1,721,037 research outputs found
Biomedical gels: structure and properties
No full textBiomedical hydrogels are defined as biocompatible solid-liquid systems in which polymeric chains (fibers) are crosslinked to form a 3D-network swollen by a huge water amount. Their use as controlled drug release systems is in continuous growth. However, a critical step in their development is the characterization of their 3D nano/micro structure and the correlation with fabrication parameters. Indeed, hydrogels structure is complex and depends on fibers diameter, concentration, mesh/pore size and degree of crosslinking. Historically, hydrogel structure have been imaged using AFM, SEM, TEM and X-ray microscopy. Although these methods provide high-resolution images, they require a significant sample manipulation that can lead to shrinkage and collapse of the fibers structure. Moreover, information is strictly localized and poorly suited for bulk properties. The target of this thesis is to propose the combined use of not-destructive, economic and fast technologies like rheology and low field NMR (LF-NMR) to understand the macro-, micro- and nanoscopic characteristic of several hydrogels. We aim to drastically reduce the need for time-consuming, expensive measurement, rather to select optimal sample for more complex characterization.
Reliability of rheological and LF NMR approach were tested to:
• follow hydrogel gelation process in i) a sonicated nanocellulose solution ii) a thermo-sensitive chitosan gel. In particular, the effect of i) salt addition and sonicated time and ii) temperature on the gelation process were considered, respectively.
• interpret the characteristics of cross-linked gels system relaying on polymer blends [PVP (poly-vinyl-pirrolidone) and alginate]. In particular gels mechanical strength, 3D nano/micro structure and mesh size distribution were determined. Some of these systems, suitable for liposomes delivery, were also characterized by TEM and this technique confirmed our findings.
• correlate mesh size and release rate in a Diels-Alder poly(ethylene glycol) based hydrogel for controlled antibodies release. Our estimations well fitted with test of in vitro release of fluorescein isothiocyanate labeled Dextran and Bertuzimab.
For what concerns biological tissues, the focus is on two innovative applications of LF-NMR relying on the different conditions experienced by water confined in three-dimensional structures. Indeed, from the LF-NMR point of view, we can distinguish between free water that is not affected by the solid surface, and bound water that undergoes the effect of solid surface:
• The first application considers the analysis on the expectorate of patients affected by cystic fibrosis (CF). This pulmonary disease is mainly characterized by a dehydrated and hyper concentrated mucus in airways. We analysed these voluntary samples to reveal mucus dehydration and pathological components, which are strictly correlated to disease severity. As this approach is less expensive, faster, non-invasive and does not require highly qualified personnel, it has the potential to become a valuable monitoring tool.
• The second application regards the evaluation of trabecular bone extracts from osteoporosis and osteoarthrosis patients who underwent hip replacement. These two pathological conditions differ for the quality of bone tissue, and both of them are typical of elders. Water mobility inside the trabecular network is connected to the pore size distribution characterising the bone tissue. Therefore we expected that osteoporosis samples present higher water mobility than osteoarthrosis ones. It could be a new method to rapidly and easily know the severity of osteoporosis
Towards a universal size distribution in a polymer network. Implications for drug delivery and plasmonic nanoparticle transport phenomena in polysaccharide and synthetic hydrogels
Full text linkPolymeric hydrogels are paramount to outstanding applications in materials science, biology, medicine, pharmacy. Their similarity to living tissues is leveraged in clinical branches (oncology, cardiology, immunology, neurology, wound healing) for delivering a large range of drugs (encompassing DNA, RNA, protein molecules) and realizing in-vivo models of stimuli-responsive or controlled drug release. Rubber elasticity theory and the swollen network hypothesis are key for properly designing the geometric and mechanical features of hydrogels and polymer networks. The assumption of a Gaussian distribution of end-to-end lengths in a polymer molecule, however, can break down in several cases. Here, strongly supported by Low field NMR and rheology experiments, we propound the generalized Weibull law of extreme value statistics (EVS) to have universal validity in hydrogel materials. Mesh size values that account for an intrinsic statistical dependence between monomeric positions (or stiffness) show much better agreement with measurements conducted on physically crosslinked samples (agar, alginate and scleroglucan), including sputum specimens (rich in mucins) from patients affected by chronic respiratory conditions (cystic fibrosis) and on chemically crosslinked samples (poly-vinylpyrrolidone, PVP; poly-(ethylene-glycol/propylene-glycol), PEG/PPG). Across all ten gels, the Gaussian distribution yields the smallest average mesh size, ranging roughly from 7 nm for the densest alginate 2 % (9 gL−1) hydrogel to about 80 nm for one of the sputum. Working with the pierced Gaussian inflates the mesh size to ≈1.5 × the Gaussian value, with increases from a modest +4 % in alginate 1 % up to nearly +100 % in the open PVP network (48 → 98 nm). The generalized Weibull distribution usually falls between the two Gaussians, yet in agar 1 % and scleroglucan 2 % it overtakes the pierced Gaussian (e.g. 20.2 > 15.8 nm for agar 1 %), reflecting a strong heavy-tailed distribution. The predicted mesh order therefore is Gaussian < generalized Weibull ≈ pierced Gaussian, with the precise ranking ruled by the width and skewness of each network statistics. Overall, our findings – being straightforward to apply – will profoundly impact on the description, conception and control of polymer networks, which often demand advanced instrumental techniques for compensating the lack of adequate predictive models. Among other relevant implications, aside from drug delivery, we highlight the characterization of the photothermal (or thermoplasmonic) response of hydrogel matrices hosting metal nanoparticles (e.g. with applications in hyperthermia cancer treatment and enhanced chemical processes). On the theoretical side, we emphasize the study of transport and thermomechanical properties of polymeric networks
