Mario Grassi

Mario Grassi
University of Trieste | UNITS · Department of Engineering and Architecture

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234
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Publications (234)
Chapter
It is probably not well known that 4000 years BC. Sumerians were able to prepare many medicaments and illness was considered a sort of divine punishment while healing was the consequent purification, a viewpoint that has heavily affected the Western world up to the modern age. The scientific darkness permeating Europe after the end of the Roman Emp...
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Since the 1980s, drug activation by grinding or co-grinding has evolved considerably, allowing the conversion of microcrystals into nanocrystals or amorphous phases, whose increased solubility brings a significant improvement in drug bioavailability. This has prompted many researchers to investigate and understand the entire grinding/co-grinding pr...
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The correlation between in vivo and in vitro data is yet not sufficiently optimized to allow a significant reduction and replacement of animal testing in pharmaceutical development. One of the main reasons for this lies in the poor mechanistic understanding and interpretation of the physical mechanisms enabling formulation rely on for deploying the...
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The prediction of drug dissolution profiles is crucial for elucidating the pharmacokinetic behaviour of drugs and the bioavailability of dosage forms. In this work, we develop a mathematical model to describe the dissolution process of irregularly shaped particles. We use a complete dissolution model that accounts for both surface kinetics and conv...
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We present a statistical mechanics theory of rubber-like elasticity in swollen and unswollen polymer networks characterized by explicitly non-Gaussian distribution functions (Laplace’s, Cauchy’s, and continuous Poisson’s in the exponential limit). An important outcome is the derivation of new families of statistical and mechanical laws, including a...
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Scleroglucan (Sclg) and Guar Gum (GG) are both capable to give gels in the presence of borax and this study is focused on how a mixed system of the two polysaccharides can be affected by the addition of borax. The anisotropic swelling behavior of tablets obtained by compression of the freeze-dried new gel system is also investigated and compared to...
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The treatment of urological cancers has been significantly improved in recent years. However, for the advanced stages of these cancers and/or for those developing resistance, novel therapeutic options need to be developed. Among the innovative strategies, the use of small interfering RNA (siRNA) seems to be of great therapeutic interest. siRNAs are...
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Background: For hepatocellular carcinoma (HCC), effective therapeutic approaches are lacking. As aberrant gene methylation is a major contributor to HCC development, demethylating drugs such as 5-azacytidine (5-Aza) have been proposed. As most 5-Aza mechanisms of action are unknown, we investigated its phenotypic/molecular effects. Methods: 5-Az...
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Cystic fibrosis (CF) is a disease characterized by the production of viscous mucoid secretions in multiple organs, particularly the airways. The pathological increase of proteins, mucin and biological polymers determines their arrangement into a three-dimensional polymeric network, affecting the whole mucus and impairing the muco-ciliary clearance...
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In the last decades, Green Chemistry has been gaining widespread attention within the pharmaceutical field. It is thus very important to bring more sustainable approaches into the design and manufacture of effective oral drug delivery systems. This review focuses on spray congealing and mechanochemical activation, two technologies endorsing differe...
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A simple relation between pendant groups of polymers in hydrogels is introduced to determine the crosslink density of (complex) hydrogel systems (mixtures of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) modified nanocellulose, alginate, scleroglucan and Laponite in addition of crosslinking agents). Furthermore, the rheological properties and their...
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The open border between non-living and living matter, suggested by increasingly emerging fields of nanoscience interfaced to biological systems, requires a detailed knowledge of nanomaterials properties. An account of the wide spectrum of phenomena, belonging to physical chemistry of interfaces, materials science, solid state physics at the nanosca...
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The study of bone morphology is of great importance as bone morphology is influenced by factors such as age and underlying comorbidities and is associated with bone mechanical properties and fracture risk. Standard diagnostic techniques used in bone disease, such as Dual-Energy X-ray absorptiometry and ultrasonography do not provide qualitative and...
