Sistemas de vehiculización del antitumoral violaceína para uso terapéutico

En el presente trabajo se detallan los resultados obtenidos fruto de la investigación para la vehiculización del pigmento de origen bacteriano violaceína, con el objetivo de crear sistemas terapéuticos antitumorales. La sección siguiente constituye una breve introducción al campo de aplicación de estos sistemas (el cáncer), así como información específica del funcionamiento de la violaceína, las problemáticas asociadas a su administración y una descripción general de los sistemas de vehiculización empleados. La sección 3, contiene los objetivos de esta tesis. En la sección 4, se describe un sistema pH-responsivo basado en los biopolímeros pectina y gelatina, con el objetivo de lograr una administración oral y una liberación del fármaco en colon. En la sección 5, se muestra un sistema basado en nanopartículas lipídicas en el que se buscó obtener un direccionamiento activo hacia células que sobre expresen receptores de folato. En la sección 6, se presenta un sistema con el objetivo de ser implantado, basado tanto en nanopartículas lipídicas como en biopolímeros, con dos adiciones; una enzima activa, con el doble propósito de actuar de manera terapéutica pero también estimular la liberación de violaceína y que el sistema se ha diseñado como una tinta para impresión 3D. En la sección 7 se ofrecen las conclusiones finales respecto de los capítulos anteriores y las secciones 8, 9 y 10 contienen la Bibliografía, las abreviaturas y una tabla de figuras respectivamente.Facultad de Ciencias Exacta

Bacterial Cellulose-Based Materials as Dressings for Wound Healing

Bacterial cellulose (BC) is produced by several microorganisms as extracellular structures and can be modified by various physicochemical and biological strategies to produce different cellulosic formats. The main advantages of BC for biomedical applications can be summarized thus: easy moldability, purification, and scalability; high biocompatibility; and straightforward tailoring. The presence of a high amount of free hydroxyl residues, linked with water and nanoporous morphology, makes BC polymer an ideal candidate for wound healing. In this frame, acute and chronic wounds, associated with prevalent pathologies, were addressed to find adequate therapeutic strategies. Hence, the main characteristics of different BC structures—such as membranes and films, fibrous and spheroidal, nanocrystals and nanofibers, and different BC blends, as well as recent advances in BC composites with alginate, collagen, chitosan, silk sericin, and some miscellaneous blends—are reported in detail. Moreover, the development of novel antimicrobial BC and drug delivery systems are discussed.Fil: Horue, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Silva, Jhonatan Miguel. University Of Araraquara; BrasilFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Brandão, Larissa Reis. University Of Araraquara; BrasilFil: Barud, Hernane da Silva. University Of Araraquara; BrasilFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Centro de Estudios Interdisciplinarios. Laboratorio Max Planck de Biología Estructural, Química y Biofísica Molecular de Rosario; . Universidad Federal Do Abc; Brasi

Trypanosomatid-caused conditions: State of the art of therapeutics and potential applications of lipid-based nanocarriers

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease, and leishmaniasis) are neglected tropical infectious diseases that mainly affect socioeconomically vulnerable populations. The available therapeutics display substantial limitations, among them limited efficacy, safety issues, drug resistance, and, in some cases, inconvenient routes of administration, which made the scenarios with insufficient health infrastructure settings inconvenient. Pharmaceutical nanocarriers may provide solutions to some of these obstacles, improving the efficacy–safety balance and tolerability to therapeutic interventions. Here, we overview the state of the art of therapeutics for trypanosomatid-caused diseases (including approved drugs and drugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriers encapsulating approved and non-approved drugs for these diseases. Numerous studies have focused on the obtention and preclinical assessment of lipid nanocarriers, particularly those addressing the two currently most challenging trypanosomatid-caused diseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studies suggest that delivering the drugs using such type of nanocarriers could improve the efficacy–safety balance, diminishing cytotoxicity and organ toxicity, especially in leishmaniasis. This constitutes a very relevant outcome, as it opens the possibility to extended treatment regimens and improved compliance. Despite these advances, last-generation nanosystems, such as targeted nanocarriers and hybrid systems, have still not been extensively explored in the field of trypanosomatid-caused conditions and represent promising opportunities for future developments. The potential use of nanotechnology in extended, well-tolerated drug regimens is particularly interesting in the light of recent descriptions of quiescent/dormant stages of Leishmania and Trypanosoma cruzi, which have been linked to therapeutic failure.Fil: Muraca, Giuliana Sabrina. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Ministerio de Salud. Administración Nacional de Medicamentos, Alimentos y Tecnología Médica; ArgentinaFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Sbaraglini, Maria Laura. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Fávaro, Wagner J.. Universidade Estadual Do Campinas. Instituto de Biologia. Departamento de Biologia Estructural y Funcional.; BrasilFil: Durán, Nelson. Universidade Estadual Do Campinas. Instituto de Biologia. Departamento de Biologia Estructural y Funcional.; Brasil. Universidad Federal do Abc; BrasilFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Talevi, Alan. Universidad Nacional de La Plata. Facultad de Ciencas Exactas. Laboratorio de Investigación y Desarrollo de Bioactivos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Bacterial cellulose-based materials as dressings for wound healing

