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  1. Article ; Online: Evaluation of Short Chain Fatty Acids (SCFAs) intestinal absorption, following digestion and fermentation of a novel medical device containing partially-hydrolyzed Guar gum plus simethicone

    Federico Benetti / Marta Micheletto / Erik Tedesco / Elisa Gaio / Giorgio Ciprandi

    Journal of Biological Research (2023)

    2023  

    Abstract: Irritable Bowel Syndrome (IBS) is a common disease characterized by alternate symptoms (diarrhea and constipation) and intestinal gas overproduction. A new medical device (Fibergone®), containing Partially Hydrolyzed Guar Gum (PHGG) and Simethicone (SM) ... ...

    Abstract Irritable Bowel Syndrome (IBS) is a common disease characterized by alternate symptoms (diarrhea and constipation) and intestinal gas overproduction. A new medical device (Fibergone®), containing Partially Hydrolyzed Guar Gum (PHGG) and Simethicone (SM) has been proposed for managing patients with bowel disorders. PHGG acts also as a prebiotic so increasing the Short-Chain Fatty Acid (SCFA) production, useful for intestinal physiology. This in vitro study investigated the effects exerted by PHGG+SM on SCFA production and their intestinal absorption following in vitro digestive process and fermentation model. An in vitro model evaluated the digestive process and fermentation using simulated digestive fluids and a human intestinal epithelium in vitro model derived from based on intestinal adenocarcinoma Caco-2 cells (ATCC, HTB-37TM) and organized as a functional monolayer on Transwell® inserts. PHGG+SM was added in experiments and compared with a control (non-treated). SCFA production and absorption were assessed. Viability and barrier integrity of the of the intestinal epithelium model were also evaluated. PHGG+SM significantly (p<0.05) increased SCFAs content after fermentation, indicating that this medical device is effectively fermented at the large intestine level. However, in relation to SCFAs bioavailability, their absorption did not increase compared to the non-treated condition in the light of the physiological contribution of SCFAs resulting from the microflora. PHGG+SM did not affect intestinal epithelium apparent permeability (Papp) and viability. This in vitro study documented that partially hydrolyzed guar gum combined with simethicone significantly affects short-chain fatty acids production and consequently could be fruitfully employed in managing patients with intestinal disorders.
    Keywords irritable bowel syndrome ; short-chain fatty acids ; partially hydrolyzed Guar gum ; simethicone ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher PAGEPress Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Effects of short chain fructo-oligosaccharides on selected skin bacteria

    Cindy Le Bourgot / Claire Meunier / Elisa Gaio / Vincent Murat / Marta Micheletto / Erik Tedesco / Federico Benetti

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 8

    Abstract: Abstract The human skin microbiota plays a key role in the maintenance of healthy skin, ensuring protection and biological barrier by competing with pathogens and by closely communicating with the immune system. The development of approaches which ... ...

    Abstract Abstract The human skin microbiota plays a key role in the maintenance of healthy skin, ensuring protection and biological barrier by competing with pathogens and by closely communicating with the immune system. The development of approaches which preserve or restore the skin microbiota represents a novel target for skincare applications. Prebiotics could be applied to balance almost any microbial community to achieve advantageous effects. However, information about their effectiveness as skin microbiota modulators is limited. The objective of the current study was to evaluate the effects of short chain fructo-oligosaccharides (scFOS) from sugar beet (DP 3–5), well-recognised prebiotics, on some representative bacterial strains of the skin microbiota. We measured the growth and competitive activity of these specific bacteria for the use of scFOS as energy source in minimal medium and in a reconstructed human epithelium (RHE) in vitro model. In minimal growth medium, scFOS promoted and sustained the growth of Staphylococcus epidermidis up to 24 h, considered a beneficial skin commensal bacterium, while inhibiting both Cutibacterium acnes and Staphylococcus aureus growth, regarded as opportunistic pathogens. S. epidermidis showed the highest colonization potential and 1% scFOS was effective in shifting the competition in favour of S. epidermidis with respect to C. acnes in the RHE model. This latter effect was observed following 24 h of exposure, suggesting a long-term effect of scFOS in a highly skin dynamic environment. Therefore, scFOS could be effectively implemented in skincare formulations for recovering skin microbiota homeostasis.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Post-translational modifications in neurodegeneration

