Laboratorio de Investigación y Desarrollo de Métodos Analíticos (LIDMA)

Machine learning-assisted spectral optimization for improved PARAFAC modeling in fluorescence-based determination of carbamate pesticides

2026-06-29T20:25:02Z

Articulo Microchemical Journal; vol. 227 The extensive use of carbamate pesticides such as aminocarb and carbaryl has raised increasing concerns due to their persistence and potential impact on environmental and food safety. Their inconsistent regulation and occurrence at trace levels in complex matrices highlight the need for sensitive and reliable analytical method ologies for their determination. Here, a fluorescence-based chemometric strategy integrating PARAllel FACtor analysis (PARAFAC) analysis with a machine learning (ML)-assisted workflow is proposed, where ML is used to guide spectral variable selection, leading to improved PARAFAC performance and enhanced second-order cali bration in complex matrices. Excitation–emission matrices (EEMs) were decomposed using PARAFAC, while ML was employed to unfold the data, select optimal linear models, and identify informative spectral regions. This approach enabled selective resolution and accurate quantification of both analytes in tap water and orange juice, even in the presence of matrix interferences. The method showed excellent predictive performance, with co efficients of determination (R2) higher than 0.99 and 0.98 for tap water and orange juice, respectively, REP values below 10% and 15%, and recovery values ranged from 94 to 107%. ML-assisted spectral optimization significantly improved PARAFAC performance in complex matrices in reducing interferences. Limits of detection of 7 nM for carbaryl and 72 nM for aminocarb were achieved, comparable to conventional methods. Similar results were obtained against an HPLC–FLD reference method, while improved sustainability was demonstrated by a higher AGREE score (0.77 vs 0.64). The proposed ML-guided PARAFAC strategy provides a robust, accurate, and environmentally friendly alternative for carbamate simultaneous determination in complex matrices.

Síntesis y caracterización de polímeros de coordinación de lantánidos: potencial aplicación a la determinación de contaminantes ambientales mediante metodologías fotoluminiscentes

2023-11-21T20:07:13Z

Objeto de conferencia XII Congreso Argentino de Química Analítica (San Juan, 12 al 15 de septiembre de 2023) En el presente trabajo, se llevó a cabo la síntesis del polímero de coordinación TbBTC a partir de ácido bencen-1,3,5-tricarboxílico (H3BTC) y nitrato de terbio hexahidratado en medio agua/etanol. Se obtuvieron nanoestructuras alargadas (nanobelts) que exhiben una emisión fotoluminiscente característica del terbio, con tiempos de vida del orden de los mili-microsegundos. Por otra parte, se incluyó al TbBTC en matrices poliméricas sol-gel funcionalizadas con distintos grupos, utilizando tetraetoxisilano (TEOS) como entrecruzante y dos precursores funcionales (3-aminopropil trietoxisilano, APTES; 3-mercaptopropil trimetoxisilano, MPTS), obteniéndose un material híbrido fotoluminiscente. Los materiales desarrollados se caracterizaron morfológicamente por microscopía electrónica de barrido (SEM); se estudiaron sus propiedades ópticas, en suspensión y en estado sólido, y cómo éstas se ven afectadas por la presencia de ciertos analitos de interés a partir de ensayos de contacto en solución acuosa.

Exploring different high-capacity tools and extraction modes to characterize the aroma of brewed coffee

