Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure-property relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.
In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs.
This tutorial review describes the state of current research and findings on the phenomena of polymer crystallisation under processing conditions, with particular emphasis on the effects of fluid flow. Preliminarily, it is stated why the crystallisation processes are relevant in polymer science, then the motivation of the study is briefly outlined. The remaining of the paper is divided in two parts. In the first part of the review, the basics of polymer crystallisation are summarized; the main factors acting on the process are identified; and the methods to investigate and to quantify the crystallization are described. A brief summary of the modelling approaches is also proposed. In the second part of the review, a similar path was followed in order to analyse the complex framework of phenomena collectively known as flow induced crystallisation. Therefore, the experimental techniques used are listed and the main findings are reported. A reference to the modelling approaches proposed in the literature is also summarized. Throughout the review, a selection of the literature in the field is of course cited.
In this work the behavior of hydrogel-based matrices, the most widespread systems for oral controlled release of pharmaceuticals, has been mathematically described. In addition, the calculations of the model have been validated against a rich set of experimental data obtained working with tablets made of hydroxypropyl methylcellulose (a hydrogel) and theophylline (a model drug). The model takes into account water uptake, hydrogel swelling, drug release, and polymer erosion. The model was obtained as an improvement of a previous code, describing the diffusion in concentrated systems, and obtaining the erosion front (which is a moving boundary) from the polymer mass balance (in this way, the number of fitting parameters was also reduced by one). The proposed model was found able to describe all the observed phenomena, and then it can be considered a tool with predictive capabilities, useful in design and testing of new dosage systems based on hydrogels.
The crystallization of a polymer melt, taking place during transformation processes, has a great impact on the process itself, mainly because it causes a large increase in the viscosity (hardening). Knowledge of the hardening kinetics is important for modeling and controlling the transformation processes. In this work, first an overview is given of the experimental and modeling work on the hardening of crystallizing polymers. Next, we present isothermal crystallization experiments using differential scanning calorimetry (DSC) and rotational rheometry to measure the dynamic viscosity. The evolution of the relative crystallinity and normalized complex viscosity are correlated by a novel technique which allows simultaneous analysis of several runs, even if they are not carried out at same temperatures; the main requirement with the traditional technique. The technique, described in detail in this paper, provides an experimental relationship between the crystallinity and the hardening, i. e. the increase in the viscosity. Moreover, by measuring the dynamic viscosity at different frequencies, surprisingly, a master curve is obtained which combines the effects of shear rate, temperature and the level of crystallinity.
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