Multidrug Idebenone/Naproxen Co-loaded Aspasomes for Significant in vivo Anti-inflammatory Activity

The use of proper nanocarriers for dermal and transdermal delivery of anti-inflammatory drugs recently gained several attentions in the scientific community because they pass intact and accumulate payloads in the deepest layers of skin tissue. Ascorbyl palmitate-based vesicles (aspasomes) can be considered a promising nanocarrier for dermal and transdermal delivery due to their skin whitening properties and suitable delivery of payloads through the skin. The aim of this study was the synthesis of multidrug Idebenone/naproxen co-loaded aspasomes for the development of an effective anti-inflammatory nanomedicine. Aspasomes had suitable physicochemical properties and were safe in vivo if topically applied on human healthy volunteers. Idebenone/naproxen co-loaded aspasomes demonstrated an increased therapeutic efficacy of payloads compared to the commercially available Naprosyn® gel, with a rapid decrease of chemical-induced erythema on human volunteers. These promising results strongly suggested a potential application of Idebenone/naproxen multidrug aspasomes for the development of an effective skin anti-inflammatory therapy.     

Bone Marrow-Mesenchymal Stromal Cell Secretome as Conditioned Medium Relieves Experimental Skeletal Muscle Damage Induced by Ex Vivo Eccentric Contraction

Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34⁺ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine.     

Assessment of biodiesel blending detection capability of the on-board diagnostic of the last generation automotive diesel engines

Results of a research project aimed at studying the capability to develop a method (economic and simple) for on-board biodiesel blending detection are described. The method is based on the direct measurement of the Indicated Mean Effective Pressure (IMEP).The study was carried out on a 2.0L four-cylinder “torque-controlled” Euro 5 diesel engine for passenger car (PC) application. This engine, equipped with instrumented glow plug for combustion closed-loop control, represents the state of the art of the diesel engine control technology.Two biodiesels were chosen for the experiments: a rapeseed methyl-ester (RME) and an aged RME, while the conventional diesel fuel was an European (EU) certification diesel fuel.Results indicate generally a good response in blending detection of the method. However, in order to attain an acceptable accuracy, a pre-calibration appears necessary.     

New Evidence for Cross Talk between Melatonin and Mitochondria Mediated by a Circadian-Compatible Interaction with Nitric Oxide

Extending our previous observations, we have shown on HaCat cells that melatonin, at ~10⁻⁹ M concentration, transiently raises not only the expression of the neuronal nitric oxide synthase (nNOS) mRNA, but also the nNOS protein synthesis and the nitric oxide oxidation products, nitrite and nitrate. Interestingly, from the cell bioenergetic point of view, the activated NO-related chemistry induces a mild decrease of the oxidative phosphorylation (OXPHOS) efficiency, paralleled by a depression of the mitochondrial membrane potential. The OXPHOS depression is apparently balanced by glycolysis. The mitochondrial effects described have been detected only at nanomolar concentration of melatonin and within a time window of a few hours’ incubation; both findings compatible with the melatonin circadian cycle.     

β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.     

Microstructural characterization and in vitro bioactivity of porous glass-ceramic scaffolds for bone regeneration by synchrotron radiation X-ray microtomography

One of the key purposes of bone tissue engineering is the development of new biomaterials that can stimulate the body's own regenerative mechanism for patient's anatomical and functional recovery. Bioactive glasses, due to their versatile properties, are excellent candidates to fabricate porous 3-D architectures for bone replacement. In this work, morphological and structural investigations are carried out on Bioglass^®- and CEL2-derived scaffolds produced by sponge replication (CEL2 is an experimental glass developed at Politecnico di Torino). Synchrotron radiation X-ray microtomography is used to study the samples 3-D architecture, pores size, shape, distribution and interconnectivity, as well as the growth kinetics on scaffolds struts of a newly formed apatitic phase during in vitro treatment in simulated body fluid, in order to describe from a quantitative viewpoint the bioactive potential of the analyzed biomaterials. An accurate comparison between architectural features and bioactive behaviour of Bioglass^®- and CEL2-derived scaffolds is presented and discussed.