Publications by authors named "Pasquale Gaudio"

67 Publications

Post-COVID Syndrome: The Research Progress in the Treatment of Pulmonary after COVID-19 Infection.

Pharmaceutics 2022 May 26;14(6). Epub 2022 May 26.

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

Post-COVID syndrome or is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection, the pathogen responsible for coronavirus disease. The content herein presented reviews the reported long-term consequences and aftereffects of COVID-19 infection and the potential strategies to adopt for their management. Recent studies have shown that severe forms of COVID-19 can progress into acute respiratory distress syndrome (ARDS), a predisposing factor of pulmonary fibrosis that can irreversibly compromise respiratory function. Considering that the most serious complications are observed in the airways, the inhalation delivery of drugs directly to the lungs should be preferred, since it allows to lower the dose and systemic side effects. Although further studies are needed to optimize these techniques, recent studies have also shown the importance of in vitro models to recreate the SARS-CoV-2 infection and study its sequelae. The information reported suggests the necessity to develop new inhalation therapies in order to improve the quality of life of patients who suffer from this condition.
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http://dx.doi.org/10.3390/pharmaceutics14061135DOI Listing
May 2022

CRS Italia: drug delivery and translational research activities.

Drug Deliv Transl Res 2022 Jun 10. Epub 2022 Jun 10.

Laboratory of Nanotechnology for Precision Medicine, Italian Institute of Technology, Genova, Italy.

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http://dx.doi.org/10.1007/s13346-022-01195-6DOI Listing
June 2022

One-Step Fabrication of Novel Polyethersulfone-Based Composite Electrospun Nanofiber Membranes for Food Industry Wastewater Treatment.

Membranes (Basel) 2022 Apr 11;12(4). Epub 2022 Apr 11.

Sanitary Environmental Engineering Division (SEED), Department of Civil Engineering, University of Salerno, 84084 Fisciano, Italy.

Using an environmentally friendly approach for eliminating methylene blue from an aqueous solution, the authors developed a unique electrospun nanofiber membrane made of a combination of polyethersulfone and hydroxypropyl cellulose (PES/HPC). SEM results confirmed the formation of a uniformly sized nanofiber membrane with an ultrathin diameter of 168.5 nm (for PES/HPC) and 261.5 nm (for pristine PES), which can be correlated by observing the absorption peaks in FTIR spectra and their amorphous/crystalline phases in the XRD pattern. Additionally, TGA analysis indicated that the addition of HPC plays a role in modulating their thermal stability. Moreover, the blended nanofiber membrane exhibited better mechanical strength and good hydrophilicity (measured by the contact angle). The highest adsorption capacity was achieved at a neutral pH under room temperature (259.74 mg/g), and the pseudo-second-order model was found to be accurate. In accordance with the Langmuir fitted model and MB adsorption data, it was revealed that the adsorption process occurred in a monolayer form on the membrane surface. The adsorption capacity of the MB was affected by the presence of various concentrations of NaCl (0.1-0.5 M). The satisfactory reusability of the PES/HPC nanofiber membrane was revealed for up to five cycles. According to the mechanism given for the adsorption process, the electrostatic attraction was shown to be the most dominant in increasing the adsorption capacity. Based on these findings, it can be concluded that this unique membrane may be used for wastewater treatment operations with high efficiency and performance.
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http://dx.doi.org/10.3390/membranes12040413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028427PMC
April 2022

Exosomal CD73 from serum of patients with melanoma suppresses lymphocyte functions and is associated with therapy resistance to anti-PD-1 agents.

J Immunother Cancer 2022 03;10(3)

Department of Pharmacy, University of Salerno, Fisciano, Italy

Background: CD73 is an ectonucleotidase producing the immunosuppressor mediator adenosine. Elevated levels of circulating CD73 in patients with cancer have been associated with disease progression and poor response to immunotherapy. Immunosuppressive pathways associated with exosomes can affect T-cell function and the therapeutic efficacy of anti-programmed cell-death protein 1 (anti-PD-1) therapy. Here, we conducted a retrospective pilot study to evaluate levels of exosomal CD73 before and early during treatment with anti-PD-1 agents in patients with melanoma and its potential contribution to affect T-cell functions and to influence the clinical outcomes of anti-PD-1 monotherapy.

Methods: Exosomes were isolated by mini size exclusion chromatography from serum of patients with melanoma (n=41) receiving nivolumab or pembrolizumab monotherapy. Expression of CD73 and programmed death-ligand 1 (PD-L1) were evaluated on exosomes enriched for CD63 by on-bead flow cytometry. The CD73 AMPase activity was evaluated by mass spectrometry, also in the presence of selective inhibitors of CD73. Interferon (IFN)-γ production and granzyme B expression were measured in CD3/28 activated T cells incubated with exosomes in presence of the CD73 substrate AMP. Levels of CD73 and PD-L1 on exosomes were correlated with therapy response. Exosomes isolated from healthy subjects were used as control.

Results: Isolated exosomes carried CD73 on their surface, which is enzymatically active in producing adenosine. Incubation of exosomes with CD3/28 activated T cells in the presence of AMP resulted in a significant reduction of IFN-γ release, which was reversed by the CD73 inhibitor APCP or by the selective A2A adenosine receptor antagonist ZM241385. Expression levels of exosomal CD73 from serum of patients with melanoma were not significantly different from those in healthy subjects. Early on-treatment, expression levels of both CD73 and PD-L1 on exosomes isolated from patients receiving pembrolizumab or nivolumab monotherapy were significantly increased compared with baseline. Early during therapy exosomal PD-L1 increased in responders, while exosomal CD73 resulted significantly increased in non-responders.