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Background As most cystic fibrosis (CF) patients progress to respiratory failure, lung functionality assessment is pivotal. We previously developed a test that indirectly monitors airways (inflammation/functional test) by measuring the spin-spin relaxation time (T2m) of the water hydrogens present in CF sputum. Here the T2m significance in the moni...
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Hepatocellular carcinoma (HCC) is the sixth most common type of tumor and the second leading cause of tumor-related death worldwide. Liver cirrhosis is the most important predisposing factor for HCC. Available therapeutic approaches are not very effective, especially for advanced HCC, which is the most common form of the disease at diagnosis. New t...
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Following the implantation of indwelling medical devices, bacteria inoculated during the surgery or coming from a preexistent focus of infection race for the medical surface where they attach. Adaptation to survive is a common feature of life, and microorganisms are not an exception. Bacteria form, in short periods of time, a habitat-the biofilm-wh...
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This work reports on a novel method to synthesize hydrophobically-modified hydrogels by curing epoxy monomers with amines. The resulting networks contain hydrophilic poly(ethylene glycol) (PEG) segments, poly(propylene glycol) (PPG) segments, and C18 alkyl segments. By varying the content of C18 segments, networks with different hydrophilic-lipophi...
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The influence of the physical, rheological, and process parameters on the cellulose nanocrystal (CNC) drops before and after external gelation in a CaCl2 solution was investigated. The dominant role of the CNC’s colloidal suspension properties, such as the viscous force, inertial, and surface tension forces in the fluid dynamics was quantitatively...
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Hydrogels' viscoelastic behavior is crucial in several applications and an in‐depth knowledge and characterization of this property is essential to select the most appropriate gel for the specific use. Oscillatory shear measurements are the most commonly used techniques to perform the viscoelastic characterization of hydrogels, among other material...
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The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds. In this work, a thermo- and pH-responsive hydrogel (P-CHP407) was prepared from an ad hoc synthesized amphiphi...
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Due to its hydroxyl terminal groups, Poloxamer ® 407 (P407), a commercially available poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer can be used as macrodiol for the synthesis of high molecular weight amphiphilic poly(ether urethane)s (PEUs). This work was aimed at studying the effect of P407 purifi...
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Given the lack of effective treatments for Hepatocellular carcinoma (HCC), the development of novel therapeutic approaches is very urgent. Here, siRNAs were delivered to HCC cells by a synthetic polymer containing α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide-(PHEA) derivatized with diethylene triamine (DETA) and bearing in the side chain galactose (...
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Catanionic vesicles are emerging interesting structures for bioapplications. They self-generate by a pairing of oppositely charged ionic surfactants that assemble into hollow structures. Specifically, the anionic-cationic surfactant pair assumes a double-tailed zwitterionic behavior. In this work, the multilamellar-to-unilamellar thermal transition...
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p class="ADMETabstracttext">The aim of this theoretical paper is to develop a mathematical model for describing the dissolution process, in a finite liquid environment, of an ensemble of poly-dispersed drug particles, in form of sphere, cylinder and parallelepiped that can undergo solubility reduction due to phase transition induced by dissolution....
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Background Ovary carcinoma (OC) is the most lethal gynecological neoplasm due to the late diagnoses and to the common development of resistance to platinum-based chemotherapy. Thus, novel therapeutic approaches are urgently required. In this regard, the strategy of drug repurposing is becoming attractive. By this approach, the effectiveness of a dr...
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The combination of Low-Field NMR relaxometry (LF-NMR) and rheological analyses was used to investigate the kinetics of aging and structural evolution of salt-free aqueous Laponite dispersions with concentrations ranging from 0.33 to 2.00 wt%. The examination of LF-NMR results reveals that the rate of nanoclay delamination increases with increasing...
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Purpose: To develop a novel approach to monitor lung ventilation/inflammation in cystic fibrosis (CF) patients. Lung assessment in CF patients is relevant given that most patients succumb to respiratory failure. Respiratory functional tests (forced expiratory volume in the first second; FEV1 ) and inflammatory markers are used to test pulmonary ve...