2023-11-17T20:06:53Z

Articulo Analytical and Bioanalytical Chemistry; vol. 415 In the present work, the potential beneft of using multi-cumulative trapping headspace extraction was explored by comparing the results using solid-phase microextraction (SPME) coated with divinylbenzene/carboxen/polydimethylsiloxane and a probe-like tool coated with polydimethylsiloxane. The efciency of a single 30-min extraction, already explored in previous work, was compared with that of multiple shorter extractions. We evaluated three diferent conditions, i.e., three repeated extractions for 10 min each from diferent sample vials (for both the probe-like tool and SPME) or from the same vial (for SPME) containing brewed cofee. The entire study was performed using comprehensive two-dimensional gas chromatography coupled with mass spectrometry. The two-dimensional plots were aligned and integrated using a tile-sum approach before any statistical analysis. A detailed comparison of all the tested conditions was performed on a set of 25 targeted compounds. Although a single 30-min extraction using the probe-like tool provided a signifcantly higher compound intensity than SPME single extraction, the use of multiple shorter extractions with SPME showed similar results. However, multiple extractions with the probe-like tool showed a greater increase in the number of extracted compounds. Furthermore, an untargeted crosssample comparison was performed to evaluate the ability of the two tested tools and the diferent extraction procedures in diferentiating between espresso-brewed cofee samples obtained from capsules made of diferent packaging materials (i.e., compostable capsules, aluminum capsules, aluminum multilayer pack). The highest explained variance was obtained using the probe-like tool and multiple extractions (91.6% compared to 83.9% of the single extraction); nevertheless, SPME multiple extractions showed similar results with 88.3% of variance explained.

Enantioseparation of α-amino acids by means of Cinchona alkaloids as selectors in chiral ligand-exchange chromatography

2023-04-13T20:40:26Z

Articulo Journal of Chromatography A; vol. 1298 A conventional nonchiral column was used for the enantioseparation of several racemic a-amino acids (native and derivatized) through the use of Cinchona alkaloids as chiral selectors along with Cu(II) ions in chiral ligand-exchange chromatography. The mobile phase composition (i.e., the organic modifier content and pH) was studied in order to modulate retention and enantioselectivity. Good enantioseparation of many amino acids was obtained using equimolar amounts of Cu(II) and either cinchonidine, quinine or quinidine as chiral selectors in the mobile phase. The molecular geometry of the diastereomeric complexes formed was modeled and energetic differences between both compounds were calculated by methods based on semi-empirical force-field. Good correlations were obtained between experimental enantioselectivity factors and calculated energetic differences.

Development of a background electrolyte for the determination of inorganic cations in high ionic strength samples by capillary electrophoresis with indirect UV-absorption detection

2022-09-15T20:04:43Z

Preprint Journal of chromatography; vol. 1645 In this study, a background electrolyte capable to separate and quantify inorganic cations in high ionic strength samples by UV-absorption indirect detection was designed. In this regard, the four most abundant monovalent and divalent cations in earth crust (K+, Na+, Ca+2, Mg+2) were selected as model compounds. A group of small carboxylic acids and, several toluidines and pyridines were evaluated as mild strength complexing agents and chromophoric probes, respectively. The optimized background electrolyte was composed of 200 mM 2,4,6-trimethylpyridine as the chromophoric probe, 250 mM lactic acid as the weak complexing agent and pH buffering reagent (adjusted to pH 4.5), and 5% v/v methanol as organic solvent modifier. Based on a minimum number of components, it provided outstanding separation performance in less than 4 min in a wide linear dynamic range (10 - 2500 µg·mL−1). Performances were contrasted against a reference method based on conductometric detection. Furthermore, studies of separation efficiency and peak shape were carried out at different analyte concentrations in high electric conductivity solutions. The herein developed method demonstrated exceptional features in terms of limits of detection (~10 µg·mL−1), resolution, speed of analysis, sensitivity and peak capacity in high electric conductivity samples. Moreover, the method was successfully applied to high ionic strength samples such as rock digest, sea water, soy sauce and isotonic drinks.

Antioxidant Profiling of Ginger via Reaction Flow Chromatography

2022-07-08T20:04:12Z

Articulo Natural Product Communications; vol. 16, no. 9 Reaction flow (RF) chromatography is a powerful and efficient approach that utilizes conventional high-performance liquid chromatography (HPLC)–ultraviolet (UV)–visible detection. This technique exploits a novel column end-fitting and an extra HPLC pump that delivers a reagent specific for selective detection, in particular the antioxidant profiling of natural products. This study employed RF for the first time to identify antioxidants in a commercial ginger sample. This demonstrated the previously validated assay’s ease and power to extract information about the natural product’s antioxidant properties. Due to the simplicity involved with data analysis and peak matching process, the following information was revealed between the chemical and antioxidant profiles: three of the strongest antioxidant activity peaks in the ginger sample (593 nm) did not correlate with the three most abundant chemical profile peaks (UV absorbance at 254 and 280 nm); the ratio of seven antioxidant peaks may be potentially used for food authenticity purposes, and future research should target these peaks for the early discovery of novel antioxidants sourced in ginger. Utilization of this previously validated assay provided the resolution of numerous peaks in the ginger extract and information associated with their antioxidant attributes and chemical abundance. This approach is more informative than total antioxidant assays that lack compound specificity information. Furthermore, it is superior to mass spectrometric (MS) assays that cannot evaluate each compound’s antioxidant strength, and does not involve the expense involved in the acquisition and maintenance of the MS detection hardware, and does not require the high level of expertise needed to conduct the MS data analysis.