Bacterial cellulose (BC) is produced by several microorganisms as extracellular structures and can be modified by various physicochemical and biological strategies to produce different cellulosic formats. The main advantages of BC for biomedical applications can be summarized thus: easy moldability, purification, and scalability; high biocompatibility; and straightforward tailoring. The presence of a high amount of free hydroxyl residues, linked with water and nanoporous morphology, makes BC polymer an ideal candidate for wound healing. In this frame, acute and chronic wounds, associated with prevalent pathologies, were addressed to find adequate therapeutic strategies. Hence, the main characteristics of different BC structures—such as membranes and films, fibrous and spheroidal, nanocrystals and nanofibers, and different BC blends, as well as recent advances in BC composites with alginate, collagen, chitosan, silk sericin, and some miscellaneous blends—are reported in detail. Moreover, the development of novel antimicrobial BC and drug delivery systems are discussed.Centro de Investigación y Desarrollo en Fermentaciones Industriale

Multi-target drug with potential applications: violacein in the spotlight

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein’s action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries.Fil: Durán, Nelson. Universidade Estadual de Campinas; BrasilFil: Nakazato, Gerson. Universidade Estadual de Londrina; BrasilFil: Durán, Marcela. Universidade Estadual de Campinas; BrasilFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Stanisic, Danijela. Universidade Estadual de Campinas; BrasilFil: Brocchi, Marcelo. Universidade Estadual de Campinas; BrasilFil: Fávaro, Wagner J.. Universidade Estadual de Campinas; BrasilFil: Ferreira Halder, Carmen V.. Universidade Estadual de Campinas; BrasilFil: Justo, Giselle Z.. Universidade Federal de Sao Paulo.; BrasilFil: Tasic, Ljubica. Universidade Estadual de Campinas; Brasi

Nanostructured Lipid Carriers Loaded with Dexamethasone Prevent Inflammatory Responses in Primary Non-Parenchymal Liver Cells

Liver inflammation represents a major clinical problem in a wide range of pathologies. Among the strategies to prevent liver failure, dexamethasone (DXM) has been widely used to suppress inflammatory responses. The use of nanocarriers for encapsulation and sustained release of glucocorticoids to liver cells could provide a solution to prevent severe side effects associated with systemic delivery as the conventional treatment regime. Here we describe a nanostructured lipid carrier developed to efficiently encapsulate and release DXM. This nano-formulation proved to be stable over time, did not interact in vitro with plasma opsonins, and was well tolerated by primary non-parenchymal liver cells (NPCs). Released DXM preserved its pharmacological activity, as evidenced by inducing robust anti-inflammatory responses in NPCs. Taken together, nanostructured lipid carriers may constitute a reliable platform for the delivery of DXM to treat pathologies associated with chronic liver inflammation.Fil: Medina Montano, Carolina. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Gambaro, Rocío Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Limeres, María José. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Svensson, Malin. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Padula, Gisel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Chain, Cecilia Yamil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Cisneros, José Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Castro, Guillermo Raul. Laboratorio Max Planck de Biologia Estructural, Quimica y Biofisica Molecular de Rosario ; Centro de Estudios Interdisciplinarios ; Universidad Nacional de Rosario; . Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Grabbe, Stephan. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Bros, Matthias. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Gehring, Stephan. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Cacicedo, Maximiliano Luis. Johannes Gutenberg Universitat Mainz; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentin

Enzymes and biopolymers: The opportunity for the smart design of molecular delivery systems

