Injectable supramolecular hydrogels based on custom-made poly(ether urethane)s and α-cyclodextrins as efficient delivery vehicles of curcumin.

A strategy to enhance drug effectiveness while minimizing controversial effects consists in exploiting host-guest interactions. Moreover, these phenomena can induce the self-assembly of physical hydrogels as effective tools to treat various pathologies (e.g., chronic wounds or cancer). Here, two Poloxamers®/Pluronics® (P407/F127 and P188/F68) were utilized to synthesize various LEGO-like poly(ether urethane)s (PEUs) to develop a library of tunable and injectable supramolecular hydrogels for drug delivery. Three PEUs were synthesized by chain extending Poloxamer/Pluronic with 1,6-cyclohexanedimethanol or N-Boc serinol. Other two amino-functionalized and highly responsive polymers were obtained thorough Boc-group cleavage. For hydrogel design, the spontaneous self-assembly of the poly(ethylene oxide) domains of PEUs with α-cyclodextrins was exploited to form poly(pseudo)rotaxanes (PPRs). PPR-derived channel-like crystals were characterized by X-Ray powder diffraction, Infra-Red and Proton Nuclear Magnetic Resonance spectroscopies. Cytocompatible hydrogel formulations were designed at PEU concentrations between 1% and 5% w/v and α-cyclodextrin at 10% w/v. Supramolecular gels showed good mechanical performances (storage modulus up to 20 kPa) coupled with marked thixotropic and self-healing properties (mechanical recovery over 80% within 30 s after cyclic rupture) as assessed through rheology. Hydrogels exhibited stability and high responsiveness in watery environment up to 5 days: the release of less stable components as suitable drug carriers was coupled with high swelling (doubling the content of fluids with respect to their dry mass) and shape retention. Curcumin was encapsulated into the hydrogels at high concentration (80 µg ml-1) through its complexation with α-cyclodextrins and delivery tests showed controllable and progressive release profiles up to four days.

Supramolecular hydrogels based on custom-made poly(ether urethane)s and cyclodextrins as potential drug delivery vehicles: design and characterization.

The design of supramolecular (SM) hydrogels based on host-guest complexes represents an effective strategy to develop drug delivery systems. In this work, we designed SM hydrogels based on α-cyclodextrin and high-molar mass amphiphilic poly(ether urethane)s (PEUs, ) based on Poloxamer® 407 and differing in their chain extender. The successful formation of poly(pseudo)rotaxanes and their supramolecular interactions were chemically demonstrated. Then, self-healing (80-100% mechanical recovery) supramolecular hydrogels were developed by mixing PEU and α-cyclodextrin solutions at different concentrations. Stability in physiological-like environment and mechanical properties improved with increasing α-cyclodextrin content (9-10% w/v), meanwhile gelation time decreased. A synergistic effect of poly(pseudo)rotaxanes crystals and PEU micellar structures on gel properties was observed: the first were predominant at low PEU concentrations (1-5% w/v), while the latter prevailed at high PEU concentrations (7-9% w/v). Increasing PEU concentration led to gels with increased dissolution rate, not-fully developed networks and slight cytotoxicity, meanwhile residence time in aqueous media improved (>7 d). At low PEU concentrations (1-5% w/v), cytocompatible gels (100% cell viability) were obtained, which maintained their shape in aqueous medium up to 5 d and completely dissolved within 7 d. PEU chemical composition affected PEU/α-cyclodextrin interactions, with longer gelation time and lower mechanical properties in gels based on PEU with pendant functionalities. Gels progressively released a model molecule (fluorescein isothiocyanate-dextran) within 3-4 days with no initial burst release. We thus demonstrated the suitability of custom-made PEUs as constituent of SM hydrogels with α-cyclodextrin and the high potential of the resulting systems for drug delivery applications.

Fretting Fatigue Analysis of Additively Manufactured Blade Root Made of Intermetallic Ti-48Al-2Cr-2Nb Alloy at High Temperature.

Slots in the disk of aircraft turbines restrain the centrifugal load of blades. Contact surfaces between the blade root and the disk slot undergo high contact pressure and relative displacement that is the typical condition in which fretting occurs. The load level ranges from zero to the maximum during take-off. This cycle is repeated for each mission. In this paper, a fretting fatigue analysis of additively manufactured blades is presented. Blades are made of an intermetallic alloy γTiAl. Fretting fatigue experiments were performed at a frequency of 0.5 Hz and at a temperature of 640 °C to match the operating condition of real blades. The minimum load was fixed at 0.5 KN and three maximum loads were applied, namely 16, 18 and 20 kN. Both an analytical and a two-dimensional finite element model were used to evaluate the state of stress at the contact interfaces. The results of the analytical model showed good agreement with the numerical model. Experiments showed that cracks nucleate where the analytical model predicts the maximum contact pressure and the numerical model predicts the maximum equivalent stress. A parametric analysis performed with the analytical model indicates that there exists an optimum geometry to minimize the contact pressure. Tests showed that the component life changed dramatically with the maximum load variation. Optical topography and scanning electron microscopy (SEM) analysis reveals information about the damage mechanism.