Silk Fibroin: a biopolymer platform for innovative pharmaceutical formulation and biomedical devices.

The protein silk fibroin (SF) from the silkworm Bombyx mori is a FDA-approved biomaterial used over centuries as sutures wire. Importantly, several evidences highlighted the potential of silk biomaterials obtained by using so-called regenerated silk fibroin (RSF) in biomedicine, tissue engineering and drug delivery. Indeed, by a water-based protocol, it is possible to obtain protein water-solution, by extraction and purification of fibroin from silk fibres. Notably, RSF can be processed in a variety of biomaterials forms used in biomedical and technological fields, displaying remarkable properties such as biocompatibility, controllable biodegradability, optical transparency, mechanical robustness. Moreover, RSF biomaterials can be doped and/or chemical functionalized with drugs, optically active molecules, growth factors and/or chemicals In this view, activities of my PhD research program were focused to standardize the process of extraction and purification of protein to get the best physical and chemical characteristics. The analysis of the chemo-physical properties of the fibroin involved both the RSF water-solution and the protein processed in film. Chemo-physical properties have been studied through: vibrational (FT-IR and Raman-FT) and optical (absorption and emission UV-VIS) spectroscopy, nuclear magnetic resonance (1H and 13C NMR), thermal analysis and thermo-gravimetric scan (DSC and TGA). In the last year of my PhD, activities were focused to study and define innovative methods of functionalization of the silk fibroin solution and films. Indeed, research program was the application of different methods of manufacturing approaches of the films of fibroin without the use of harsh treatments and organic solvents. New approaches to doping and chemical functionalization of the silk fibroin were studied. Two different methods have been identified: 1) biodoping that consists in the doping of fibroin with optically active molecules through the addition of fluorescent molecules in the standard diet used for the breeding of silkworms; 2) chemical functionalization via silylation

Exaggerated QT prolongation after cardioversion of atrial fibrillation

AbstractOBJECTIVESThe purpose of this study was to test the hypothesis that the extent of drug-induced QT prolongation by dofetilide is greater in sinus rhythm (SR) after cardioversion compared with during atrial fibrillation (AF).BACKGROUNDAnecdotes suggest that when action potential–prolonging antiarrhythmic drugs are used for AF, excessive QT prolongation and torsades de pointes (TdP) often occur shortly after sinus rhythm is restored.METHODSQT was measured in nine patients with AF who received two identical infusions of dofetilide: 1) before elective direct current cardioversion and 2) within 24 h of restoration of SR.RESULTSDuring AF, dofetilide did not prolong QT (baseline: 368 ± 48 ms vs. drug: 391 ± 60, p = NS) whereas during SR, QT was prolonged from 405 ± 55 to 470 ± 67 ms (p < 0.01). In four patients (group I), the SR dofetilide infusion was terminated early because QT prolonged to >500 ms, and one patient developed asymptomatic nonsustained TdP. The remaining five patients (group II) received the entire dose during SR. Although ΔQT was greater in group I during SR (91 ± 22 vs. 45 ± 25 ms, p < 0.05), plasma dofetilide concentrations during SR were similar in the two groups (2.72 ± 0.96 vs. 2.77 ± 0.25 ng/ml), and in AF (2.76 ± 1.22 ng/ml). ΔQT in SR correlated inversely with baseline SR heart rate (r = −0.69, p < 0.05), and QT dispersion developing during the infusion (r = 0.79, p < 0.01).CONCLUSIONSShortly after restoration of SR, there was increased sensitivity to QT prolongation by this IKr-specific blocker. Slower heart rates after cardioversion and QT dispersion during treatment appear to be important predictors of this response

Cardiovascular risk factors in postmenopausal women: effects of estrogen therapy on glucose and lipid profiles

The menopause is associated with unfavorable changes in the lipid profile as well as in glucose metabolism, which may help to increase the incidence of cardiovascular diseases. The metabolic impact of hormone replacement therapy differs in relation to the dose of the estrogen component, the type of progestin, and the route of administration used. Since most studies analyze the effect of combined estro-progestin therapy, the impact of the estrogen component alone is not always differentiable, however the main results are generally consistent. A review of the recent literature was conducted to analyze the impact of estrogen replacement therapy (ERT) on glucose and lipid metabolism and the differences linked to different doses, associations and routes of administration. Studies were selected on the basis of quality of data and relevance to the present topic. Many studies showed that both oral and transdermal estrogen therapy induced positive effects on glucose metabolism, with minimal changes and differences between treatments. A considerable amount of data documented increases in HDL and decreases in LDL cholesterol. Low-dose estrogen therapy showed no negative effect on triglycerides and a neutral effect on the whole lipid panel. In conclusion, low-dose ERT may prevent the physiological worsening of glucose and lipid metabolism in menopausal women without showing any significant negative effect

Keratin-hydrotalcites hybrid films for drug delivery applications

In this work novel hybrid materials for drug delivery purposes are obtained by combining keratin with hydrotalcite nanoparticles containing diclofenac. The hybrid films showed a less pronounced swelling, porosity and degradation and a greater thermal stability compared to pure keratin films containing free diclofenac. These results, together with the slight shift towards smaller wavelength numbers of amide I band led to the hypothesis of a probable cross-linking between hydrotalcites and the protein mediated by glutaraldehyde, which results in a total reinforcing action on the hybrid material. In addition, diclofenac release profiles of the hybrid film in physiological conditions were higher than those of the non-hybrid compound. Furthermore, keratin/hydrotalcite were able to support fibroblast cells adhesion and growth suggesting their potential use as drug delivery systems for wound healing and tissue engineering application

