Publications by authors named "Pasquale Gaudio"

58 Publications

Infectious Diseases Seeker (IDS): An Innovative Tool for Prompt Identification of Infectious Diseases during Outbreaks.

Int J Environ Res Public Health 2021 03 20;18(6). Epub 2021 Mar 20.

Department of Industrial Engineering, University of Rome "Tor Vergata", 00133 Rome, Italy.

Background: Several technologies for rapid molecular identification of pathogens are currently available; jointly with monitoring tools (i.e., web-based surveillance tools, infectious diseases modelers, and epidemic intelligence methods), they represent important components for timely outbreak detection and identification of the involved pathogen. The application of these approaches is usually feasible and effective when performed by healthcare professionals with specific expertise and skills and when data and resources are easily accessible. Contrariwise, in the field situation where healthcare workers or first responders from heterogeneous competences can be asked to investigate an outbreak of unknown origin, a simple and suitable tool for rapid agent identification and appropriate outbreak management is highly needed. Most especially when time is limited, available data are incomplete, and accessible infrastructure and resources are inadequate. The use of a prompt, user-friendly, and accessible tool able to rapidly recognize an infectious disease outbreak and with high sensitivity and precision may be a game-changer to support emergency response and public health investigations.

Methods: This paper presents the work performed to implement and test an innovative tool for prompt identification of infectious diseases during outbreaks, called Infectious Diseases Seeker (IDS). IDS is a standalone software that runs on the most common operative systems. It has been built by integrating a database containing an interim set of 60 different disease causative agents and COVID-19 data and is able to work in an off-line mode without requiring a network connection.

Results: IDS has been applied in a real and complex scenario in terms of concomitant infectious diseases (yellow fever, COVID-19, and Lassa fever), as can be in the second part of 2020 in Nigeria. The outcomes have allowed inferring that yellow fever (YF), and not Lassa fever, was affecting the area under investigation.

Conclusions: Our result suggests that a tool like IDS could be valuable for the quick and easy identification and discrimination of infectious disease outbreaks even when concurrent outbreaks occur, like for the case study of YF and COVID-19 pandemic in Nigeria.
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http://dx.doi.org/10.3390/ijerph18063216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003641PMC
March 2021

Coaxial semi-solid extrusion and ionotropic alginate gelation: A successful duo for personalized floating formulations via 3D printing.

Carbohydr Polym 2021 May 14;260:117791. Epub 2021 Feb 14.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano SA, Italy. Electronic address:

With the aim to fulfill the patient-centered approach of precision medicine, in this research, innovative floating drug delivery systems have been developed through the use of alginate matrix and fully characterized. Particularly, to exploit the ionotropic gelation of alginate, a customized coaxial extruder for Semi-solid Extrusion 3D printing, has been used for the simultaneous dispensing of ink gel (sodium alginate 6% w/v) and crosslinking gel (hydroxyethyl cellulose 3 %w/v, calcium chloride 0.1M and Tween 85 0.1% v/v). The latter also loaded with Propranolol Hydrochloride 12.5%w/v. A novel single-step process gelation for the extemporaneous gelation of loaded oral systems has been therefore developed. These technologically advanced formulations showed high printing reproducibility in manufacturing different models (mass of a single layer 535.41 ± 40.00 mg with an average drug loading efficiency of 85% w/w) and similar release behavior, paving the way for their customization in terms of drug dosages via this pioneering process.
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http://dx.doi.org/10.1016/j.carbpol.2021.117791DOI Listing
May 2021

TFF1 Induces Aggregation and Reduces Motility of .

Int J Mol Sci 2021 Feb 12;22(4). Epub 2021 Feb 12.

Department of Pharmacy, University of Salerno, 84084 Fisciano (SA), Italy.

Gastric cancer is considered one of the most common malignancies in humans and infection is the major environmental risk factor of gastric cancer development. Given the high spread of this bacterium whose infection is mostly asymptomatic, colonization persists for a long time, becoming chronic and predisposing to malignant transformation. The first defensive barrier from bacterial infection is constituted by the gastric mucosa that secretes several protective factors, among which is the trefoil factor 1 (TFF1), that, as mucin 5AC, binds the bacterium. Even if the protective role of TFF1 is well-documented, the molecular mechanisms that confer a beneficial function to the interaction among TFF1 and remain still unclear. Here we analyze the effects of this interaction on at morphological and molecular levels by means of microscopic observation, chemiotaxis and motility assays and real-time PCR analysis. Our results show that TFF1 favors aggregation of and significantly slows down the motility of the bacterium across the mucus. Such aggregates significantly reduce both and gene transcription compared with bacteria not incubated with TFF1. Finally, our results suggest that the interaction between TFF1 and the bacterium may explain the frequent persistence of in the human host without inducing disease.
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http://dx.doi.org/10.3390/ijms22041851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918695PMC
February 2021

Special Issue: Biopolymers in Drug Delivery and Regenerative Medicine.

Molecules 2021 Jan 22;26(3). Epub 2021 Jan 22.

Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I+D Farma Group (GI-1645), Faculty of Pharmacy and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.