Conclusions: CD73 expressed on exosomes from serum of patients with melanoma produces adenosine and contributes to suppress T-cell functions. Early on-treatment, elevated expression levels of exosomal CD73 might affect the response to anti-PD-1 agents in patients with melanoma who failed to respond to therapy.
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http://dx.doi.org/10.1136/jitc-2021-004043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915288PMC
March 2022

Inulin-g-poly-D,L-lactide, a sustainable amphiphilic copolymer for nano-therapeutics.

Drug Deliv Transl Res 2022 Feb 22. Epub 2022 Feb 22.

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

Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy while maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, is a winning choice to ensure a long circulation and colloidal stability, while in some cases, patients could develop PEG-directed immunoglobulins after the first administration. This lead to a phenomenon called accelerated blood clearance (ABC effect), and it is correlated with clinical failure because of the premature removal of the nanosystem from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility, and its GRAS status, the natural polysaccharide inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-g-poly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physicochemical point of view (solubility, 1D and 2D NMR, FT-IR, UV-Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well-known and well-characterized PEGylated counterpart, polyethylene glycol-b-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues.
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http://dx.doi.org/10.1007/s13346-022-01135-4DOI Listing
February 2022

Floating Ricobendazole Delivery Systems: A 3D Printing Method by Co-Extrusion of Sodium Alginate and Calcium Chloride.

Int J Mol Sci 2022 Jan 24;23(3). Epub 2022 Jan 24.

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

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% /, Tween 85 0.1% / and Ricobendazole 5% /; and alginate ink, i.e., a sodium alginate solution at 6% /. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.
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http://dx.doi.org/10.3390/ijms23031280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835811PMC
January 2022

Advanced printable hydrogels from pre-crosslinked alginate as a new tool in semi solid extrusion 3D printing process.

Carbohydr Polym 2022 Jan 20;276:118746. Epub 2021 Oct 20.

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

With the aim to overcome alginate shape fidelity issue during the semisolid extrusion 3D printing and matrix collapsing after drying, we speculated that a pre-crosslinking step of the alginate ink-gel with low amount of Ca could improve the hydrogel performance. To verify this, the influence of pre-crosslinker concentration (10-25 mM) on the ink gel rheological properties were studied and flow behaviour and viscoelastic properties were determined. The developed ink gels were fully characterised by DSC and Magnetic Resonance Imaging (MRI). Moreover, extrudability and the shape retention of extruded forms after printing and after drying were studied. The rheological and MRI data, combined with the morphological analysis of printed forms allowed us to identify the relationship between printability, shape retention and shear thinning behaviour of gels, showing good extrudability for all the pre-crosslinked gels with a calcium concentration between 0.15 and 0.25, corresponding to both egg-box dimers and multimers interactions.
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http://dx.doi.org/10.1016/j.carbpol.2021.118746DOI Listing
January 2022

A Novel Three-Polysaccharide Blend In Situ Gelling Powder for Wound Healing Applications.

Pharmaceutics 2021 Oct 14;13(10). Epub 2021 Oct 14.

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

In this paper, alginate/pectin and alginate/pectin/chitosan blend particles, in the form of an in situ forming hydrogel, intended for wound repair applications, have been successfully developed. Particles have been used to encapsulate doxycycline in order to control the delivery of the drug, enhance its antimicrobial properties, and the ability to inhibit host matrix metalloproteinases. The presence of chitosan in the particles strongly influenced their size, morphology, and fluid uptake properties, as well as drug encapsulation efficiency and release, due to both chemical interactions between the polymers in the blend and interactions with the drug demonstrated by FTIR studies. In vitro antimicrobial studies highlighted an increase in antibacterial activity related to the chitosan amount in the powders. Moreover, in situ gelling powders are able to induce a higher release of IL-8 from the human keratinocytes that could stimulate the wound healing process in difficult-healing. Interestingly, doxycycline-loaded particles are able to increase drug activity against MMPs, with good activity against MMP-9 even at 0.5 μg/mL over 72 h. Such results suggest that such powders rich in chitosan could be a promising dressing for exudating wounds.
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http://dx.doi.org/10.3390/pharmaceutics13101680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541204PMC
October 2021

Bioaerogels: Promising Nanostructured Materials in Fluid Management, Healing and Regeneration of Wounds.

Molecules 2021 Jun 23;26(13). Epub 2021 Jun 23.

Universidade Católica Portuguesa, CBQF-Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal.

Wounds affect one's quality of life and should be managed on a patient-specific approach, based on the particular healing phase and wound condition. During wound healing, exudate is produced as a natural response towards healing. However, excessive production can be detrimental, representing a challenge for wound management. The design and development of new healing devices and therapeutics with improved performance is a constant demand from the healthcare services. Aerogels can combine high porosity and low density with the adequate fluid interaction and drug loading capacity, to establish hemostasis and promote the healing and regeneration of exudative and chronic wounds. Bio-based aerogels, i.e., those produced from natural polymers, are particularly attractive since they encompass their intrinsic chemical properties and the physical features of their nanostructure. In this work, the emerging research on aerogels for wound treatment is reviewed for the first time. The current scenario and the opportunities provided by aerogels in the form of films, membranes and particles are identified to face current unmet demands in fluid managing and wound healing and regeneration.
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http://dx.doi.org/10.3390/molecules26133834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270285PMC
June 2021

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
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