Enzymes exhibit a tremendous potential due to the catalytic activity in response to physiological conditions and specific microenvironments. Exploiting these properties in combination with the versatility of biopolymers, a fascinating field for the rational development of a new class of “smart” delivery systems for therapeutic molecules is proposed. Many strategies have been recently developed to produce matrices with the desirable properties of molecular release, and enzymes could be playing a relevant role in modify the chemical composition of the polymers, the porosity and surface area of the matrices and modulate the kinetic of controlled release. Enzyme based computational systems have appeared as a relevant complementary tool to design novel smart bioactive matrices for programmable drug delivery. The present review is reporting the recent advances and projections of smart biopolymeric matrices activated by enzymes for sustained release of therapeutic molecules, highlighting various applications in the area of advanced drug delivery.Fil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Islan, German Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina. Universidad Nacional de Rosario. Centro de Estudios Interdisciplinarios; Argentin

Microbial production and recovery of hybrid biopolymers from wastes for industrial applications- a review

Agro-industrial wastes to be a global concern since agriculture and industrial processes are growing exponentially with the fast increase of the world population. Biopolymers are complex molecules produced by living organisms, but also found in many wastes or derived from wastes. The main drawbacks for the use of polymers are the high costs of the polymer purification processes from waste and the scale-up in the case of biopolymer production by microorganisms. However, the use of biopolymers at industrial scale for the development of products with high added value, such as food or biomedical products, not only can compensate the primary costs of biopolymer production, but also improve local economies and environmental sustainability. The present review describes some of the most relevant aspects related to the synthesis of hybrid materials and nanocomposites based on biopolymers for the development of products with high-added value.Fil: Horue, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Cacicedo, Maximiliano Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentin

Development of biocarrier for violacein controlled release in the treatment of cancer

Violacein is a purple pigment member of the indocarbazole family synthesized by Gram(-) bacteria and displays many beneficial activities for human health. However, the medical use of violacein is very limited since the molecule is extremely hydrophobic. An emulsion of violacein and polyoxyethylene sorbitan monolaurate showed high stability in aqueous solutions at 37 degrees C for 6 days. Pectin-gelatin coating provides stability to the emulsion in simulated digestive fluids and modifies the violacein kinetic release. Biophysical analyses of hybrid pectin-gelatin microspheres by TEM, DLS, XRD, and DSC revealed a highly homogeneous surface of microspheres, amorphous content of violacein in the matrix, and increased structure stability. Kinetic studies of different pectin-gelatin microsphere formulations were performed under different environmental conditions simulating the digestive tract. Controlled release of Violacein from microspheres were examined using six semi-empirical and structured models. Violacein emulsions drastically decreased the HTC-116 colon cancer cell viability, but the effect was attenuated by the microsphere biopolymer coating136122130The present work was supported by Argentine grants from CONICET (National Council for Science and Technology, PIP 0498), The National Agency of Scientific and Technological Promotion (ANPCyT, PICT 2016-4597), UNLP (National University of La Plata, 11/X701) to GRC. We appreciate the kind gift of HCT116 cell line from Prof. Dr. M.R. Gonzalez Baró (INIBIOLP, University of La Plata

Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease, and leishmaniasis) are neglected tropical infectious diseases that mainly affect socioeconomically vulnerable populations. The available therapeutics display substantial limitations, among them limited efficacy, safety issues, drug resistance, and, in some cases, inconvenient routes of administration, which made the scenarios with insufficient health infrastructure settings inconvenient. Pharmaceutical nanocarriers may provide solutions to some of these obstacles, improving the efficacy-safety balance and tolerability to therapeutic interventions. Here, we overview the state of the art of therapeutics for trypanosomatid-caused diseases (including approved drugs and drugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriers encapsulating approved and non-approved drugs for these diseases. Numerous studies have focused on the obtention and preclinical assessment of lipid nanocarriers, particularly those addressing the two currently most challenging trypanosomatid-caused diseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studies suggest that delivering the drugs using such type of nanocarriers could improve the efficacy-safety balance, diminishing cytotoxicity and organ toxicity, especially in leishmaniasis. This constitutes a very relevant outcome, as it opens the possibility to extended treatment regimens and improved compliance. Despite these advances, last-generation nanosystems, such as targeted nanocarriers and hybrid systems, have still not been extensively explored in the field of trypanosomatid-caused conditions and represent promising opportunities for future developments. The potential use of nanotechnology in extended, well-tolerated drug regimens is particularly interesting in the light of recent descriptions of quiescent/dormant stages of Leishmania and Trypanosoma cruzi, which have been linked to therapeutic failure.Laboratorio de Investigación y Desarrollo de BioactivosCentro de Investigación y Desarrollo en Fermentaciones Industriale