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The unmet need for novel therapeutic options for ovarian cancer (OC) deserves further investigation. Among the different novel drugs, small interfering RNAs (siRNAs) are particularly attractive because of their specificity of action and efficacy, as documented in many experimental setups. However, the fragility of these molecules in the biological...
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To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but the...
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Cellulose is a natural homopolymer, composed of β-1,4- anhydro-d-glucopyranose units. Unlike plant cellulose, bacterial cellulose (BC), obtained from species belonging to the genera of Acetobacter, Rhizobium, Agrobacterium, and Sarcina through various cultivation methods and techniques, is produced in its pure form. BC is produced in the form of ge...
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Background: The new concepts of personalized and precision medicine require the design of more and more refined delivery systems. In this frame, hydrogels can play a very important role as they represent the best surrogate of soft living tissues for what concerns rheological properties. Thus, this paper focusses on a global theoretical approach ab...
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This work deals with the effect of temperature on the thermal-gelation process of water solutions containing chitosan β-glycerolphosphate disodium salt hydrate. In particular, the attention is focused on the role played by temperature on the gel final properties, a very important aspect in the frame of drug delivery systems. The study was performed...
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Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could in...
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Peptidyl‐prolyl cis–trans isomerase, NIMA‐interacting 1 (PIN1) is a peptidyl‐prolyl isomerase that binds phospho‐Ser/Thr‐Pro motifs in proteins and catalyzes the cis–trans isomerization of proline peptide bonds. PIN1 is overexpressed in several cancers including high‐grade serous ovarian cancer. Since few therapies are effective against this cancer...
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Nature makes pervasive use of homochirality (e.g., d-sugars and l-peptides) to assemble biomolecules, whose interactions determine life processes. d-amino acids rarely occur, and their effects are not yet completely understood. For a long time, structural complexity (e.g., polypeptides and constrained molecules) was considered a requirement for ach...
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Purpose: This paper is based on the characterization of the rheological and Low Field NMR (LF-NMR) properties of an interpenetrated hydrogel made up by poly(N-vinyl-2-pyrrolidone) and sodium alginate. The final aim is to use the hydrogel as a delivery matrix for liposomes, widely used tools in the drug delivery field. Methods: Rheology, LF-NMR,...
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The limited stability of catanionic vesicles has discouraged their wide use for encapsulation and controlled release of active substances. Their structure can easily break down to form lamellar phases, micelles or rearrange into multilamellar vesicles, as a consequence of small changes in their composition. However, despite the limited stability, c...
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Short peptide hydrogels are attractive biomaterials but typically suffer from limited mechanical properties. Inclusion of other nanomaterials can serve the dual purpose of hydrogel reinforcement and of conferring additional physico-chemical properties ( e.g., self-healing, conductivity), as long as they do not hamper peptide self-assembly. In parti...
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This paper focusses on the mathematical modeling of the ascorbic acid (antioxidant) release from a pectin edible film (packaging) to an agar hydrogel (food). The proposed model considers the viscoelastic properties of the polymeric film, the solid ascorbic acid dissolution inside the film, its degradation and diffusion in both the film and the hydr...
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Despite the advances in anticancer therapies, their effectiveness for many human tumors is still far from being optimal. Significant improvements in treatment efficacy can come from the enhancement of drug specificity. This goal may be achieved by combining the use of therapeutic molecules with tumor specific effects and delivery carriers with tumo...
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The focus of this paper is on the theoretical interpretation of Low Field Nuclear Magnetic Resonance (LF-NMR) data regarding hydrogels architecture and on the most interesting applications of LF-NMR presented by this research group at the 6<sup>th</sup> IAPC Symposium held in Zagreb (HR) on September 2017. Particular attention is devoted to the det...
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In situ forming ophthalmic gels need to be fine-tuned considering all the biopharmaceutical challenges of the front of the eye in order to increase drug residence time at the application site resulting in its improved bioavailability and efficacy. The aim of this study was to develop in situ forming ophthalmic poloxamer P407/ poloxamer P188/chitosa...
