Effect of pH on the viscoelastic properties of pig gastric mucus.

Mucus is a biomaterial with peculiar, gel-like viscoelastic properties, and bearing different functionalities, depending on the different mucosae it covers. It is clear that these functionalities have to stay effective throughout the in vivo broad range of physiological pH values at which the mucus is exposed. We sought here to determine the effect of pH on the rheological properties of ex vivo mucus. We demonstrate that viscoelastic properties of gastric mucus are quite "stable" to pH changes, in marked contrast with the pH sensitivity of purified mucin gels. We also find that the rheological features of porcine gastric mucus are reversible when the system is first alkalized up to solubilization (pH > 8.5) and then re-acidified to its initial pH value.

Investigation on the thermal gelation of Chitosan/ß-Glycerophosphate solutions.

This work deals with the effect of temperature on the thermal-gelation process of water solutions containing chitosan ß-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 by combining rheology and low field nuclear magnetic resonance, two approaches that revealed to be highly synergic as they can detect different aspects of the developing polymeric network. This study indicates that 30 °C represent a sort of threshold for both the gelation kinetics and the gel final properties. Indeed, above this temperature, gelation kinetics was rapid and yielded to a strong gel. On the contrary, a slow kinetics and a final weak gel occurred below 30 °C. Finally, rheology and low field NMR allowed, independently, evaluating the time evolution of the network mesh size upon gelation.

Growth and in vivo stresses traced through tumor mechanics enriched with predator-prey cells dynamics.

Mechanical stress accumulating during growth in solid tumors plays a crucial role in the tumor mechanobiology. Stresses arise as a consequence of the spatially inhomogeneous tissue growth due to the different activity of healthy and cancer cells inhabiting the various districts of the tissue, an additional piling up effect, induced by stress transferring across the scales, contributing to determine the total stress occurring at the macroscopic level. The spatially inhomogeneous growth rates accompany nonuniform and time-propagating stress profiles, which constitute mechanical barriers to nutrient transport and influence the intratumoral interstitial flow, in this way deciding the starved/feeded regions, with direct aftereffects on necrosis, angiogenesis, cancer aggressiveness and overall tumor mass size. Despite their ascertained role in tumor mechanobiology, stresses cannot be directly appraised neither from overall tumor size nor through standard non-invasive measurements. To date, the sole way for qualitatively revealing their presence within solid tumors is ex vivo, by engraving the excised masses and then observing opening between the cut edges. Therefore, to contribute to unveil stresses and their implications in tumors, it is first proposed a multiscale model where Volterra-Lotka (predator/prey-like) equations describing the interspecific (environment-mediated) competitions among healthy and cancer cells are coupled with equations of nonlinear poroelasticity. Then, an experimental study on mice injected subcutaneously with a suspension of two different cancer cell lines (MiaPaCa-2 and MDA.MB231) was conducted to provide experimental evidences that gave qualitative and some new quantitative confirmations of the theoretical model predictions.

Modulation of drug release from hydrogels by using cyclodextrins: the case of nicardipine/beta-cyclodextrin system in crosslinked polyethylenglycol.

A simple approach is presented to modulate drug delivery from swellable systems by using complexants. The effect of complexants has been interpreted by means of simple mass balances on diffusing species and the involved relevant parameters have been individuated. The application of this strategy to the release of nicardipine (NIC) from swellable systems by using beta-cyclodextrin (CD) as complexant has evidenced the potential of the approach to tailor drug release. Crosslinked polyethyleneglycol has been synthesized, characterized and used as the swellable matrix. Swelling kinetics, NIC and CD diffusivities in the swollen matrix and NIC/CD phase solubility studies have been performed. The polymer matrix has been loaded with pure NIC or with NIC and CD at different ratios and release kinetics evaluated. Release profiles have shown that the presence of CD significantly affected drug delivery by decreasing the effective diffusivity of NIC. The higher the CD/NIC ratio the slower is the release. This effect has been interpreted on the basis of the proposed model and physically sound assumptions.