Biopolymers and biocomposites have emerged as promising pathways to develop novel materials and substrates for biomedical applications [...].
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http://dx.doi.org/10.3390/molecules26030568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865344PMC
January 2021

Testing the identification effectiveness of an unknown outbreak of the Infectious Diseases Seeker (IDS) using and comparing the novel coronavirus disease (COVID-19) outbreak with the past SARS and MERS epidemics.

J Infect Public Health 2021 Jan 9;14(1):123-130. Epub 2020 Dec 9.

Department of Industrial Engineering, University of Rome "Tor Vergata", Italy.

Background: The aim of this research is to assess the predictive accuracy of the Infectious Diseases Seeker (IDS) - an innovative tool for prompt identification of the causative agent of infectious diseases during outbreaks - when field epidemiological data collected from a novel outbreak of unknown origin are analysed by the tool. For this reason, it has been taken into account the novel coronavirus disease (COVID-19) outbreak, which began in China at the end of December 2019, has rapidly spread around the globe, and it has led to a public health emergency of international concern (PHEIC), declared to the 30th of January 2020 by the World Health Organization (WHO).

Methods: The IDS takes advantage of an off-line database, built before the COVID-19 pandemic, which represents a pivotal characteristic for working without an internet connection. The software has been tested using the epidemiological data available in different and progressive stages of the COVID-19 outbreak. As a comparison, the results of the tests performed using the epidemiological data from the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) epidemic in 2002 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) epidemic in 2012, are shown.

Results: The overall outcomes provided by the software are comforting, as a matter of the fact that IDS has identified with a good accuracy the SARS and MERS epidemics (over 90%), while, as expected, it has not provided erroneous and equivocal readings after the elaboration COVID-19 epidemic data.

Conclusions: Even though IDS has not recognized the COVID-19 epidemic, it has not given to the end user a false result and wrong interpretation, as expected by the developers. For this reason, IDS reveals itself as useful software to identify a possible epidemic or outbreak. Thus, the intention of developers is to plan, once the software will be released, dedicated updates and upgrades of the database (e.g., SARS-CoV-2) in order to keep this tool increasingly useful and applicable to reality.
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http://dx.doi.org/10.1016/j.jiph.2020.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725062PMC
January 2021

Plant Roots Release Small Extracellular Vesicles with Antifungal Activity.

Plants (Basel) 2020 Dec 15;9(12). Epub 2020 Dec 15.

Institute of Biosciences and BioResources, Research Division Naples, National Research Council, 80131 Naples, Italy.

Extracellular Vesicles (EVs) play pivotal roles in cell-to-cell and inter-kingdom communication. Despite their relevant biological implications, the existence and role of plant EVs released into the environment has been unexplored. Herein, we purified round-shaped small vesicles (EVs) by differential ultracentrifugation of a sampling solution containing root exudates of hydroponically grown tomato plants. Biophysical analyses, by means of dynamic light scattering, microfluidic resistive pulse sensing and scanning electron microscopy, showed that the size of root-released EVs range in the nanometric scale (50-100 nm). Shot-gun proteomics of tomato EVs identified 179 unique proteins, several of which are known to be involved in plant-microbe interactions. In addition, the application of root-released EVs induced a significant inhibition of spore germination and of germination tube development of the plant pathogens , and Interestingly, these EVs contain several proteins involved in plant defense, suggesting that they could be new components of the plant innate immune system.
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http://dx.doi.org/10.3390/plants9121777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765200PMC
December 2020

On the Potential of Time Delay Neural Networks to Detect Indirect Coupling between Time Series.

Entropy (Basel) 2020 May 21;22(5). Epub 2020 May 21.

Department of Industrial Engineering, University of Rome "Tor Vergata", via del Politecnico 1, 00100 Roma, Italy.

Determining the coupling between systems remains a topic of active research in the field of complex science. Identifying the proper causal influences in time series can already be very challenging in the trivariate case, particularly when the interactions are non-linear. In this paper, the coupling between three Lorenz systems is investigated with the help of specifically designed artificial neural networks, called time delay neural networks (TDNNs). TDNNs can learn from their previous inputs and are therefore well suited to extract the causal relationship between time series. The performances of the TDNNs tested have always been very positive, showing an excellent capability to identify the correct causal relationships in absence of significant noise. The first tests on the time localization of the mutual influences and the effects of Gaussian noise have also provided very encouraging results. Even if further assessments are necessary, the networks of the proposed architecture have the potential to be a good complement to the other techniques available in the market for the investigation of mutual influences between time series.
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http://dx.doi.org/10.3390/e22050584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517103PMC
May 2020

Upgrading Model Selection Criteria with Goodness of Fit Tests for Practical Applications.

Entropy (Basel) 2020 Apr 15;22(4). Epub 2020 Apr 15.

Department of Industrial Engineering, University of Rome "Tor Vergata", via del Politecnico 1, 01100 Roma, Italy.