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We consider a polymeric spherical platform containing a solid dispersed drug that is in contact with a solvent fluid. While swelling, a non-Fickian sorption of the solvent molecules occurs induced by the effect of the viscoelastic properties of the polymer. The solid drug in contact with the solvent fluid dissolves and a Fickian release of dissolve...
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Since its origins, Chemical Engineering has undergone huge transformations and most importantly led to the birth of Biological Engineering, a Chemical Engineering branch devoted to studying the biomedical problems by means of the mass, energy, and momentum balances. Thus, Biological Engineering can represent the Chemical Engineering contribution to...
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Because of its high biocompatibility, bio-degradability, low-cost and easy availability, cellulose finds application in disparate areas of research. Here we focus our attention on the most recent and attractive potential applications of cellulose in the biomedical field. We first describe the chemical/structural composition of cellulose fibers, the...
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Purpose: Development of a reliable, simple method to monitor lung condition in cystic fibrosis (CF) patients. Lung functionality assessment in CF patients is relevant, as most of them still die of respiratory failure. In lung mucus (sputum) of CF patients, components such as proteins, biopolymers, DNA, bacteria, and mucin are pathologically increa...
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This paper focusses on a thermodynamic model built to predict the reduction of organic drugs melting temperature and enthalpy with nano-crystals size decrease. Indeed, this valuable information enables us to evaluate the increase of drug solubility, aspect of paramount importance for poorly water-soluble organic drugs since a solubility increase is...
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The new concept of personalized medicine and the affirmation of Nucleic Acid Based Drugs (NABDs), an emerging class of bio-drugs constituted by short sequences of either DNA or RNA, represent a new challenge for the mathematical modelling in the drug delivery and adsorption field. Indeed, whether patient uniqueness asks for the use of theoretical t...
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Sol-gel transition of carboxylated cellulose nanocrystals is investigated using rheology, SAXS, NMR and optical spectroscopies to unveil the distinctive roles of ultrasounds treatment and ions addition. Besides cellulose fibers fragmentation, sonication treatment induces fast gelling of the solution. Gelation is induced independently on the additio...
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Over the past ten years, the global biopharmaceutical market has remarkably grown, with ten over the top twenty worldwide high performance medical treatment sales being biologics. Thus, biotech R&D (research and development) sector is becoming a key leading branch, with expanding revenues. Biotechnology offers considerable advantages compared to tr...
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Viscosupplementation is a therapeutic approach for osteoarthritis treatment, where the synovial fluid, the natural lubricant of the joints, is replaced by viscoelastic solutions with rheological properties comparable or better than the starting material. This study presents the development of an innovative platform for viscosupplementation, based o...
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The effects that an increase of environmental pH has on the triple helix of scleroglucan (Sclg) and on the Sclg/borax hydrogel are reported. Rheological experiments show that the hydrogel is less sensitive to pH increase than Sclg alone, while at pH = 14 a dramatic viscosity decrease takes place for both systems. This effect is evidenced also by th...
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Both Laponite and scleroglucan can find several applications in various fields (from industrial to biomed-ical one) in virtue of their peculiar features and rheological properties displayed in aqueous phases. Structural states of Laponite dispersions strongly depend on concentration and ionic strength. When attractive and repulsive interparticle in...
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Introduction: hepatocellular carcinoma (hcc) is the predominant form of primary liver cancer and the second leading cause of cancer-associated mortality worldwide. available therapies for hcc have limited efficacy due to often late diagnosis and the general resistance of hcc to anti-cancer agents; therefore, the development of novel therapeutics i...
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Eukaryotic elongation factor 1A (eEF1A), a protein involved in protein synthesis, has two major isoforms, eEF1A1 and eEF1A2. Despite the evidences of their involvement in hepatocellular carcinoma (HCC), the quantitative contribution of each of the two isoforms to the disease is unknown. We depleted the two isoforms by means of siRNAs and studied th...
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siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiologica...
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The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethyle...