Abstract:

Author affiliation: Busatto, Carlos Alberto. Universidad Nacional del Litoral. Facultad de Ingeniería Química; Argentina.

En el presente trabajo de tesis se han desarrollado diferentes plataformas biodegradables para la liberación controlada de progesterona con el objetivo de sincronizar el celo en el ganado bovino. Los sistemas de liberación controlada basados en micropartículas y microgeles poliméricos presentan un especial interés debido a que poseen diversas ventajas, tales como fácil preparación y administración, no requieren intervención quirúrgica para remover el material al término de la liberación, y es posible controlar los tiempos de liberación/degradación en base a las propiedades fisicoquímicas del polímero. Se estudiaron tres matrices poliméricas biodegradables para la preparación de micropartículas: PLGA, quitosano y ácido hialurónico. Las micropartículas se obtuvieron empleando diferentes técnicas de preparación y fueron caracterizadas en cuanto a propiedades fisicoquímicas, degradabilidad y perfiles de liberación. Además, se desarrollaron modelos matemáticos de degradación de la matriz polimérica y de liberación controlada de progesterona.

In this thesis, different biodegradable platforms have been developed for the controlled release of progesterone intended for estrus synchronization in cattle. Polymeric microparticles and microgels are of special interest because they have several advantages, such as easy preparation and administration, do not require surgical intervention to remove the material at the end of the release period, and it is possible to control the release/degradation rates based on the physicochemical properties of the polymer. Three biodegradable polymeric matrices were studied for the preparation of microparticles: PLGA, chitosan and hyaluronic acid. The microparticles were obtained using different preparation techniques and were characterized in terms of physicochemical properties, degradability and release profiles. In addition, mathematical models of polymer degradation and controlled release of progesterone were developed.

Consejo Nacional de Investigaciones Científicas y Técnicas

Universidad Nacional del Litoral

Abstract:

Poly(lactic-co-glycolic acid) (PLGA) microparticles containing progesterone were prepared by the solvent extraction/evaporation and microfluidic techniques. Microparticles were characterized by their size distribution, encapsulation efficiency, morphology and thermal properties. The effect of particle size, polydispersity and polymer degradation on the in vitro release of the hormone was studied. A triphasic release profile was observed for larger microparticles, while smaller microspheres showed a biphasic release profile. This behavior is related to the fact that complete drug release was achieved in a few days for smaller microparticles, during which polymer degradation effects are still negligible. A mathematical model was developed that predicts the progesterone release profiles from different-sized PLGA microspheres. The model takes into account both the dissolution and diffusion of the drug in the polymeric matrix as well as the autocatalytic effect of polymer degradation. The model was adjusted and validated with novel experimental data. Simulation results are in very good agreement with experimental results.

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Pesoa, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Helbling, Ignacio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Abstract:

Poly(lactic-co-glycolic acid) (PLGA) microparticles containing progesterone were prepared by the solvent extraction/evaporation and microfluidic techniques. Microparticles were characterized by their size distribution, encapsulation efficiency, morphology and thermal properties. The effect of particle size, polydispersity and polymer degradation on the in vitro release of the hormone was studied. A triphasic release profile was observed for larger microparticles, while smaller microspheres showed a biphasic release profile. This behavior is related to the fact that complete drug release was achieved in a few days for smaller microparticles, during which polymer degradation effects are still negligible. A mathematical model was developed that predicts the progesterone release profiles from different-sized PLGA microspheres. The model takes into account both the dissolution and diffusion of the drug in the polymeric matrix as well as the autocatalytic effect of polymer degradation. The model was adjusted and validated with novel experimental data. Simulation results are in very good agreement with experimental results.

Author affiliation: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Helbling, Ignacio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Pesoa, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Abstract:

A new mathematical model for the prediction of the heterogeneous hydrolytic degradation of poly(D,L-lactide-co-glycolide) (PLGA)-based microspheres was developed. The model takes into account the autocatalytic effect of carboxylic groups and polymer composition on the degradation rate. It is based on mass balances for the different species, considering the kinetic and masstransport phenomena involved. The model estimates the evolution of average molecular weight, mass loss, and morphological change of the particles during degradation, and it was validated with novel experimental data. Theoretical predictions are in agreement with the hydrolysis data of PLGA microspheres (error values less than 5%). The model is able to predict the effect of particle size and molecular weight on the degradation of PLGA-based microspheres and estimates the morphological changes of the particles due to the autocatalytic effect.

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Pesoa, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Helbling, Ignacio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Abstract:

The homogeneous hydrolytic degradation of poly(lactic-co-glycolic acid) (PLGA) microspheres was investigated. A mathematical model was developed that estimates the evolutions of ester bonds concentrations and average molecular weights along the degradation process. The model is based on a detailed kinetic mechanism that includes the hydrolysis of the different types of ester bonds by random chain scission and considers the effect of polymer chemical composition and molecular structure. Novel and published experimental data were used to adjust and validate the model. The experimental work consisted of homogeneous hydrolytic degradation of PLGA microspheres. The predictions are in very good agreement with the experimental results.