The Bayesian information criterion (BIC), the Akaike information criterion (AIC), and some other indicators derived from them are widely used for model selection. In their original form, they contain the likelihood of the data given the models. Unfortunately, in many applications, it is practically impossible to calculate the likelihood, and, therefore, the criteria have been reformulated in terms of descriptive statistics of the residual distribution: the variance and the mean-squared error of the residuals. These alternative versions are strictly valid only in the presence of additive noise of Gaussian distribution, not a completely satisfactory assumption in many applications in science and engineering. Moreover, the variance and the mean-squared error are quite crude statistics of the residual distributions. More sophisticated statistical indicators, capable of better quantifying how close the residual distribution is to the noise, can be profitably used. In particular, specific goodness of fit tests have been included in the expressions of the traditional criteria and have proved to be very effective in improving their discriminating capability. These improved performances have been demonstrated with a systematic series of simulations using synthetic data for various classes of functions and different noise statistics.
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http://dx.doi.org/10.3390/e22040447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516921PMC
April 2020

Quantifying Total Influence between Variables with Information Theoretic and Machine Learning Techniques.

Entropy (Basel) 2020 Jan 24;22(2). Epub 2020 Jan 24.

Associazione EURATOM-ENEA, University of Rome "Tor Vergata", 00133 Rome, Italy.

The increasingly sophisticated investigations of complex systems require more robust estimates of the correlations between the measured quantities. The traditional Pearson correlation coefficient is easy to calculate but sensitive only to linear correlations. The total influence between quantities is, therefore, often expressed in terms of the mutual information, which also takes into account the nonlinear effects but is not normalized. To compare data from different experiments, the information quality ratio is, therefore, in many cases, of easier interpretation. On the other hand, both mutual information and information quality ratio are always positive and, therefore, cannot provide information about the sign of the influence between quantities. Moreover, they require an accurate determination of the probability distribution functions of the variables involved. As the quality and amount of data available are not always sufficient to grant an accurate estimation of the probability distribution functions, it has been investigated whether neural computational tools can help and complement the aforementioned indicators. Specific encoders and autoencoders have been developed for the task of determining the total correlation between quantities related by a functional dependence, including information about the sign of their mutual influence. Both their accuracy and computational efficiencies have been addressed in detail, with extensive numerical tests using synthetic data. A careful analysis of the robustness against noise has also been performed. The neural computational tools typically outperform the traditional indicators in practically every respect.
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http://dx.doi.org/10.3390/e22020141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516551PMC
January 2020

Technologies and Formulation Design of Polysaccharide-Based Hydrogels for Drug Delivery.

Molecules 2020 Jul 10;25(14). Epub 2020 Jul 10.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy.

Polysaccharide-based hydrogel particles (PbHPs) are very promising carriers aiming to control and target the release of drugs with different physico-chemical properties. Such delivery systems can offer benefits through the proper encapsulation of many drugs (non-steroidal and steroidal anti-inflammatory drugs, antibiotics, etc) ensuring their proper release and targeting. This review discusses the different phases involved in the production of PbHPs in pharmaceutical technology, such as droplet formation (SOL phase), sol-gel transition of the droplets (GEL phase) and drying, as well as the different methods available for droplet production with a special focus on prilling technique. In addition, an overview of the various droplet gelation methods with particular emphasis on ionic cross-linking of several polysaccharides enabling the formation of particles with inner highly porous network or nanofibrillar structure is given. Moreover, a detailed survey of the different inner texture, in xerogels, cryogels or aerogels, each with specific arrangement and properties, which can be obtained with different drying methods, is presented. Various case studies are reported to highlight the most appropriate application of such systems in pharmaceutical field. We also describe the challenges to be faced for the breakthrough towards clinic studies and, finally, the market, focusing on the useful approach of safety-by-design (SbD).
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http://dx.doi.org/10.3390/molecules25143156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397281PMC
July 2020

Enhancing Radiation Detection by Drones through Numerical Fluid Dynamics Simulations.

Sensors (Basel) 2020 Mar 23;20(6). Epub 2020 Mar 23.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.

This study addresses the optimization of the location of a radioactive-particle sensor on a drone. Based on the analysis of the physical process and of the boundary conditions introduced in the model, computational fluid dynamics simulations were performed to analyze how the turbulence caused by drone propellers may influence the response of the sensors. Our initial focus was the detection of a small amount of radioactivity, such as that associated with a release of medical waste. Drones equipped with selective low-cost sensors could be quickly sent to dangerous areas that first responders might not have access to and be able to assess the level of danger in a few seconds, providing details about the source terms to Radiological-Nuclear (RN) advisors and decision-makers. Our ultimate application is the simulation of complex scenarios where fluid-dynamic instabilities are combined with elevated levels of radioactivity, as was the case during the Chernobyl and Fukushima nuclear power plant accidents. In similar circumstances, accurate mapping of the radioactive plume would provide invaluable input-data for the mathematical models that can predict the dispersion of radioactivity in time and space. This information could be used as input for predictive models and decision support systems (DSS) to get a full situational awareness. In particular, these models may be used either to guide the safe intervention of first responders or the later need to evacuate affected regions.
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http://dx.doi.org/10.3390/s20061770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147154PMC
March 2020

Design and Development of Spray-Dried Microsystems to Improve Technological and Functional Properties of Bioactive Compounds from Hazelnut Shells.

Molecules 2020 Mar 11;25(6). Epub 2020 Mar 11.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano (SA), Italy.

An extract obtained from hazelnut shells by-products (HSE) has antioxidant and chemopreventive effects on human melanoma and cervical cancer cell lines, inducing apoptosis by caspase-3 activation. A clinical translation is limited by poor water solubility and low bioavailability. Dried plant extracts often show critical characteristics such as sticky/gummy appearance, unpleasant smell, and instability involving practical difficulties in processing for industrial use. A spray drying method has been applied to transform raw HSE in a microparticulate powder. The biopolymeric matrix was based on l-proline as loading carrier, hydroxyethylcellulose in combination with pectin as coating polymers; lecithin and ethanol were used as solubility enhancers. A Hot-Cold-Hot method was selected to prepare the liquid feed. The thus prepared powder showed good technological properties (solid-state, particle dimensions, morphology, and water dissolution rate), stability, and unchanged chemopreventive effects with respect to the unprocessed HSE.
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http://dx.doi.org/10.3390/molecules25061273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144004PMC
March 2020

Zinc and Calcium Cations Combination in the Production of Floating Alginate Beads as Prednisolone Delivery Systems.

Molecules 2020 Mar 4;25(5). Epub 2020 Mar 4.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy.

The aim of this research was to verify the application of alginate in combination with Ca and Zn ions to produce a floating and prolonged release system for the oral administration of prednisolone. Hollow and floating gel-beads were designed using prilling/ionotropic gelation as the microencapsulation technique, zinc acetate in the gelling solution as the alginate external crosslinker, and calcium carbonate in the feed as the internal crosslinking agent able to generate gas when in contact with the acidic zinc acetate solution. To achieve this goal, drug/alginate solutions were opportunely combined with different amounts of calcium carbonate. The effect of the addition of calcium carbonate into the feed solution on buoyancy, encapsulation efficiency, morphology, size distribution, as well as in vitro drug release profile of the alginate particles was studied. Moreover, the ability of the floating beads to modulate in vivo the anti-inflammatory response was assayed using the carrageenan-induced acute oedema in rat paw. The proposed strategy allowed obtaining alginate beads with extremely high encapsulation efficiency values (up to 94%) and a very porous inner matrix conferring buoyancy in vitro in simulated gastric fluid up to 5 h. Moreover, in vivo, the best formulation, F4, resulted in the ability to prolong the anti-inflammatory effect up to 15 h compared with raw prednisolone.
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http://dx.doi.org/10.3390/molecules25051140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179156PMC
March 2020

Pectin and Zinc Alginate: The Right Inner/Outer Polymer Combination for Core-Shell Drug Delivery Systems.

Pharmaceutics 2020 Jan 21;12(2). Epub 2020 Jan 21.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy.

Core-shell beads loaded with betamethasone were developed using co-axial prilling as production technique and pectin plus alginate as polymeric carriers. During this study, many operative conditions were intensively investigated to find the best ones necessary to produce uniform core-shell particle systems in a reproducible way. Particularly, feed solutions' composition, polymers mass ratios and the effect of the main process parameters on particles production, micromeritics, inner structure, drug loading and drug-release/swelling profiles in simulated biological fluids were studied. The optimized core-shell formulation F5 produced with a pectin core concentration of 4.0% and an alginate shell concentration of 2.0% (2:1 core:shell ratio) acted as a sustained drug delivery system. It was able to reduce the early release of the drug in the upper part of the gastro-intestinal tract for the presence of the zinc-alginate gastro-resistant outer layer and to specifically deliver it in the colon, thanks to the selectivity of amidated low methoxy pectin core for this district. Therefore, these particles may be proposed as colon targeted drug delivery systems useful for inflammatory bowel disease (IBD) therapy.
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http://dx.doi.org/10.3390/pharmaceutics12020087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076462PMC
January 2020

In situ gelling alginate-pectin blend particles loaded with Ac2-26: A new weapon to improve wound care armamentarium.

Carbohydr Polym 2020 Jan 9;227:115305. Epub 2019 Sep 9.

Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.

In this paper, alginate-pectin blend particles loaded with Annexin A1 derived peptide Ac2-26 as an in situ forming dressing was successfully developed for wound repair applications. High mannuronic (M) content alginate and amidated pectin blend have been used to encapsulate Ac2-26 in order to enhance stability of the peptide at room temperature and to control its release through the in situ formed gel. Ac2-26 recovery and FTIR studies suggests chemical interactions between peptide and polysaccharides blend able to improve the encapsulation efficiency of Ac2-26 into the polymer matrix and control its release, till 48 h. In vitro wound healing assay on HaCaT cells highlights the ability of Ac2-26 to significantly accelerate wound healing compared to unloaded particles, with complete closure of the wound model in 24 h. Therefore, all these results suggest that Ac2-26 loaded submicrometric in situ gelling powders could be a promising wound dressing to improve wound care armamentarium.
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http://dx.doi.org/10.1016/j.carbpol.2019.115305DOI Listing
January 2020

An Opinion Paper on Aerogels for Biomedical and Environmental Applications.

Molecules 2019 May 10;24(9). Epub 2019 May 10.

Institute of Thermal Separation Processes, Hamburg University of Technology, Eißendorfer Straße 38, 21073 Hamburg, Germany.

