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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 involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (PLGA micro-particles), containing a model antibacterial drug (vancomycin hydrochloride). In order to understand the key parameters ruling the performance of this delivery system, we developed a mathematical model able to discriminate the drug diffusion inside micro-particles and within the gel phase, eventually providing to predict the drug release kinetics. The model reliability was confirmed by fitting to experimental data, proposing as a powerful theoretical approach to design and optimize such in situ delivery systems.

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 Quantitative Systems Pharmacology, an emerging discipline aimed at the application of systems biology modeling to drug discovery. In the wide frame of Biological Engineering, this chapter deals with drug delivery systems based on polymeric matrices as they are very versatile and reliable. In particular, attention is focused on the description of polymeric matrices and their characterization by means of different experimental techniques such as rheology, low-field NMR, crioporosimetry, small-angle neutron scattering, release, and swelling tests. Then, the release mechanisms are presented and discussed and, finally, a mathematical model explaining matrix viscoelasticity is described in detail.

Bacterial infections represent an important problem in the orthopaedic field as they can develop either immediately after the surgical intervention or after some years [1]. In particular, they can be very problematic in the case of implants as, often, their elimination requires the surgical removal of the infected implant. Accordingly, a possible solution strategy is to act locally by coating the implant by an antibacterial system that has to be easily applicable, biocompatible (it must not hinder implant osseointegration) and able to provide the desired release kinetics of the selected antibacterial drug. In this frame, this paper focuses the attention on a biphasic polymeric system made up by a thermos-reversible hydrogel, constituted by Poloxamer 407, hosting a dispersed phase represented by polylactic-co-glycolic acid 50:50 (PLGA) micro-particles containing the antibacterial drug (vancomycin hydrochloride). While below room temperature, the Poloxamer 407/water system behaves as a solution and it is easily spreadable on the implant surface, upon temperature rise to the physiological value, the Poloxamer 407/water solution undergoes gelation. Basically, gelation ensures that the PLGA micro-particles remain in situ, between the implant surface and the growing bone. On the contrary, the controlled drug delivery is due to vancomycin hydrochloride release from PLGA micro-particles, acting as the reservoir phase. The primary aim of this paper is to develop a mathematical model able to properly describe the in vitro vancomycin hydrochloride release from the biphasic system.

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 hydrogel. By relying on the independent determination of all its parameters, the model proved to predict the ascorbic acid transport inside the agar hydrogel properly. Thus, it may be considered a powerful theoretical tool for the design of polymeric films (packaging) aimed at releasing antioxidant agents inside food. Fil: Chiarappa, Gianlucca. Università degli Studi di Trieste; Italia Fil: De'nobili, Maria Dolores. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias. Instituto de Tecnología de Alimentos y Procesos Quimicos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Tecnología de Alimentos y Procesos Quimicos.; Argentina Fil: Rojas, Ana Maria Luisa. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Industrias. Instituto de Tecnología de Alimentos y Procesos Quimicos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Tecnología de Alimentos y Procesos Quimicos.; Argentina Fil: Abrami, Michela. Università degli Studi di Trieste; Italia Fil: Lapasin, Romano. Università degli Studi di Trieste; Italia Fil: Grassi, Federico Guillermo. Università degli Studi di Trieste; Italia Fil: Ferreira, Jose. University Of Coimbra. Centre For Mathematics; Portugal Fil: Gudiño, Elias. Universidade Federal do Paraná; Brasil Fil: de Oliveira, Paula. University Of Coimbra. Centre For Mathematics; Portugal Fil: Grassi, Mario. Università degli Studi di Trieste; Italia

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 6th IAPC Symposium held in Zagreb (HR) on September 2017. Particular attention is devoted to the determination of the mesh size distribution of gels polymeric network and the determination of the pore size distribution of microporous systems such as scaffolds, bones, and porous gels. In addition, we report on a very recent application of LF-NMR for monitoring lung functioning in patients suffering from chronic pulmonary diseases like cystic fibrosis. The main findings of this work consist in providing a very simple and accurate approximation of a general theory devoted to evaluating the relation existing among four fundamental polymeric network parameters, i.e. the polymer volume fraction inside the hydrogel, mesh size, hydraulic radius, and the radius of the cylinder ideally embedding each polymeric network chain. Furthermore, we demonstrated the potentiality of LF-NMR in the characterization of different polymeric systems among which the sputum of patients suffering from chronic pulmonary diseases appears the most innovative application for its simplicity, rapidity, effectiveness, and potential impact in the everyday clinic.