Innovative Multifunctional Silk Fibroin and Hydrotalcite Nanocomposites: A Synergic Effect of the Components

Novel hybrid functional materials are formed by combining hydrotalcite-like compounds and silk fibroin (SF-HTlc) via an environmental friendly aqueous process. The nanocomposites can be prepared with different weight ratio of the constituting components and preserve the conformational properties of the silk protein and the lamellar structure of hydrotalcites. Optical microscopy, scanning electron microscopy, and atomic force microscopy analyses show a good dispersion degree of the inorganic nanoparticles into the organic silk matrix. A mutual benefit on the stability of both organic and inorganic components was observed in the nanocomposites. SF-HTlc displayed limited dissolution of hydrotalcite in acidic medium, enhanced mechanical properties, and higher protease resistance of silk protein. The transparency, flexibility, and acidic environment resistance of silk fibroin combined to the protective and reinforcing properties of hydrotalcites generate a hybrid material, which is very attractive for applications in recently reported silk based opto-electronic and photonics technologies

Integration of a silk fibroin based film as a luminescent down-shifting layer in ITO-free organic solar cells

We report here a study on the integration of the silk fibroin (SF) protein in organic solar cells. The intrinsic low toxicity, natural availability, biodegradability, water processing, good film forming properties and capability to be doped with functional molecules of SF biopolymer inspired us to integrate it as a transparent and inert or functional bottom layer in organic solar cells. Water stable, optically transparent, smooth and homogeneous SF thin films (thickness ∼400 nm) were successfully prepared on glass and characterized. Then ITO-free bulk heterojunction (BHJ) solar cells employing P3HT:PC61BM as a standard active layer and a highly conductive PEDOT:PSS formulation as a semi-transparent anode were deposited over the SF films. As a result, the power conversion efficiency (PCE) of all silk-integrated BHJ solar cells was comparable to the references on bare glass. The ability of SF to act as a host matrix for functional moieties was exploited to give to the SF layer the functionality of a Luminescent Down-shifting film (LDS), as confirmed by the spectral response measurements, by using a water soluble stilbene derivative (Stb). The photovoltaic performance of all SF-based devices was significantly stable over time, overcoming the problems of the ITO-based reference cells after 70 days. Finally, flexible SF-integrated ITO-free solar cells were successfully fabricated on PET substrates

Mild and Effective Polymerization of Dopamine on Keratin Films for Innovative Photoactivable and Biocompatible Coated Materials

Mussel-inspired polydopamine (PD) coating represents a promising route for constructing functional materials and finely tuning or completely changing their surface properties. In this work, a mild and effective method to realize the deposition of PD on keratin-based films is reported. Reactive oxygen species (ROS), generated by keratin films doped with a photosensitizer, e.g., Azure A (AzA), upon UV-vis and vis-near IR irradiation, are exploited to obtain the PD coating. Interestingly, the use of vis-near IR irradiation leads to an increased production of ROS by AzA resulting in a greater PD deposition. Compared to uncoated keratin films, the PD-keratin coated materials show a granular but homogeneous surface and an increased hydrophilicity, maintaining the ROS generation ability of AzA. This work demonstrates a useful method to effectively and rapidly functionalize with PD materials that are sensitive to temperature, pH and UV light, such as keratin. The proposed strategy allows obtaining new multifunctional biomaterials of potential interest in tissue engineering and drug delivery; in particular, the use of PD-keratin films for near IR laser bonding of ophthalmic tissue, which is a representative case in wound healing purpose, is shown

Naturally functionalized silk as useful material for photonic applications

none15noSilk is a natural fibre obtained from the Bombyx mori silkworm cocoons that can be used in a wide range of fields thanks to its inherent multifunctionality. Post-production steps are necessary to impart colour to the fibres to employ the material for optics and photonic applications, such as in fluorescence-based optofluidic devices in lab-on-a-chip realization. Here we present an intrinsically greener dyeing approach for fabricating naturally functionalized silk, where highly-fluorescent organic dyes with lasing properties are in vivo up-taken by silkworms once introduced in the artificial diet. A detailed photoluminescence spectroscopy investigation is implemented to test whether the dyes are effectively incorporated within the silk proteins, in correlation with the silkworm gland positions where proteins extraction is held. Light amplification characteristics are demonstrated in silk extracted from glands of silkworm fed with artificial diet doped with Rhodamine B dye.mixedSusanna Cavallini; Stefano Toffanin; Camilla Chieco; Anna Sagnella; Francesco Formaggio;Assunta Pistone ; Tamara Posati d; Marco Natali; Marco Caprini; Valentina Benfenati;Nicola Di Virgilio; Giampiero Ruani; Michele Muccini; Roberto Zamboni; Federica RossiSusanna Cavallini; Stefano Toffanin; Camilla Chieco; Anna Sagnella; Francesco Formaggio;Assunta Pistone ; Tamara Posati d; Marco Natali; Marco Caprini; Valentina Benfenati;Nicola Di Virgilio; Giampiero Ruani; Michele Muccini; Roberto Zamboni; Federica Ross