Application of Machine Learning Approaches to Identify New Anticonvulsant Compounds Active in the 6 Hz Seizure Model

2022-07-07T04:05:02Z

Objeto de conferencia II Latin American Workshop, LAWCN 2019 (Brasil, 18 al 20 de septiembre de 2019); Computational Neuroscience. LAWCN 2019. Communications in Computer and Information Science Epilepsy is the second most common chronic brain disorder, affecting 65 million people worldwide. According to the NIH’s Epilepsy Therapy Screening Program, evaluation of potential new antiepileptic drug candidates begins with assessment of their protective effects in two acute seizure models in mice, the Maximal Electroshock Seizure test and the 6 Hz test. The latter elicits partial seizures through an electrical stimulus of 44 mA, at which many clinically established anti-seizure drugs do not suppress seizures. The inclusion of this “high-hurdle” acute seizure assay at the initial stage of the drug identification phase is intended to increase the probability that agents with improved efficacy will be detected. In this work, we have used machine learning approximations to develop in silico models capable of identifying novel anticonvulsant drugs with protective effects in the 6 Hz seizure model. Linear classifiers based on Dragon conformation-independent descriptors were generated through an in-house routine in R environment and validated through standard validation procedures. They were later combined through different ensemble learning schemes. The best ensemble comprised the 29 best-performing models combined using the MIN operator. With the objective of finding new drug repurposing opportunities (i.e. identifying second or further therapeutic indications, in our case anticonvulsant activity, in existing drugs), such model ensemble was applied in a virtual screening campaign of DrugBank and Sweetlead databases. 28 approved drugs were identified as potential protective agents in the 6 Hz model. The present study constitutes an example of the use of machine learning approximations to systematically guide drug repurposing projects.

Total Antioxidant Capacity with Peak Specificity via Reaction Flow Chromatography and the Ferric Reducing Antioxidant Power Assay

2022-06-09T04:04:10Z

Articulo Food Analytical Methods; vol. 13, no. 3 An established ferric reducing antioxidant power (FRAP) assay was optimised by preparation of the derivatisation reagent in 300 mM formate instead of 300 mM acetate conditions, resulting in increased sensitivity signal to noise responses by up to five to ten times. The quantitative protocol for selective detection of antioxidants via a HPLC post column derivatisation (PCD) technique using the 300 mM formate FRAP reagent conditions was then transformed into a high-speed qualitative screening protocol by utilizing an emerging technology ‘reaction flow (RF) chromatography’. Reaction flow chromatography’s ability to screen for total antioxidant capacity with additional peak specificity/profile information of active peaks could be achieved in under 2 min.

Ensemble learning application to discover new trypanothione synthetase inhibitors

2022-04-02T04:04:31Z

Articulo Molecular Diversity; vol. 25, no. 3 Trypanosomatid-caused diseases are among the neglected infectious diseases with the highest disease burden, affecting about 27 million people worldwide and, in particular, socio-economically vulnerable populations. Trypanothione synthetase (TryS) is considered one of the most attractive drug targets within the thiol-polyamine metabolism of typanosomatids, being unique, essential and druggable. Here, we have compiled a dataset of 401 T. brucei TryS inhibitors that includes compounds with inhibitory data reported in the literature, but also in-house acquired data. QSAR classifiers were derived and validated from such dataset, using publicly available and open-source software, thus assuring the portability of the obtained models. The performance and robustness of the resulting models were substantially improved through ensemble learning. The performance of the individual models and the model ensembles was further assessed through retrospective virtual screening campaigns. At last, as an application example, the chosen model-ensemble has been applied in a prospective virtual screening campaign on DrugBank 5.1.6 compound library. All the in-house scripts used in this study are available on request, whereas the dataset has been included as supplementary material.

