Production of PEGylated Vancomycin-Loaded Niosomes by a Continuous Supercritical CO2 Assisted Process.

Niosomes are arousing significant interest thanks to their low cost, high biocompatibility, and negligible toxicity. In this work, a supercritical CO2-assisted process was performed at 100 bar and 40 °C to produce niosomes at different Span 80/Tween 80 weight ratios. The formulation of cholesterol and 80:20 Span 80/Tween 80 was selected to encapsulate vancomycin, used as a model active compound, to perform a drug release rate comparison between PEGylated and non-PEGylated niosomes. In both cases, nanometric vesicles were obtained, i.e., 214 ± 59 nm and 254 ± 73 nm for non-PEGylated and PEGylated niosomes, respectively, that were characterized by a high drug encapsulation efficiency (95% for non-PEGylated and 98% for PEGylated niosomes). However, only PEGylated niosomes were able to prolong the vancomycin release time up to 20-fold with respect to untreated drug powder, resulting in a powerful strategy to control the drug release rate.

Liposomes, transfersomes and niosomes: production methods and their applications in the vaccinal field.

One of the most effective strategies to fight viruses and handle health diseases is vaccination. Recent studies and current applications are moving on antigen, DNA and RNA-based vaccines to overcome the limitations related to the conventional vaccination strategies, such as low safety, necessity of multiple injection, and side effects. However, due to the instability of pristine antigen, RNA and DNA molecules, the use of nanocarriers is required. Among the different nanocarriers proposed for vaccinal applications, three types of nanovesicles were selected and analysed in this review: liposomes, transfersomes and niosomes. PubMed, Scopus and Google Scholar databases were used for searching recent papers on the most frequently used conventional and innovative methods of production of these nanovesicles. Weaknesses and limitations of conventional methods (i.e., multiple post-processing, solvent residue, batch-mode processes) can be overcome using innovative methods, in particular, the ones assisted by supercritical carbon dioxide. SuperSomes process emerged as a promising production technique of solvent-free nanovesicles, since it can be easily scaled-up, works in continuous-mode, and does not require further post-processing steps to obtain the desired products. As a result of the literature analysis, supercritical carbon dioxide assisted methods attracted a lot of interest for nanovesicles production in the vaccinal field. However, despite their numerous advantages, supercritical processes require further studies for the production of liposomes, transfersomes and niosomes with the aim of reaching well-defined technologies suitable for industrial applications and mass production of vaccines.

Destabilisation, aggregation, toxicity and cytosolic mislocalisation of nucleophosmin regions associated with acute myeloid leukemia.

Nucleophosmin (NPM1) is a multifunctional protein that is implicated in the pathogenesis of several human malignancies. To gain insight into the role of isolated fragments of NPM1 in its biological activities, we dissected the C-terminal domain (CTD) into its helical fragments. Here we focus the attention on the third helix of the NPM1-CTD in its wild-type (H3 wt) and AML-mutated (H3 mutA and H3 mutE) sequences. Conformational studies, by means of CD and NMR spectroscopies, showed that the H3 wt peptide was partially endowed with an α-helical structure, but the AML-sequences exhibited a lower content of this conformation, particularly the H3 mutA peptide. Thioflavin T assays showed that the H3 mutE and the H3 mutA peptides displayed a significant aggregation propensity that was confirmed by CD and DLS assays. In addition, we found that the H3 mutE and H3 mutA peptides, unlike the H3 wt, were moderately and highly toxic, respectively, when exposed to human neuroblastoma cells. Cellular localization experiments confirmed that the mutated sequences hamper their nucleolar accumulation, and more importantly, that the helical conformation of the H3 region is crucial for such a localization.

Considerations on evolution and healing of vertebral fractures.

Only little is known when talking about the evolution of a vertebral fracture. From the few studies available in the literature, we can deduce that the risk a vertebral compression fracture has to worsen its deformity is consistent. It is important to try to make a prognosis on how the fracture is going to heal based on the type of fracture encountered. A chapter of its own is the occurrence of a vertebral fracture non-union that is difficult to diagnose and treat, but comes along with a poor prognosis.

Extremely proximal fractures of the fifth metatarsal in the developmental age.

BACKGROUND: Numerous studies document the high incidence of this type of fracture of the foot in childhood due to the presence of the growth plate of the apophysis of the fifth metatarsal. Our aim in this study was to evaluate the presence and morphology of the growth nucleus and correlate its presence with fractures of the apophysis of the fifth metatarsal. MATERIALS AND METHODS: Between 2001 and 2003, we reviewed the radiographs of 481 patients (558 feet) between 6 months and 16 years that were diagnosed with a fracture. We evaluated for the presence and morphology of the growth nucleus of the base of the fifth metatarsal in the 7- to 16-year age group because this is the time interval in which the nucleus becomes visible radiographically. RESULTS: We identified the nucleus of the base of the fifth metatarsal in 115 patients for a total of 132 feet. A fracture of the fifth metatarsal was found in 12.8%. A misdiagnosis had been made in 47%. Misdiagnosis was strictly related to the presence of the growth nucleus of the apophysis except two cases where an accessory bone was present. CONCLUSIONS: Our study demonstrated a much higher incidence of the presence of the growth nucleus than documented in previous reports and that its morphology varied widely in relation to the stage of maturity of the patient and the radiographic technique. Its presence led to a high rate of misdiagnosis of a fracture.