Aerogels are a special class of nanostructured materials with very high porosity and tunable physicochemical properties. Although a few types of aerogels have already reached the market in construction materials, textiles and aerospace engineering, the full potential of aerogels is still to be assessed for other technology sectors. Based on current efforts to address the material supply chain by a circular economy approach and longevity as well as quality of life with biotechnological methods, environmental and life science applications are two emerging market opportunities where the use of aerogels needs to be further explored and evaluated in a multidisciplinary approach. In this opinion paper, the relevance of the topic is put into context and the corresponding current research efforts on aerogel technology are outlined. Furthermore, key challenges to be solved in order to create materials by design, reproducible process technology and society-centered solutions specifically for the two abovementioned technology sectors are analyzed. Overall, advances in aerogel technology can yield innovative and integrated solutions for environmental and life sciences which in turn can help improve both the welfare of population and to move towards cleaner and smarter supply chain solutions.
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http://dx.doi.org/10.3390/molecules24091815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539078PMC
May 2019

On the Use of Entropy to Improve Model Selection Criteria.

Entropy (Basel) 2019 Apr 12;21(4). Epub 2019 Apr 12.

Department of Industrial Engineering, University of Rome "Tor Vergata", 00133 Roma, Italy.

The most widely used forms of model selection criteria, the Bayesian Information Criterion (BIC) and the Akaike Information Criterion (AIC), are expressed in terms of synthetic indicators of the residual distribution: the variance and the mean-squared error of the residuals respectively. In many applications in science, the noise affecting the data can be expected to have a Gaussian distribution. Therefore, at the same level of variance and mean-squared error, models, whose residuals are more uniformly distributed, should be favoured. The degree of uniformity of the residuals can be quantified by the Shannon entropy. Including the Shannon entropy in the BIC and AIC expressions improves significantly these criteria. The better performances have been demonstrated empirically with a series of simulations for various classes of functions and for different levels and statistics of the noise. In presence of outliers, a better treatment of the errors, using the Geodesic Distance, has proved essential.
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http://dx.doi.org/10.3390/e21040394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7514877PMC
April 2019

Design of Aerogels, Cryogels and Xerogels of Alginate: Effect of Molecular Weight, Gelation Conditions and Drying Method on Particles' Micromeritics.

Molecules 2019 Mar 17;24(6). Epub 2019 Mar 17.

Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy.

Processing and shaping of dried gels are of interest in several fields like alginate aerogel beads used as highly porous and nanostructured particles in biomedical applications. The physicochemical properties of the alginate source, the solvent used in the gelation solution and the gel drying method are key parameters influencing the characteristics of the resulting dried gels. In this work, dried gel beads in the form of xerogels, cryogels or aerogels were prepared from alginates of different molecular weights (120 and 180 kDa) and concentrations (1.25, 1.50, 2.0 and 2.25% (/)) using different gelation conditions (aqueous and ethanolic CaCl₂ solutions) and drying methods (supercritical drying, freeze-drying and oven drying) to obtain particles with a broad range of physicochemical and textural properties. The stability of physicochemical properties of alginate aerogels under storage conditions of 25 °C and 65% relative humidity (ICH-climatic zone II) during 1 and 3 months was studied. Results showed significant effects of the studied processing parameters on the resulting alginate dried gel properties. Stability studies showed small variations in aerogels weight and specific surface area after 3 months of storage, especially, in the case of aerogels produced with medium molecular weight alginate.
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http://dx.doi.org/10.3390/molecules24061049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6471992PMC
March 2019

Poly(vinyl alcohol) 3D printed tablets: The effect of polymer particle size on drug loading and process efficiency.

Int J Pharm 2019 Apr 25;561:1-8. Epub 2019 Feb 25.

Department of Pharmacy, University of Salerno, Fisciano, SA, Italy. Electronic address:

Fused deposition modeling by 3D-printing is a rapid technique for the production of personalized drug dosage forms. One of the most delicate step of the whole process is the drug loading onto the thermoplastic polymer to obtain the drug-loaded filament used as feedstock for 3D FDM printers. With the aim of improving the drug loading, a systematic study on the influence of polymer size distribution on the quantity of drug able to adhere onto the polymer surface was conducted. Several solid mixtures were prepared, using five PVA batches (4000-5000 µm, 1000-2000 µm, 600-1000 µm, 250-600 µm, <250 µm) and Ciprofloxacin hydrochloride as active compound in different ratios. Operative specifics and printer's parameters were tuned for an optimal print of drug-loaded filaments into the desired dosage forms, i.e. cylindrical printlets, fully characterized in terms of homogeneity, process efficiency, physical properties, drug content and release kinetics. The PVA particle size affected the polymer ability to form homogeneous mixture with the drug and the efficiency of the extrusion process. In particular, finest PVA batches showed better processability and reduced the drug loss during the drug/polymer mixing and the extrusion process. Drug-loaded filaments with different drug concentrations were successfully printed and the obtained printlets dissolution profiles were almost superimposable, taking an important step for the future application of 3D-printing manufacturing process to obtain personalized galenic formulations.
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http://dx.doi.org/10.1016/j.ijpharm.2019.02.025DOI Listing
April 2019

Physiochemical and protein datasets related to citrus juice sac cells-derived nanovesicles and microvesicles.