8º Congreso Argentino de Química Analítica: Libro de resúmenes

2022-03-30T04:05:43Z

Libro Publicación que recopila los resúmenes de los trabajos presentados en el 8º Congreso Argentino de Química Analítica, celebrado en la ciudad de La Plata, del 3 al 6 de noviembre de 2015. Los trabajos se hallan distribuidos en Conferencias plenarias, Conferencias semiplenarias, Comunicaciones Orales y Pósters. Asociación Argentina de Químicos Analíticos (AAQA)

Fast determination of harmala alkaloids in edible algae by capillary electrophoresis mass spectrometry

2022-03-22T04:05:05Z

Articulo Analytical and Bioanalytical Chemistry; vol. 407, no. 13 The use of algae as a foodstuff is rapidly expanding worldwide from the East Asian countries, where they are also used for medical care. Harmala alkaloids (HAlk) are a family of bioactive compounds found in the extracts of some plants, including wakame (Undaria pinnatifida), an edible marine invasive algae. HAlks are based on a characteristic βcarboline structure with at least one amino ionizable group. In this work, we report the successful separation of a mixture of six HAlks (harmine, harmaline, harmol, harmalol, harmane, and norharmane) by capillary electrophoresis ion-trap mass spectrometry (CE-IT-MS) in less than 8 min. Optimum separation in fused-silica capillaries and detection sensitivity in positive-ion mode were achieved using a background electrolyte (BGE) with 25 mmol L⁻¹ ammonium acetate (pH 7.8) and 10 % (v/v) methanol, and a sheath liquid with 60:40 (v/v) isopropanol–water and 0.05 % (v/v) formic acid. The separation method was validated in terms of linearity, limits of detection and quantification, repeatability, and reproducibility. Later, a sample pretreatment was carefully optimized to determine HAlks in commercial wakame samples with excellent recovery and repeatability. For the complex wakame extracts, the MS–MS fragmentation patterns of the different HAlks were useful to ensure a reliable identification. The complete procedure was validated using the standardaddition calibration method, determining matrix effects on the studied compounds. Harmalol, harmine, and harmaline were naturally present in the samples and were quantified at very low concentrations, ranging from 7 to 24 μg kg⁻¹ dry algae.

Development of a green and efficient methodology for the heterocyclic aromatic amine determination in biomass samples generated from cigarette combustion and tobacco

2022-03-18T04:30:38Z

Articulo Environmental science and pollution research international; vol. 28, no. 5 A green methodology was developed for the analysis of ten heterocyclic aromatic amines (HAAs) in biomass samples from cigarette combustion such as mainstream smoke, paper ashes, as well as tobacco and paper wraps. The cellulose filter used for sample collection was also evaluated. This strategy was based on ultrasound-assisted extraction (UAE) associated with a solid-phase extraction procedure employing multi-walled carbon nanotubes (MWCNTs-SPE) as a cleanup step followed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Under optimal experimental conditions, the linearity of the method was in the range from 0.08 to 160 ng cig-1, with correlation coefficients (R2) higher than 0.991. The limits of detection resulted to be between 0.03 and 0.63 ng cig-1. Concentrations of the HAAs in the mainstream smoke were from 5.7 to 145.2 ng cig-1 and in paper ashes from 0.1 to 0.6 ng cig -1, while in tobacco were between 1.0 and 38.5 ng cig-1. Meanwhile, no HAA contribution was observed in the case of paper wraps and the filter used for sample collection. The knowledge of the presence and the concentration levels of the selected HAAs in each cigarette’s physical component after its combustion is essential to understand the formation processes and contribution during cigarette burning. Besides, this is the first report about the presence of some HAAs in the proposed samples. Finally, a comparative study was employed to classify the sustainability of several recent approaches for HAA extraction from cigarette combustion samples using Green Certificate as a metric tool.