A typical example of viscoelastic matrices is represented by polymeric particles devoted to the controlled release of active agents (drugs) that swell when put in contact with an external solvent, typically a physiological medium. Although, in general, physiological fluids can be considered Newtonian, this is not always the case, let us consider, for example, the mucus present in different organs such lungs when affected by chronic obstructive disease (bacterial infections and cystic fibrosis, for instance). Swelling allows the release of the embedded drug due to the enlargement of the meshes of the polymeric network. The demand for more and more sophisticated drug delivery systems requires to theoretically study in high detail the mass transport phenomena involved in the swelling and release processes. The present study concerns with the mathematical modelling of both transport processes in the case of a viscoelastic matrix swollen by a viscoelastic fluid. While matrix viscoelasticity is accounted for by the generalized Maxwell model, a mean relaxation time accounts for fluid viscoelasticity. The model assumes that solvent uptake gives origin to an internal stress, due the polymeric network reaction to enlargement, able to affect solvent transport and thus, drug release. Despite the complexity connected to the theoretical description of stress and deformation in the swelling matrix, it is generally assumed that the stress state can be approximated by a scalar that can be viewed as an osmotically induced viscoelastic swelling pressure related to the trace of the stress tensor. At the same time, assuming incompressible materials and vanishing deformation gradient inside the matrix, deformation can be simply represented by a scalar quantity (the radial deformation in the case of spheres). Model simulations indicate that the higher the swelling solvent relaxation time, the lower the effect of matrix viscoelastic properties on mass transport phenomena

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 cellulose sources/features and cellulose chemical modifications employed to improve its properties. We then move to the description of cellulose potential applications in biomedicine. In this field, cellulose is most considered in recent research in the form of nano-sized particle, i.e., nanofiber cellulose (NFC) or cellulose nanocrystal (CNC). NFC is obtained from cellulose via chemical and mechanical methods. CNC can be obtained from macroscopic or microscopic forms of cellulose following strong acid hydrolysis. NFC and CNC are used for several reasons including the mechanical properties, the extended surface area and the low toxicity. Here we present some potential applications of nano-sized cellulose in the fields of wound healing, bone-cartilage regeneration, dental application and different human diseases including cancer. To witness the close proximity of nano-sized cellulose to the practical biomedical use, examples of recent clinical trials are also reported. Altogether, the described examples strongly support the enormous application potential of nano-sized cellulose in the biomedical field.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. This paper focuses on a thermodynamic model built to predict the reduction of organic drug melting temperature and enthalpy with nanocrystal size decrease. Indeed, this valuable information enables us to evaluate the increase of drug solubility, an aspect of paramount importance for poorly water-soluble organic drugs since a solubility increase is reflected in a bioavailability enhancement. In particular, the model considers the effect of nanocrystals shape (spherical, cylindrical, and parallelepiped-shaped) and morphology (from platelet to needle nanocrystals) on the melting temperature and enthalpy reduction with crystal size decrease. Nimesulide, a typical nonsteroidal and poorly water-soluble drug with anti-inflammatory action, has been chosen as a model drug to test model reliability. Model outcomes suggest that the reduction of melting temperature and enthalpy mainly depends on the ratio between crystals surface area and volume, i.e., on the ratio between the number of surface and bulk molecules constituting the nanocrystal network. The obtained prediction of solubility enhancement and the successful comparison with the outcomes obtained from a molecular dynamics approach, in terms of melting temperature and enthalpy decrease, have confirmed the reliability of the proposed model.

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 is urgently required. small-interfering rna (sirna) molecules are short, double-stranded rnas that specifically recognize and bind the mrna of a target gene to inhibit gene expression. despite the great therapeutic potential of sirnas towards many human tumors including hcc, their use is limited by suboptimal delivery. Areas covered: In this review, we outline the current data regarding the therapeutic potential of siRNAs in HCC and describe the development of effective siRNA delivery systems. We detail the key problems associated with siRNA delivery and discuss the possible solutions. Finally, we provide examples of the various siRNA delivery strategies that have been employed in animal models of HCC and in human patients enrolled in clinical trials. Expert opinion: Despite the existing difficulties in siRNA delivery for HCC, the increasing scientific attention and breakthrough studies in this field is facilitating the design of novel and efficient technical solutions that may soon find practical applications

Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.

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 physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.

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 tools enabling a rational approach adapting to each patient, NABDs delivery brings to our attention new aspects of drug delivery due to the NABDs fragile nature and way of action. This review aims to present and discuss the mathematical modelling of drug release from natural polysaccharides matrices with particular care to the description of the chemical and physical phenomena ruling drug delivery.