. In general, non-viral vectors have been associated with increased safety for in vivo use; however, issues regarding their efficacy, toxicity and stability continue to drive further research. Thus, the aim of this study was to evaluate the potential use of the polymerizable diacetylenic lipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) as a strategy to formulate stable cationic lipopolymers in the delivery and protection of plasmid DNA. Cationic lipopolymers were prepared following two different methodologies by using DC8,9PC, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and the cationic lipids (CL) 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), stearylamine (SA), and myristoylcholine chloride (MCL), in a molar ratio of 1:1:0.2 (DMPC:DC8,9PC:CL). The copolymerization methodology allowed obtaining cationic lipopolymers which were smaller in size than those obtained by the cationic addition methodology although both techniques presented high size stability over a 166-day incubation period at 4C. Cationic lipopolymers containing DOTAP or MCL were more efficient in complexing DNA than those containing SA. Moreover, lipopolymers containing DOTAP were found to form highly stable complexes with DNA, able to resist serum DNAses degradation. Furthermore, neither of the cationic lipopolymers (with or without DNA) induced red blood cell hemolysis, although metabolic activity determined on the L-929 and Vero cell lines was found to be dependent on the cell line, the formulation and the presence of DNA. The high stability and DNA protection capacity as well as the reduced toxicity determined for the cationic lipopolymer containing DOTAP highlight the potential advantage of using lipopolymers when designing novel nonviral carrier systems for use in in vivo gene therapy. Thus, this work represents the first steps toward developing a cationic lipopolymer-based gene delivery system using polymerizable and cationic lipids.Instituto Multidisciplinario de Biología Celula

Rendimiento de cultivares de arveja (Pisum sativum, L) en diferentes ambientes de la República Argentina - Campaña 2018-2019

Se estima que la población mundial para 2050 llegará a las 9.000 millones de personas, por lo que la demanda de alimentos será creciente y las legumbres juegan un papel fundamental en la dieta de los países que más población tienen, como India y China. Dentro de las legumbres, arveja es la especie de menor precio en relación a lenteja, garbanzo o porotos. En este sentido, cuando se hace necesario importar alimentos, las arvejas son las preferidas. El área de siembra de arveja en Argentina no se ha incrementado, en gran parte por el bajo precio en 2018 en relación a otros cultivos de invierno y, por otro lado, por el escaso o nulo consumo interno (Vita y Prieto, 2018). Sin embargo, dado los precios actuales de arveja verde (alrededor de 250 U$S/tn), hacen mucho más interesante la posibilidad de incluirla en los sistemas de producción. Sumado al beneficio del margen de los planteos agrícolas, una vía de uso diferente a la exportación o al consumo humano directo, es su inclusión en las dietas forrajeras destinadas a alimentar bovinos de carne o de leche, como así también porcinos o aves. Abundan en la bibliografía internacional los trabajos donde se demuestra que el uso de arveja en reemplazo parcial de otras harinas proteicas, como la de soja y fuentes energéticas como el maíz, conducen a ganancias de peso similares o superiores a los testigos (Lardy et al, 2009; Fendrick et al, 2005; Soto Navarro et al, 2012; Pasinato et al, 2019; Landblom & Poland, 1997; Reed et al, 2004; Birkelo et al, 2000). Por todo esto, es importante conocer la adaptación de los diferentes materiales disponibles en el mercado a los ambientes productivos de Argentina.EEA PergaminoFil: Prieto, Gabriel María. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros. Agencia de Extensión Rural Arroyo Seco; ArgentinaFil: Appella, Cristian Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Chacra Experimental Integrada Barrow; ArgentinaFil: Avila, F. CREA. Consorcio Regional de Experimentación Agrícola; ArgentinaFil: Bracco, V. Universidad Nacional del Noroeste de la Provincia de Buenos Aires (UNNOBA). Sede Junín; ArgentinaFil: Brassesco, Raul Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Paraná. Agencia de Extensión Rural Victoria; ArgentinaFil: Buschittari, D. Agricultores Federados Argentinos (AFA). Sociedad Cooperativa Limitada (SCL); ArgentinaFil: Casciani, Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros. Agencia de Extensión Rural Arroyo Seco; ArgentinaFil: Espósito, María Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Oliveros; ArgentinaFil: Fariña, Leandro. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Agencia Regional de Desarrollo Productivo; ArgentinaFil: Fekete, Ana Cecilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Frolla, Franco Daniel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bordenave; ArgentinaFil: Gallego, Juan José. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior de Río Negro; ArgentinaFil: Introna, Jimena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Sección Agronomía; ArgentinaFil: Lavilla, M. Universidad Nacional del Noroeste de la Provincia de Buenos Aires (UNNOBA). Sede Junín; ArgentinaFil: Maggio, J.C. Agrar del Sur; ArgentinaFil: Prece, Natalia María. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Sección Agronomía; ArgentinaFil: Maggio, María Elisa. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Mariotti Martinez, Jorge Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Martinez, S. Universidad Nacional del Noroeste de la Provincia de Buenos Aires (UNNOBA). Sede Junín; ArgentinaFil: Orliacq, A. Ministerio de Agroindustria de la Provincia de Buenos Aires. Chacra Experimental Pasman; ArgentinaFil: Vallejo, Maximiliano. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Paraná. Agencia de Extensión Rural Victoria; ArgentinaFil: Zgrablich, A. Universidad Nacional de Córdoba (UNC); Argentin

PAMAM dendrimers of generation 4.5 loaded with curcumin interfere with α-synuclein aggregation

Curcumin (CUR) is a bioactive compound that has been proposed for the treatment of various neurodegenerative diseases. However, its use is limited due to its low solubility in aqueous media and chemical instability under physiological conditions. Herein, we propose a strategy to overcome these limitations by using PAMAM dendrimers of generation 4.5 (DG4.5). Using a combination of biophysical techniques together with in vitro models, we demonstrate that CUR-DG4.5 complexes: (i) increased the solubility and stability of CUR via internalization into dendrimer's pockets and interaction with terminal carboxylic groups; (ii) showed in vitro biocompatibility and increased CUR uptake; (iii) presented DPPH radical scavenging activity and in vitro inhibition of H2O2-induced stress; and (iv) interfere with α-synuclein aggregation. In conclusion, this work lays the foundation to use curcumin-loaded PAMAM dendrimers of generation 4.5 as nanodrugs capable of reducing oxidative stress and inhibiting α-synuclein aggregation to treat synucleinopathies

Light-scattering measurements.

<p>Light-scattering measurements.</p