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Berkenwald, Emilio. Instituto Tecnológico de Buenos Aires; Argentina

Author affiliation: Mariano, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Casis, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Abstract:

Lignins are natural polymers of the lignocellulosic biomass. Nowadays, there is a growing interest in developing value-added products based on lignins due to their renewability, low cost and abundance. In this work, lignin microspheres from organosolv and ionic isolation processes were prepared for the controlled release of atrazine. Microspheres were prepared by the solvent extraction/evaporation technique. The controlled release of atrazine from organosolv and ionic lignins microparticles was studied in water. Mobility experiments were performed in an agricultural soil from Argentina. The results showed that microparticles prepared using dichloromethane as the dispersed phase were spherical, while lignins dispersed in ethyl acetate produce irregular microparticles. Organosolv lignin microparticles presented higher encapsulation efficiency for all herbicide loads. About 98% and 95% of atrazine was released in 24 and 48 h approximately from organosolv and ionic lignin microparticles, respectively. The release profiles of atrazine from both lignin microparticles were not affected by the herbicide load. Atrazine mobility experiments in soil showed that about 80% of free atrazine was leached in 37 days, while 65.0% and 59.7% of the herbicide was leached from ionic and organosolv lignin microparticles, respectively. Thus, atrazine-loaded microparticles could reduce leaching compared to a commercial formulation of free atrazine.

Author affiliation: Taverna, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Lescano, Maia Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Nicolau, Veronica Viviana. Universidad Tecnológica Nacional. Facultad Regional San Francisco; Argentina

Author affiliation: Zalazar, Cristina Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Meira, Gregorio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Abstract:

The synthesis of new nanoporous materials based on molecularly imprinted polymers (MIPs) is investigated. The novel procedure combines the non-covalent imprinting method with the colloidal crystal template technique to produce membranes with pre-specified morphology capable of selectively recognizing progesterone. The colloidal crystals made of silica particles were obtained by Langmuir − Blodgett and self-assembly techniques, and exhibited a considerable control of the film thickness. Hydrogel films were prepared by copolymerization of acrylic acid and ethylene glycol dimethacrylate in the presence of 2,2′-azobisisobutyronitrile as initiator. The polymerization took place in the interspaces of the colloidal crystal and after the reaction was finished the silica particles were etched with hydrofluoric acid to produce a 3D ordered structure. The nanocavities derived from progesterone were distributed within the walls of the internal structure of the films. The equilibrium swelling properties of the MIPs were studied as a function of crosslinking degree and pH. The pore morphology of the film was analyzed by SEM. The MIP characterizations were accomplished by several techniques, e.g. Fourier transform infrared spectroscopy, DSC and evaluation of their sensing and selective properties.

Author affiliation: Casis, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina

Author affiliation: Fidalgo, María Marta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University Of Missouri; Estados Unidos

Author affiliation: Ravaine, Serge. Centre National de la Recherche Scientifique; Francia

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química (i); Argentina

Abstract:

Polymer microgels have received considerable attention due to their great potential in the biomedical field as drug delivery systems. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan composed of N-acetyl-D-glucosamine and D-glucuronic acid. This polymer is biodegradable, nontoxic, and can be chemically modified. In this work, a co-flow microfluidic strategy for the preparation of biodegradable HA microgels encapsulating hydrophobic drugs is presented. The approach relies on: (i) generation of a primary oil-in-water (O/W) nanoemulsion by the ultrasonication method, (ii) formation of a double oil-in-water-in-oil emulsion (O/W/O) using microfluidics, and (iii) cross-linking of microgels by photopolymerization of HA precursors modified with methacrylate groups (HA-MA) present in the aqueous phase of the droplets. The procedure is used for the encapsulation and controlled release of progesterone. Degradability and encapsulation/release studies in PBS buffer at 37 ºC in presence of different concentrations of hyaluronidase are performed. It is demonstrated that enzymatic degradation can be used to trigger the release of progesterone from microgels. This method provides precise control of the release system and can be applied for the encapsulation and controlled release of different types of hydrophobic drugs.

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Labie, H.. Universite de Bordeaux; Francia

Author affiliation: Lapeyre, V.. Universite de Bordeaux; Francia

Author affiliation: Auzely Velty, R.. Universite Joseph Fourier; Francia

Author affiliation: Perro, A.. Universite de Bordeaux; Francia

Author affiliation: Casis, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico Para la Industria Química; Argentina

Author affiliation: Ravaine, V.. Universite de Bordeaux; Francia

Abstract:

In this study, PLGA particle systems were studied for the controlled release of florfenicol, a broad spectrum antibiotic used in veterinary treatments. The emulsion-solvent evaporation technique was used for particle preparation. To evaluate the particle size, entrapment efficiency, and drug release behavior, factors such as solvent type, emulsification time and methods, and drug to polymer ratio were investigated. The results showed that the use of ethyl acetate and 2.5 min of ultrasonication or 30 min of homogenization can lead to sub-micron and micron-sized particles, respectively. Sizes between 200–300 nm and 2–3 μm were obtained for ultrasonication and homogenization procedures, respectively. Entrapment efficiencies were around 20% for all systems and release profiles were size dependent. In addition, a mathematical model was implemented to simulate the florfenicol transport. The model predicts the florfenicol release and takes into account the particle size, polymer molecular weight, and autocatalytic polymer degradation. Simulation results are in good agreement with experimental results.

Author affiliation: Karp, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Turino, Ludmila Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Abstract:

Purpose: Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5–8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. Methods: Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. Results: Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69–75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. Conclusion: The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

Author affiliation: Helbling, Ignacio Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Busatto, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Fioramonti, Silvana Alejandra. Universidad Nacional del Litoral; Argentina

Author affiliation: Pesoa, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Santiago, Liliana Gabriela. Universidad Nacional del Litoral; Argentina

Author affiliation: Estenoz, Diana Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina

Author affiliation: Luna, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; Argentina