    Federico Benetti / Alessandro Didonna

    AIMS Biophysics, Vol 3, Iss 1, Pp 27-

    2015  Volume 49

    Abstract: Post-translational modifications increase proteome functionality for managing all aspects of normal cell biology. They are based on the covalent attachment of functional groups, leading to phosphorylation, acetylation, glycosylation, acylation, ... ...

    Abstract Post-translational modifications increase proteome functionality for managing all aspects of normal cell biology. They are based on the covalent attachment of functional groups, leading to phosphorylation, acetylation, glycosylation, acylation, ubiquitination, SUMOylation and oxidation of protein targets. Post-translational modifications occur at any step of protein life cycle, modulating in time and space protein folding, subcellular localization and activity. Aberrant post-translational modifications of one or more culprit proteins may lead to neurodegeneration, as shown in paradigmatic neurological disorders such as Alzheimer’s, Parkinson’s and prion diseases. In this review, we report the most important post-translational modifications found in neurodegenerative disorders, illustrating the pathophysiological mechanisms in which they are involved. This work highlights the lack of a global framework of post-translational modifications in terms of complexity and regulation. Therefore, in the next future many efforts are required to describe the interplay existing between post-translational modifications and their combinatorial patterns on protein targets.
    Keywords post-translational modifications ; neurodegeneration ; phosphorylation ; acetylation ; glycosylation ; acylation ; ubiquitination ; SUMOylation ; deamidation ; oxidation ; Biology (General) ; QH301-705.5 ; Biotechnology ; TP248.13-248.65
    Subject code 572
    Language English
    Publishing date 2015-12-01T00:00:00Z
    Publisher AIMS Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Comparative Evaluation of Intestinal Absorption and Functional Value of Iron Dietary Supplements and Drug with Different Delivery Systems

    Paolo Pastore / Marco Roverso / Erik Tedesco / Marta Micheletto / Etienne Mantovan / Michela Zanella / Federico Benetti

    Molecules, Vol 25, Iss 5989, p

    2020  Volume 5989

    Abstract: Iron is a fundament micronutrient, whose homeostasis is strictly regulated. Iron deficiency anemia is among the most widespread nutritional deficiencies and its therapy, based on dietary supplement and drugs, may lead to severe side effects. With the aim ...

    Abstract Iron is a fundament micronutrient, whose homeostasis is strictly regulated. Iron deficiency anemia is among the most widespread nutritional deficiencies and its therapy, based on dietary supplement and drugs, may lead to severe side effects. With the aim of improving iron bioavailability while reducing iron oral therapy side effects, novel dietary supplements based on innovative technologies—microencapsulation, liposomes, sucrosomes—have been produced and marketed. In the present work, six iron dietary supplements for different therapeutic targets were compared in terms of bioaccessibility, bioavailability, and safety by using an integrated in vitro approach. For general-purpose iron supplements, ME + VitC (microencapsulated) showed a fast, burst intestinal iron absorption kinetic, which maintained iron bioavailability and ferritin expression constant over time. SS + VitC (sucrosomes), on the other side, showed a slower, time-dependent iron absorption and ferritin expression trend. ME + Folate (microencapsulated) showed a behavior similar to that of ME + VitC, albeit with a lower bioavailability. Among pediatric iron supplements, a time-dependent bioavailability increase was observed for LS (liposome), while PIC (polydextrose-iron complex) bioavailability is severely limited by its poor bioaccessibility. Finally, except for SS + VitC, no adverse effects on intestinal mucosa vitality and barrier integrity were observed. Considering obtained results and the different therapeutic targets, microencapsulation-based formulations are endowed with better performance compared to the other formulations. Furthermore, performances of microencapsulated products were obtained with a lower iron daily dose, limiting the potential onset of side effects.
    Keywords iron ; dietary supplements ; intestinal absorption ; delivery systems ; ferritin ; Organic chemistry ; QD241-441
    Subject code 570
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Detection and Characterization of TiO 2 Nanomaterials in Sludge from Wastewater Treatment Plants of Chihuahua State, Mexico