Data Brief 2019 Feb 13;22:251-254. Epub 2018 Dec 13.

MS Proteomics Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Hungary.

Qualitative and quantitative data obtained on micro and nanovesicle enriched fractions isolated from four citrus species, , , and are presented. It includes physiochemical characterization by transmission electron microscopy (TEM) and dynamic laser scattering (DLS); and molecular characterization of the biocargo of citrus vesicles by quantitative label-free proteomics. Vesicular transport related proteins of were predicted by (i) finding orthologues based on previously described vesicular transport proteins and (ii) GO term enrichment analysis. Based on the protein content different types of intra and intercellular vesicles were dissected and the distribution of different Enzyme classes (ECs) were determined. This data article is related to "Protein biocargo of citrus fruit-derived vesicles reveals heterogeneous transport and extracellular vesicle populations" (Pocsfalvi et al., 2018).
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http://dx.doi.org/10.1016/j.dib.2018.12.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305887PMC
February 2019

On the Use of Transfer Entropy to Investigate the Time Horizon of Causal Influences between Signals.

Entropy (Basel) 2018 Aug 22;20(9). Epub 2018 Aug 22.

Associazione EUROfusion-University of Rome "Tor Vergata", Via Orazio Raimondo, 18, 00173 Roma, Italy.

Understanding the details of the correlation between time series is an essential step on the route to assessing the causal relation between systems. Traditional statistical indicators, such as the Pearson correlation coefficient and the mutual information, have some significant limitations. More recently, transfer entropy has been proposed as a powerful tool to understand the flow of information between signals. In this paper, the comparative advantages of transfer entropy, for determining the time horizon of causal influence, are illustrated with the help of synthetic data. The technique has been specifically revised for the analysis of synchronization experiments. The investigation of experimental data from thermonuclear plasma diagnostics proves the potential and limitations of the developed approach.
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http://dx.doi.org/10.3390/e20090627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513156PMC
August 2018

Protein biocargo of citrus fruit-derived vesicles reveals heterogeneous transport and extracellular vesicle populations.

J Plant Physiol 2018 Oct 21;229:111-121. Epub 2018 Jul 21.

MS Proteomics Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Hungary.

Cell-derived vesicles are membrane-enclosed organelles that transport material inside and outside the cell. Plant-derived vesicles are receiving more and more attention due to their potential as nanovectors for the delivery of biologically active substances. Here, we studied the heterogeneity and protein biocargo in citrus fruit juice sac cell-derived vesicles populations. Micro- and nano-sized vesicle fractions were isolated from four citrus species, C. sinensis, C. limon, C. paradisi and C. aurantium, characterized using physicochemical methods and protein cargos were compared using label-free quantitative shotgun proteomics. In each sample approximately 600-800 proteins were identified. Orthologues of most of the top-ranking proteins have previously been reported in extracellular vesicles of mammalian origin. High expression levels of patellin-3-like, clathrin heavy chain, heat shock proteins, 14-3-3 protein, glyceraldehyde-3-phosphate dehydrogenase and fructose-bisphosphate aldolase 6 were measured in all samples while aquaporin was highly expressed only in the nanovesicle fractions. Bioinformatics revealed more than hundred protein orthologues potentially implicated in vesicular trafficking. In particular, the presence of CCV, COPI and COPII coat proteins indicates the presence of heterogeneous populations of intracellular transport vesicles. Moreover, a high number of different enzymes including hydrolases and oxidoreductases are ubiquities in citrus fruit sac cell-derived vesicles.
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http://dx.doi.org/10.1016/j.jplph.2018.07.006DOI Listing
October 2018

A novel method for the production of core-shell microparticles by inverse gelation optimized with artificial intelligent tools.

Int J Pharm 2018 Mar 16;538(1-2):97-104. Epub 2018 Jan 16.

Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132 I-84084 Fisciano, SA, Italy. Electronic address:

Numerous studies have been focused on hydrophobic compounds encapsulation as oils. In fact, oils can provide numerous health benefits as synergic ingredient combined with other hydrophobic active ingredients. However, stable microparticles for pharmaceutical purposes are difficult to achieve when commonly techniques are used. In this work, sunflower oil was encapsulated in calcium-alginate capsules by prilling technique in co-axial configuration. Core-shell beads were produced by inverse gelation directly at the nozzle using a w/o emulsion containing aqueous calcium chloride solution in sunflower oil pumped through the inner nozzle while an aqueous alginate solution, coming out from the annular nozzle, produced the beads shell. To optimize process parameters artificial intelligence tools were proposed to optimize the numerous prilling process variables. Homogeneous and spherical microcapsules with narrow size distribution and a thin alginate shell were obtained when the parameters as w/o constituents, polymer concentrations, flow rates and frequency of vibration were optimized by two commercial software, FormRules® and INForm®, which implement neurofuzzy logic and Artificial Neural Networks together with genetic algorithms, respectively. This technique constitutes an innovative approach for hydrophobic compounds microencapsulation.
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http://dx.doi.org/10.1016/j.ijpharm.2018.01.023DOI Listing
March 2018

Clarithromycin and N-acetylcysteine co-spray-dried powders for pulmonary drug delivery: A focus on drug solubility.