Better than bench top: High speed antioxidant screening via the cupric reducing antioxidant capacity reagent and reaction flow chromatography

2021-11-29T20:05:44Z

Preprint Microchemical Journal; vol. 152 This study is based upon a recently established method for quantification of the antioxidant capacity of natural samples via a HPLC separation and a hyphenated selective detection (post-column derivatization with cupric reducing antioxidant capacity reagent) technique. This protocol demonstrated the main improvements to transform the quantitative protocol into a high-speed qualitative automated assay to screen samples for their potential total antioxidant capacity, typically performed via manual mixing of the sample and derivatisation and measured on a 96 well plate reader/bench top UV–Vis spectrophotometer. This approach with automated mixing is a more informative alternative for total antioxidant capacity as the antioxidant peaks are profiled for each sample within four minutes. This antioxidant profile may be used for routine analysis of raw materials and/or a guide for targeted approaches for structure elucidation for laboratories interested in early drug discovery, natural product research and the search of alternative antioxidant additives in consumer goods/therapeutics. This technique could also be used to monitor the stability, alteration or adulteration of manufactured goods containing antioxidants.

Determination of thermodynamic binding constants by affinity capillary electrophoresis

2021-11-26T20:04:47Z

Preprint Talanta; vol. 192 A strategy to study thermodynamic binding constants by affinity capillary electrophoresis (ACE) is presented. In order to simplify mathematical treatment, analogy with acid-base dissociation equilibrium is proposed: instead of ligand concentration [X], negative logarithm of ligand concentration (or activity), pX = -log[X], is used. On this base, and taking into account ionic activities, a general procedure for obtaining thermodynamic binding constants is proposed. In addition, the method provides electrophoretic mobilities of the free analyte and analyte-ligand complex, even when binding constants are low and thus, the complexed analyte fraction is also low. This is useful as a base to rationally analyze a diversity of situations, i.e., different mathematical dependencies are obtained when analytes and ligands with different charges are combined. Practical considerations are given for carrying out a full experimental design. Enantiomeric ACE separation based on the use of chiral selectors is addressed. 2-hydroxypropyl-β-cyclodextrin was chosen as a model ligand, and both enantiomeric forms of four pharmaceutical drugs (propranolol, pindolol, oxprenolol and homatropine methylbromide) were considered as model analytes. Practical aspects are detailed and thermodynamic binding constants as well as free and complexed analytes mobilities are determined.

Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils

2022-08-16T15:12:07Z

Preprint Journal of Molecular Liquids; vol. 314 We investigated the effect of the point substitutions in the N-terminal domain of the yeast prion protein Sup35 (Sup35NMp) on the structure of its amyloid fibrils. As the objects of the study, proteins with mutations that have different influence on the [PSI+] prion propagation, but do not prevent the aggregation of Sup35NMp in vitro were chosen. The use of the wide range of physico-chemical methods allowed us to show significant differences in the structure of these aggregates, their physical size, clumping tendency. Also we demonstrated that the fluorescent probe thioflavin T (ThT) can be successfully used for investigation of subtle changes in the structural organization of fibrils formed from various Sup35NMp. The obtained results and our theoretical predictions allowed us to conclude that some of selected amino acid substitutions delimit the region of the protein that forms the core of amyloid fibrils, and change the fibrils structure. The relationship of structural features of in vitro Sup35NMp amyloid aggregates with the stability of the [PSI+] prion in vivo allowed us to suggest that oligopeptide repeats (R) of the amyloidogenic N-terminal domain of Sup35NMp from R0 to R2 play a key role in protein aggregation. Their arrangement rather than just presence is critical for propagation of the strong [PSI+] prion variants. The results confirm the suitability of the proposed combination of theoretical and empirical approaches for identifying changes in the amyloid fibrils structure, which, in turn, can significantly affect both the functional stability of amyloid fibrils and their pathogenicity.