    Juan Reyes-Herrera / Damaris Acosta-Slane / Hiram Castillo-Michel / Ana E. Pradas del Real / Katarina Vogel-Mikus / Federico Benetti / Marco Roman / Julie Villanova / M. Cecilia Valles-Aragón

    Nanomaterials, Vol 12, Iss 744, p

    2022  Volume 744

    Abstract: TiO 2 nanoparticles (TiO 2 -NPs) have a wide range of industrial applications (paintings, sunscreens, food and cosmetics) and is one of the most intensively used nanomaterials worldwide. Leaching from commercial products TiO 2 -NPs are predicted to ... ...

    Abstract TiO 2 nanoparticles (TiO 2 -NPs) have a wide range of industrial applications (paintings, sunscreens, food and cosmetics) and is one of the most intensively used nanomaterials worldwide. Leaching from commercial products TiO 2 -NPs are predicted to significantly accumulate in wastewater sludges, which are then often used as soil amendment. In this work, sludge samples from four wastewater treatment plants of the Chihuahua State in Mexico were obtained during spring and summer (2017). A comprehensive characterization study was performed by X-ray based (laboratory and synchrotron) techniques and electron microscopy. Ti was detected in all sludge samples (1810–2760 mg/kg) mainly as TiO 2 particles ranging from 40 nm up to hundreds of nm. Micro-XANES data was analyzed by principal component analysis and linear combination fitting enabling the identification of three predominant Ti species: anatase, rutile and ilmenite. Micro-XANES from the smaller Ti particles was predominantly anatase (68% + 32% rutile), suggesting these TiO 2 -NPs originate from paintings and cosmetics. TEM imaging confirmed the presence of nanoscale Ti with smooth surface morphologies resembling engineered TiO 2 -NPs. The size and crystalline phase of TiO 2 -NPs in the sludge from this region suggest increased reactivity and potential toxicity to agro-systems. Further studies should be dedicated to evaluating this.
    Keywords nanoparticles ; sewage sludge ; X-ray microspectroscopy ; synchrotron ; Chemistry ; QD1-999
    Subject code 290
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Lipomatrix

    Andrea Fratter / Vera Mason / Marzia Pellizzato / Stefano Valier / Arrigo Francesco Giuseppe Cicero / Erik Tedesco / Elisa Meneghetti / Federico Benetti

    International Journal of Molecular Sciences, Vol 20, Iss 3, p

    A Novel Ascorbyl Palmitate-Based Lipid Matrix to Enhancing Enteric Absorption of Serenoa Repens Oil

    2019  Volume 669

    Abstract: The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in ... ...

    Abstract The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption. The present work describes and characterizes a new technological matrix (Lipomatrix, Labomar Research, Istrana, TV, Italy) based on a molten fats core in which Ascorbyl Palmitate is embedded, able to deliver lipophilic compounds in a well-dispersed and emulsified form once exposed to duodenal fluids. Authors describe and quantify Lipomatrix delivery of Serenoa repens oil through an innovative in vitro model of human gastro-enteric digestion, reporting results of its improved bioaccessibility, enteric absorption and efficacy compared with not formulated Serenoa repens oil-containing commercial products using in vitro models of human intestine and prostatic tissue.
    Keywords ascorbyl palmitate ; mono and diglycerides of fatty acids ; natural lipophilic compounds ; nutraceutical products ; Serenoa repens oil ; enteric bioaccessibility ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Hydrodynamic chromatography coupled to single-particle ICP-MS for the simultaneous characterization of AgNPs and determination of dissolved Ag in plasma and blood of burn patients