Int J Pharm 2017 Nov 1;533(2):463-469. Epub 2017 Apr 1.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano (SA), Italy. Electronic address:

Cystic fibrosis (CF) lungs are usually susceptible to Pseudomonas aeruginosa colonization and this bacterium is resistant to immune system clearance and drug control. Particularly, the biofilm mode of growth protects several microorganisms from host defenses and antibacterial drugs, mainly due to a delayed penetration of the drug through the biofilm matrix. Biofilm, together with lung mucus viscosity and tenacity, reduces, therefore, the effectiveness of conventional antibiotic therapy in CF. The aim of this research was to design and develop a stable, portable, easy to use dry powder inhaler (DPI) for CF patients, able to release directly to the lung an association of macrolide antibiotics (clarithromycin) and a mucolytic agent (N-Acetyl-Cysteine). Its effectiveness is based on the counteracting of the characteristics of P. aeruginosa infections in CF (lung bacterial adhesion to lung epithelium, biofilm formation and mucus viscosity) and the ability to let the antimicrobial drug exert their pharmacological action. A solution of these two drugs, without any excipients, was spray-dried to obtain respirable microparticles, characterized by aerodynamic diameters suitable for inhalation (<5.0μm). The morphology evaluation evidenced particles shape dependent on water content in the spray drying feeds, with wrinkled particles more evident with higher water content. Moreover, thanks to the presence of N-acetylcysteine which can interact with clarithromycin dimethyl-amino group, a consistent enhancement of drug solubility was obtained, compared to raw material and to the drug sprayed alone. The mucolytic agent added in the DPI may improve the macrolide diffusion into the mucus, enabling its action.
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http://dx.doi.org/10.1016/j.ijpharm.2017.03.079DOI Listing
November 2017

Submicrometric hypromellose acetate succinate particles as carrier for soy isoflavones extract with improved skin penetration performance.

Carbohydr Polym 2017 Jun 8;165:22-29. Epub 2017 Feb 8.

Department of Pharmacy, University of Salerno, via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.

In this study, hypromellose acetate succinate (HPMCAS) stable submicronic particles loaded with a soy isoflavones extract have been obtained by nano spray drying technology. HPMCAS has been used as excipient able to increase both stability and supersaturation levels of the active ingredients hence able to enhance skin penetration performance of genistein and daidzein. The influence of polymer/extract ratio as other process variables, on particle size, morphology and permeation performance, have been investigated. Particles in submicronic range (mean size around 550nm) and narrow size distribution with high encapsulation efficiency (up to 86%) were obtained. HPMCAS was able to improve amorphization of genistein during the atomization process and avoid recrystallization during storage, even in harsh environmental condition. Moreover, the enhanced affinity of the optimized formulations with aqueous media, strongly increased isoflavones penetration through membrane with diffusive properties well-correlated to human skin, up to 10-fold higher than pure soy isoflavones extract raw material.
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http://dx.doi.org/10.1016/j.carbpol.2017.02.025DOI Listing
June 2017

Synergistic effect of divalent cations in improving technological properties of cross-linked alginate beads.

Int J Biol Macromol 2017 Aug 18;101:100-106. Epub 2017 Mar 18.

Department of Pharmacy, University of Salerno, I-84084 Fisciano, SA, Italy. Electronic address:

Gelling solution parameters are some of the most important variables in ionotropic gelation and consequently influence the technological characteristics of the product. To date, only a few studies have focused on the simultaneous use of multiple cations as gelling agents. With the aim to deeply explore this possibility, in this research we investigated the effect of two divalent cations (Ca and Zn) on alginate beads formation and properties. Alginate beads containing prednisolone (P) as model drug were prepared by prilling technique. The main critical variables of the ionotropic gelation process i.e. composition of the aqueous feed solutions (sodium alginate and prednisolone concentration) and cross-linking conditions (Ca, Zn or Ca+Zn), were studied. The obtained beads were characterized and their in vitro release performances were assessed in conditions simulating the gastrointestinal environment. Results evidenced a synergistic effect of the two cations, affecting positively both the encapsulation efficiency and the ability of the alginate polymeric matrix to control the drug release. A Ca/Zn ratio of 4:1, in fact, exploited the Ca ability of establish quicker electrostatic interactions with guluronic groups of alginate and the Zn ability to establish covalent-like bonds with carboxylate groups of both guluronic and mannuronic moieties of alginate.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.03.077DOI Listing
August 2017

Hazelnut (Corylus avellana L.) Shells Extract: Phenolic Composition, Antioxidant Effect and Cytotoxic Activity on Human Cancer Cell Lines.

Int J Mol Sci 2017 Feb 13;18(2). Epub 2017 Feb 13.

Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, I-84084 Fisciano (SA), Italy.

Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract). Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%-2.93%, /). The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (EC = 31.7 μg/mL with respect to α-tocopherol EC = 10.1 μg/mL), and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC = 584, 459, and 526 μg/mL, respectively). The expression of cleaved forms of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28) and human cervical cancer (HeLa) cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin), and phenol derivatives (gallic acid), showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.
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http://dx.doi.org/10.3390/ijms18020392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343927PMC
February 2017

Prednisolone Delivery Platforms: Capsules and Beads Combination for a Right Timing Therapy.

PLoS One 2016 29;11(7):e0160266. Epub 2016 Jul 29.

Department of Pharmacy, University of Salerno, Fisciano, Italy.

In this work, a platform of alginate beads loaded with Prednisolone in hypromellose/gellan gum capsules (F6/Cps) able to delay steroidal anti-inflammatory drug (SAID) release as needed for chronotherapy of rheumatoid arthritis is proposed. Rheumatoid arthritis, showing a worsening in symptoms in the morning upon waking, is a pathology that can benefit from chronotherapy. With the aim to maximize prednisolone therapeutic action allowing the right timing of glucocorticoid therapy, different engineered microparticles (gel-beads) were manufactured using prilling (laminar jet break-up) as micro-encapsulation technique and Zn-alginate as gastroresistant carrier. Starting from various feed solutions and process parameters, the effect of the variables on particles size, morphology, solid state properties and drug release was studied. The optimization of operative and prilling/ionotropic gelation variables led to microspheres with almost spherical shape and a narrow dimensional range. The feed solution with the highest alginate (2.5% w/v) amount and drug/polymer ratio (1:5 w/w) gave rise to the highest encapsulation efficiency (78.5%) as in F6 formulation. As to drug release, F6 exhibited an interesting dissolution profile, releasing about 24% of the drug in simulated gastric fluid followed by a more sustained profile in simulated intestinal fluid. #F6, acting as a gastro-resistant and delayed release formulation, was selected for in vivo studies on male Wistar rats by means of a carrageenan-induced oedema model. Finally, this efficacious formulation was used as core material for the development of a final dosage form: F6/Cps allowed to significantly reduce prednisolone release in simulated gastric fluid (12.6%) and delayed drug release up to about 390 minutes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160266PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966952PMC
August 2017

Nanospray Drying as a Novel Tool to Improve Technological Properties of Soy Isoflavone Extracts.

Planta Med 2017 Mar 24;83(5):426-433. Epub 2016 Jun 24.

Department of Pharmacy, University of Salerno, Fisciano, SA, Italy.

Pharmacological evidences have correlated a low incidence of osteoporosis, breast cancer, cardiovascular disease, and colon cancer in Asian populations, high consumers of soya, to the properties of soy isoflavones, more specifically to daidzein and genistein. However, in spite of the potent biological activity, their poor water solubility has a strong negative effect on bioavailability. In this study, an innovative technique, nano spray drying, was used to obtain nanoparticles loaded with a soybean dry extract while carboxymethyl cellulose was used as the excipient. The optimization of the process conditions allowed for the manufacturing of stable nanoparticles with a mean size of around 650 nm, a narrow size distribution, and a high encapsulation efficiency (between 78 % and 89 %). The presence of carboxymethyl cellulose was able to stabilize the isoflavone extract and enhance its affinity with aqueous media, strongly increasing its permeation through biological membranes up to 4.5-fold higher than pure soy isoflavone extract raw material and twice its homologous minispray-dried formulation. These results are very useful for the administration of the extract, either topically or orally, suggesting that the isoflanones extract nanoparticulate powder obtained by nano spray drying has great potential to enhance extract bioavailability and could be used as an ingredient to be enclosed in dietary supplements and nutraceutical and cosmeceutical products.
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http://dx.doi.org/10.1055/s-0042-110179DOI Listing
March 2017

Biological Dual-Use Research and Synthetic Biology of Yeast.

Sci Eng Ethics 2017 04 20;23(2):365-374. Epub 2016 Jun 20.

Department of Biology and Biotechnology, La Sapienza University of Rome, Rome, Italy.

In recent years, the publication of the studies on the transmissibility in mammals of the H5N1 influenza virus and synthetic genomes has triggered heated and concerned debate within the community of scientists on biological dual-use research; these papers have raised the awareness that, in some cases, fundamental research could be directed to harmful experiments, with the purpose of developing a weapon that could be used by a bioterrorist. Here is presented an overview regarding the dual-use concept and its related international agreements which underlines the work of the Australia Group (AG) Export Control Regime. It is hoped that the principles and activities of the AG, that focuses on export control of chemical and biological dual-use materials, will spread and become well known to academic researchers in different countries, as they exchange biological materials (i.e. plasmids, strains, antibodies, nucleic acids) and scientific papers. To this extent, and with the aim of drawing the attention of the scientific community that works with yeast to the so called Dual-Use Research of Concern, this article reports case studies on biological dual-use research and discusses a synthetic biology applied to the yeast Saccharomyces cerevisiae, namely the construction of the first eukaryotic synthetic chromosome of yeast and the use of yeast cells as a factory to produce opiates. Since this organism is considered harmless and is not included in any list of biological agents, yeast researchers should take simple actions in the future to avoid the sharing of strains and advanced technology with suspicious individuals.
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http://dx.doi.org/10.1007/s11948-016-9774-1DOI Listing
April 2017