Multi-response optimization of a green solid-phase extraction for the analysis of heterocyclic aromatic amines in environmental samples

2021-10-22T20:06:38Z

Preprint Analytical Methods; vol. 12, no. 11 Herein, a method for the multi-response optimization of a green and efficient solid phase extraction (SPE) sample treatment using non-modified multi-walled carbon nanotubes combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the quantification of ten heterocyclic aromatic amines (HAAs) in river and reservoir surface water samples. The proposed methodology was evaluated by employing experimental designs, which made the approach green. Ultra-trace amounts of HAAs were retained in the SPE cartridge. Then, the analytes were removed from the carbon nanotubes with 0.8 mL of a mixture of acetonitrile/water with 0.1% of formic acid. Under the optimal conditions, linearity was achieved for concentration levels ranging from 0.20 μg L−1 to 500 μg L−1, with regression coefficients (R2) in the range of 0.990 to 0.998. Limits of detection varying from 0.06 μg L−1 and 0.23 μg L−1 were attained, the relative standard deviations (n = 3) varied from 1.7 to 6.4, and the extraction recoveries ranged from 90.6% to 106.0% for all the analytes. The results of the presence of HAAs found in the river samples demonstrated levels ranging from 0.16 μg L−1 to 0.53 μg L−1; meanwhile, in the reservoir samples, the levels were higher, ranging from 0.37 μg L−1 to 0.93 μg L−1. Finally, a comparative discussion was applied to assess the greenness of approaches for the determination of heterocyclic aromatic amines in surface water using the available metrics.

Enantiomeric separations by capillary electrophoresis: Theoretical method to determine optimum chiral selector concentration

2021-09-18T04:06:38Z

Preprint Journal of Chromatography. A; vol. 1539 A method to optimize the ligand concentration [S] in the background electrolyte of capillary electrophoresis separations is presented. It is based on the use of a model which predicts apparent electrophoretic mobilities as a function of ligand concentration (expressed as p[S] = −log[S]). This model is employed to compose the expression of a recently proposed criterion to qualify separations in electrophoresis. Two strategies to find the optimum p[S], leading to the best separation of all compounds, are explained: 1.- a graphical method using a windows map depicting the single separation criteria between all possible combination of compounds by pairs, and 2.- an analytical method where an extended multicriterion optimization function is composed and optimum p[S] is found by mathematical maximization. The procedure is applied to a hard-to-separate model system: enantiomeric separations of racemic mixtures. 2-Hydroxypropyl-β-cyclodextrin was chosen as a model ligand, and four pharmaceutical drugs as model analytes. In order to demonstrate the performance of the procedure, results of electrophoretic separations obtained at p[S] found as optimum are compared with separations obtained at p[S] values slightly higher and lower than the optimum.

Photografted methacrylate-based monolithic columns coated with cellulose tris(3,5-dimethylphenylcarbamate) for chiral separation in CEC

2021-09-18T04:06:46Z

Preprint Journal of Separation Science; vol. 41, no. 6 A chiral capillary monolithic column for enantiomer separation in capillary electrochromatography was prepared by coating cellulose tris(3,5-dimethylphenylcarbamate) on porous glycidyl methacrylate-co-ethylene dimethacrylate monolith in capillary format grafted with chains of [2(methacryloyloxy)ethyl] trimethylammonium chloride. The surface modification of the monolith by the photografting of [2(methacryloyloxy)ethyl] trimethylammonium chloride monomer as well as the coating conditions of cellulose tris(3,5-dimethylphenylcarbamate) onto the grafted monolithic scaffold were optimized to obtain a stable and reproducible chiral stationary phase for capillary electrochromatography. The effect of organic modifier (acetonitrile) in aqueous mobile phase for the enantiomer separation by capillary electrochromatography was also investigated. Several pairs of enantiomers including acidic, neutral, and basic analytes were tested and most of them were partially or completely resolved under aqueous mobile phases. The prepared monolithic chiral stationary phases exhibited a good stability, repeatability, and column-to-column reproducibility, with relative standard deviations below 11% in the studied electrochromatographic parameters.

Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects

2021-09-10T20:08:37Z

Revision Frontiers in Molecular Biosciences; vol. 7 In the golden age of pharmaceutical nanocarriers, we are witnessing a maturation stage of the original concepts and ideas. There is no doubt that nanoformulations are extremely valuable tools for drug delivery applications; the current challenge is how to optimize them to ensure that they are safe, effective and scalable, so that they can be manufactured at an industrial level and advance to clinical use. In this context, lipid nanoparticles have gained ground, since they are generally regarded as non-toxic, biocompatible and easy-to-produce formulations. Pharmaceutical applications of lipid nanocarriers are a burgeoning field for the transport and delivery of a diversity of therapeutic agents, from biotechnological products to small drug molecules. This review starts with a brief overview of the characteristics of solid lipid nanoparticles and discusses the relevancy of performing systematic preformulation studies. The main applications, as well as the advantages that this type of nanovehicles offers in certain therapeutic scenarios are discussed. Next, pharmacokinetic aspects are described, such as routes of administration, absorption after oral administration, distribution in the organism (including brain penetration) and elimination processes. Safety and toxicity issues are also addressed. Our work presents an original point of view, addressing the biopharmaceutical aspects of these nanovehicles by means of descriptive statistics of the state-of-the-art of solid lipid nanoparticles research. All the presented results, trends, graphs and discussions are based in a systematic (and reproducible) bibliographic search that considered only original papers in the subject, covering a 7 years range (2013-today), a period that accounts for more than 60% of the total number of publications in the topic in the main bibliographic databases and search engines. Focus was placed on the therapeutic fields of application, absorption and distribution processes and current efforts for the translation into the clinical practice of lipid-based nanoparticles. For this, the currently active clinical trials on lipid nanoparticles were reviewed, with a brief discussion on what achievements or milestones are still to be reached, as a way of understanding the reasons for the scarce number of solid lipid nanoparticles undergoing clinical trials.

Peptidasas y lipasas vegetales como biocatalizadores en la obtención de tensioactivos derivados de aminoácidos

2023-02-03T14:35:53Z

Objeto de conferencia XIX Congreso Argentino de Catálisis y VIII Congreso de Catálisis del Mercosur (Bahía Blanca, 21 al 23 de septiembre de 2015) Se sintetizaron compuestos derivados de aminoácidos con potencial actividad superficial mediante reacciones de condensación de Arg, Gly, Ala y Leu con alquilaminas y alcoholes alifáticos (decil y dodecilamina; decanol y dodecanol). Dichas reacciones fueron catalizadas por peptidasas vegetales cisteínicas, una de origen comercial (papaína) y otra extraída del látex de la enredadera nativa Araujia sericifera. Asimismo, se probó la capacidad de la lipasa obtenida de dicho látex para catalizar estas reacciones. Las estrategias ensayadas fueron control termodinámico y control cinético. Las alquilamidas derivadas de Ala y Gly pudieron ser sintetizadas mediante el enfoque termodinámico con muy buenos rendimientos para Ala pero más bajos para Gly. Dado que los derivados de Leu no pudieron ser sintetizados mediante esta estrategia, y para aumentar el rendimiento de los derivados de Gly, se ensayó la síntesis por control cinético previa esterificación de los dadores de acilo. Mediante esta metodología, se obtuvieron rendimientos cercanos al 90% para ambos dadores de acilos empleando papaína. Se utilizó este enfoque para sintetizar los derivados de Arg utilizando los tres biocatalizadores y los cuatro nucleófilos, resultando papaína la enzima más eficiente. Se escalaron las síntesis de las alquilamidas utilizando papaína como biocatalizador, a fin de caracterizar los productos obtenidos.; Amino acid-based compounds with potential surface activity were synthezised by condensation reactions between Arg, Gly, Ala and Leu with alkyl amines and aliphatic alcohols (decyl and dodecyl amines; decanol and dodecanol).Reactions were catalyzed by plant cysteine peptidases, one form commercial origin (papain) and another obtained from the native vine Araujia sericifera latex. A lipase obtained from the same plant latex (ASL) was also proved as biocatalyst. Both approaches, thermodynamic and kinetic controlled synthesis were tested. Ala derivatives were successfully synthezised under the thermodynamic approach, but the syntheses of Gly derivatives showed lower yields and Leu derivatives could not be synthezised. Kinetic controlled syntheses were tested after esterification of acyl donors. Higher yields of the Gly derivatives, as well as high yields of Leu derivatives could be reached using papain under this approach. Kinetic controlled synthesis was applied to produce the Arg derivatives using the three biocatalysts and the four nucleophiles, being papain the most efficient enzyme. Syntheses of alkylamides were scaled up using papain as biocatalyst in order to have enough product mass for characterization.