    Roman, Marco / Chiara Rigo / Hiram Castillo-Michel / Ivan Munivrana / Vincenzo Vindigni / Ivan Mičetić / Federico Benetti / Laura Manodori / Warren R. L. Cairns

    Analytical and bioanalytical chemistry. 2016 July, v. 408, no. 19

    2016  

    Abstract: Silver nanoparticles (AgNPs) are increasingly used in medical devices as innovative antibacterial agents, but no data are currently available on their chemical transformations and fate in vivo in the human body, particularly on their potential to reach ... ...

    Abstract Silver nanoparticles (AgNPs) are increasingly used in medical devices as innovative antibacterial agents, but no data are currently available on their chemical transformations and fate in vivo in the human body, particularly on their potential to reach the circulatory system. To study the processes involving AgNPs in human plasma and blood, we developed an analytical method based on hydrodynamic chromatography (HDC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) in single-particle detection mode. An innovative algorithm was implemented to deconvolute the signals of dissolved Ag and AgNPs and to extrapolate a multiparametric characterization of the particles in the same chromatogram. From a single injection, the method provides the concentration of dissolved Ag and the distribution of AgNPs in terms of hydrodynamic diameter, mass-derived diameter, number and mass concentration. This analytical approach is robust and suitable to study quantitatively the dynamics and kinetics of AgNPs in complex biological fluids, including processes such as agglomeration, dissolution and formation of protein coronas. The method was applied to study the transformations of AgNP standards and an AgNP-coated dressing in human plasma, supported by micro X-ray fluorescence (μXRF) and micro X-ray absorption near-edge spectroscopy (μXANES) speciation analysis and imaging, and to investigate, for the first time, the possible presence of AgNPs in the blood of three burn patients treated with the same dressing. Together with our previous studies, the results strongly support the hypothesis that the systemic mobilization of the metal after topical administration of AgNPs is driven by their dissolution in situ. Graphical Abstract Simplified scheme of the combined analytical approach adopted for studying the chemical dynamics of AgNPs in human plasma/blood
    Keywords X-radiation ; absorption ; algorithms ; antibiotics ; atomic absorption spectrometry ; blood plasma ; chromatography ; fluorescence ; humans ; hydrodynamics ; image analysis ; medical equipment ; nanosilver ; patients
    Language English
    Dates of publication 2016-07
    Size p. 5109-5124.
    Publishing place Springer Berlin Heidelberg
    Document type Article
    ISSN 1618-2642
    DOI 10.1007/s00216-015-9014-6
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: Protamine nanocapsules as carriers for oral peptide delivery

    Thwala, Lungile Nomcebo / Diego Pan Delgado / Kevin Leone / Ilaria Marigo / Federico Benetti / Miguel Chenlo / Clara V. Alvarez / Sulay Tovar / Carlos Dieguez / Noemi Stefania Csaba / Maria Jose Alonso

    Journal of controlled release. 2018 Dec. 10, v. 291

    2018  

    Abstract: Peptides represent a promising therapeutic class with the potential to alleviate many severe diseases. A key limitation of these active molecules relies on the difficulties for their efficient oral administration. The objective of this work has been the ... ...

    Abstract Peptides represent a promising therapeutic class with the potential to alleviate many severe diseases. A key limitation of these active molecules relies on the difficulties for their efficient oral administration. The objective of this work has been the rational design of polymer nanocapsules (NCs) intended for the oral delivery of peptide drugs. For this purpose, we selected insulin glulisine as a model peptide. The polymer shell of the NCs was made of a single layer of protamine, a cationic polypeptide selected for its cell penetration properties, or a double protamine/polysialic acid (PSA) layer. Insulin glulisine-loaded protamine and protamine/PSA NCs, prepared by the solvent displacement method, exhibited a size that varied in the range of 200–400 nm and a neutral surface charge (from +8 mV to −6 mV), depending on the formulation. The stability of the encapsulated peptide was assessed using circular dichroism and an in vitro cell activity study. Colloidal stability studies were also performed in simulated intestinal media containing enzymes and the results indicated that protamine NCs were stable and able to protect insulin from the harsh intestinal environment, and that this capacity could be further enhanced with a double PSA-Protamine layer. These NCs were freeze-dried and stored at room temperature without alteration of the physicochemical properties. When the insulin-loaded protamine NCs were administered intra-intestinally to diabetic rats (12 h fasting) it resulted in a prolonged glucose reduction (60%) as compared to the control insulin solution. This work raises prospects that protamine NCs may have a potential as oral peptide delivery nanocarriers.
    Keywords ambient temperature ; animal disease models ; circular dichroism spectroscopy ; diabetes ; disease severity ; drugs ; encapsulation ; enzymes ; fasting ; freeze drying ; glucose ; insulin ; intestines ; nanocapsules ; nanocarriers ; oral administration ; physicochemical properties ; polymers ; polypeptides ; rats ; solvents ; storage temperature
    Language English
    Dates of publication 2018-1210
    Size p. 157-168.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2018.10.022
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    Zs.A 2055: Show issues Location:
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  9. Article ; Online: Prion protein accumulation in lipid rafts of mouse aging brain.

    Federica Agostini / Carlos G Dotti / Azucena Pérez-Cañamás / Maria Dolores Ledesma / Federico Benetti / Giuseppe Legname

    PLoS ONE, Vol 8, Iss 9, p e

    2013  Volume 74244

    Abstract: The cellular form of the prion protein (PrP(C)) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be ...

    Abstract The cellular form of the prion protein (PrP(C)) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrP(C). In old mice, this change favors PrP(C) accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrP(C) translocation into detergent-resistant membranes (DRMs), we looked at PrP(C) compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO) mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrP(C) in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases.
    Keywords Medicine ; R ; Science ; Q
    Subject code 630
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers

    Niu, Zhigao / Aloïse Mabondzo / Carlos Diéguez / David Gonzalez-Touceda / Erik Tedesco / Federico Benetti / Ilaria Marigo / Isabella Monia Montagner / Manuel J. Santander-Ortega / María J. Alonso / Sulay Tovar

    Journal of Controlled Release. 2017,

    2017  

    Abstract: The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected ... ...

    Abstract The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80. This selected NCs composition, produced by the solvent displacement technique, exhibited the following key features: (i) an average size of 180nm and a low polydispersity (0.1), (ii) a high insulin association efficacy (80–90% AE), (iii) a good colloidal stability upon incubation in simulated intestinal fluids (SIF, FaSSIF-V2, FeSSIF-V2), and (iv) the capacity to control the release of the associated insulin for >4h. Furthermore, using the Caco-2 model cell line, PARG nanocapsules were able to interact with the enterocytes, and reversibly modify the TEER of the monolayer. Both cell adhesion and membrane permeabilization could account for the pronounced transport of the NCs-associated insulin (3.54%). This improved interaction was also visualized by confocal fluorescent microscopy following oral administration of PARG nanocapsulesto mice. Finally, in vivo efficacy studies performed in normoglycemic rats showed a significant decrease in their plasma glucose levels after treatment. In conclusion, here we disclose key formulation elements for making possible the oral administration of peptides.
    Keywords arginine ; blood glucose ; cell adhesion ; deoxycholic acid ; enterocytes ; fluorescence microscopy ; insulin ; mice ; models ; nanocapsules ; oils ; oleic acid ; oral administration ; peptides ; rats ; screening ; solvents ; surfactants
    Language English
    Size p. .
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2017.02.024
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