Rheology of Laponite-scleroglucan hydrogels
No full texttBoth 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. Whenattractive and repulsive interparticle interactions are so effective that they lead to arrested states (attrac-tive gel or repulsive glass), the rheological behavior of the dispersion undergoes a sharp transition, fromquasi-Newtonian to markedly shear thinning and viscoelastic. Conversely, scleroglucan solutions grad-ually change to weak gels with increasing polymer concentration. The present work is concerned withaqueous Laponite-scleroglucan mixed systems, obtained according to different preparation modes, andis aimed at examining how much the content and proportion of both components affect the viscoelasticand flow properties of the mixed syste
Proprietà reologiche di dispersioni di laponite in matrici acquose di scleroglucano
No full textBoth laponite and scleroglucan can find several applications in various fields (from industrial to biomedical 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 interactions are so effective that they lead to generate arrested states (attractive gel or repulsive glass), the rheological behavior of the dispersion undergoes a sharp transition, from quasi-Newtonian to markedly shear thinning and viscoelastic. Conversely, scleroglucan solutions gradually change to weak gel behavior with increasing polymer concentration. The present work is concerned with aqueous laponite-scleroglucan systems, obtained according to different preparation modes, and is aimed at examining how much the content and proportion of both components affect the viscoelastic and flow properties of the mixed syste
Evaluation of concentration and dispersion of functionalized carbon nanotubes in aqueous media by means of Low Field Nuclear Magnetic Resonance
No full textDispersions of functionalized carbon nanotubes (fx-CNTs) have been analyzed by means of Low Field Nuclear Magnetic Resonance measurements (LF-NMR). This technique showed that the presence of the fx-CNTs strongly influences the structuring of the water molecules. Thereupon, the water transversal relaxation rate (r2) can be used to get information about the concentration of the CNTs in aqueous dispersion and their aggregation tendency. Finally, the effect of the addition of an anionic polyelectrolyte, namely alginate, on aqueous dispersion of CNTs was explored by using LF-NMR, which revealed different dependence of r2 from CNT concentration, depending on the type and charge of fx-CNTs
Insight into the ionotropic gelation of chitosan using tripolyphosphate and pyrophosphate as cross-linkers
No full textIonotropic gelation of chitosan by means of opposite charged ions represents an efficient alternativeto covalent reticulation because of milder condition of use and, in general, higher biocompatibility ofthe resulting systems. In this work 90◦light scattering (turbidimetry), circular dichroism (CD) and1HNMR measurements have been performed to study the interactions between the biopolymer and ioniccross-linkers tripolyphosphate (TPP) and pyrophosphate (PPi) in dilute solutions. Thereafter, a dialysis-based technique was exploited to fabricate tridimensional chitosan hydrogels based on both polyanions.Resulting matrices showed a different mechanical behavior because of their peculiar mesh-texture atmicro/nano-scale: in the present contribution we demonstrate that TPP and PPi favor the formation ofhomogeneous and inhomogeneous systems, respectively. The different texture of networks could beexploited in future for the preparation of systems for the controlled release of molecule
2D DYNAMICAL SIMULATION OF A VIBRATIONAL MILL
No full text2D DYNAMICAL SIMULATION OF A VIBRATIONAL MIL
Mathematical modeling of drug release from natural polysaccharides based matrices
No full textThe 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 deliver
Injectable Chitosan/β-Glycerophosphate System for Sustained Release: Gelation Study, Structural Investigation, and Erosion Tests
No full textHydrogels can constitute reliable delivery systems of drugs, including those based on nucleic
acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response
to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active
molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this
study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its
use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release
of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration
on the gelation temperature. We then found the “optimized composition”, namely, the one in which the
Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic
resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded
drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor
their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking
a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is
deemed to be an ideal candidate as injectable gelling material for a sustained relea
The role of the transcription factor E2F1 in hepatocellular carcinoma
No full textHepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death. Because of the fast growth, early hepatic metastasis and the multidrug resistance, the five-year survival rate is very low. Thus, the understanding of its biology can significantly contribute in identifying valuable targets for novel therapeutic approaches. In this regard, E2F1 may represent an interesting candidate. E2F1 is a transcription factor implicated in the regulation of many cellular processes including cell proliferation and apoptosis. Whereas the involvement of E2F1 in HCC has been recognized, its ability to act as a proliferative and/or apoptotic factor in HCC has not yet been clarified and, in this regard, an active debate is ongoing. The definition of E2F1 role in HCC is not a trivial aspect as it can have significant consequences for the development of novel therapeutic options with E2F1 as target. In this review, we present data about the reported proliferative/apoptotic effects as well as the dual (combined proliferation and apoptosis) functions of E2F1 in HCC discussing
the molecular basis for this behavior. The data available so far indicate that the proliferative and apoptotic functions of E2F1 in HCC may coexist but the proliferative effect seems to be more pronounced than the apoptotic one
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