1,721,000 research outputs found
Nanomedicines for brain diseases: Where we are and where we are going
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Development and validation of a new storage procedure to extend the in-use stability of azacitidine in pharmaceutical formulations
Full text linkStability studies performed by the pharmaceutical industry are principally designed to fulfill licensing requirements. Thus, post-dilution or post-reconstitution stability data are frequently limited to 24 h only for bacteriological reasons, regardless of the true physicochemical stability which could, in many cases, be longer. In practice, the pharmacy-based centralized preparation may require preparation in advance for administration, for example, on weekends, holidays, or in general when pharmacies may be closed. We report an innovative strategy for storing resuspended solutions of azacitidine, a well-known chemotherapic agent, for which the manufacturer lists maximum stability of 22 h. By placing the syringe with the azacitidine reconstituted suspension between two refrigerant gel packs and storing it at 4 °C, we found that the concentration of azacitidine remained above 98% of the initial concentration for 48 h, and no change in color nor the physicochemical properties of the suspension were observed throughout the study period. The physicochemical and microbiological properties were evaluated by HPLC–UV and UHPLC-HRMS analysis, FTIR spectroscopy, pH determination, visual and subvisual examination, and sterility assay. The HPLC-UV method used for evaluating the chemical stability of azacitidine was validated according to ICH. Precise control of storage temperature was obtained by a digital data logger. Our study indicates that by changing the storage procedure of azacitidine reconstituted suspension, the usage window of the drug can be significantly extended to a time frame that better copes with its use in the clinical environment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Nanoparticles engineered with Rituximab and loaded with Nutlin-3 show promising therapeutic activity in B leukemic xenografts
No full textPURPOSE: Since the non-genotoxic inhibitor of the p53/MDM2 interactions Nutlin-3 has shown promising in vitro therapeutic activity against a variety of p53wild-type cancer cells, in this study we evaluated an innovative strategy able to specifically target Nutlin-3 towards CD20+ malignant cells.
EXPERIMENTAL DESIGN: The cytotoxic effects of Nutlin-3 encapsulated into poly(lactide-co-glycolide) nanoparticles (NP-Nut) and into Rituximab (anti-CD20 Antibody)-engineered NP (NP-Rt-Nut) as well as of nanoparticles engineered with Rituximab alone (NP-Rt) were initially analyzed in vitro in JVM-2 B-leukemic cells, by assessing both the functional activation of the p53 pathway (by Nutlin-3) and/or the activation of the complement cascade (by Rituximab). Moreover, the potential therapeutic efficacy of NP-Nut, NP-Rt and NP-Rt-Nut were comparatively assessed in vivo in CD20+ JVM-2 leukemic xenograft SCID mice.
RESULTS: Functional in vitro assays demonstrated that NP-Nut and NP-Rt-Nut exhibited a comparable ability to activate the p53 pathway in the p53wild-type JVM-2 leukemic cells. On the other hand, NP-Rt and NP-Rt-Nut, but not NP nor NP-Nut, were able to promote activation of the complement cascade. Of note, the in vivo intra-tumoral injection in JVM-2 B leukemic/xenograft mice demonstrated that NP-Rt-Nut displayed the maximal therapeutic activity promoting a survival rate significantly higher not only with respect to control animals, treated either with vehicle or with empty NP, but also with respect to animals treated with NP-Nut or NP-Rt.
CONCLUSIONS: Our data demonstrate for the first time the potential anti-leukemic activity of Rituximab-engineered Nutlin-3 loaded NP in xenograft SCID mice
Curcumin loaded polymeric vs. Lipid nanoparticles: Antioxidant effect on normal and hypoxic olfactory ensheathing cells
Full text linkBackground: Curcumin (Cur) shows anti-inflammatory and antioxidant effects on central nervous system diseases. The aim of this study was to develop Cur-loaded polymeric and lipid nanoparticles for intranasal delivery to enhance its stability and increase antioxidant effect on olfactory ensheathing cells (OECs). Methods: The nanosuspensions were subjected to physico-chemical and technological evaluation through photon correlation spectroscopy (PCS), differential scanning calorimetry (DSC) and UV-spectrophotometry. The cytotoxicity studies of nanosuspensions were carried out on OECs. A viability test was performed after 24 h of exposure of OECs to unloaded and curcumin-loaded nanosuspensions. The potential protective effect of Cur was assessed on hypoxic OECs cells. Uptake studies were performed on the same cell cultures. Thermal analysis was performed to evaluate potential interaction of Cur with a 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) biomembrane model. Results: PCS analysis indicated that lipid and polymeric nanosuspensions showed a mean size of 127.10 and 338.20 nm, respectively, high homogeneity and negative zeta potential. Incorporation of Cur into both nanocarriers increased drug stability up to 135 days in cryoprotected freeze-dried nanosuspensions. Cell viability was improved when hypoxic OECs were treated with Cur-loaded polymeric and lipid nanosuspensions compared with the control. Conclusions: Both nanocarriers could improve the stability of Cur as demonstrated by technological studies. Biological studies revealed that both nanocarriers could be used to deliver Cur by intranasal administration for brain targeting
Development, optimization and characterization of Eudraguard®-based microparticles for colon delivery
Full text linkDevelopment of pH-dependent systems for colon delivery of natural active ingredients is an attractive area of research in the field of nutraceutical products. This study was focused on Eudraguard® resins, that are methacrylate copolymers approved as “food grade” by European Commission and useful for the production of food supplements. In particular, Eudraguard® Biotic (EUG-B), characterized by a pH-dependent solubility and Eudraguard® Control (EUG-C), whose chemical properties support a prolonged release of the encapsulated compounds, were tested. To obtain EUG microparticles, different preparation techniques were tested, in order to optimize the preparation method and observe the effect upon drug encapsulation and specific colonic release. Unloaded microparticles were initially produced to evaluate the influence of polymer characteristics on the formulation process; subsequently microparticles loaded with quercetin (QUE) as a low solubility model drug were prepared. The characterization of microparticles in the solid-state (FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry) indicated that QUE was uniformly dispersed in a non-crystalline state in the polymeric network, without strong signs of chemical interactions. Finally, to assess the ability of EUG-C and EUG-B to control the drug release in the gastric environment, and to allow an increased release at a colonic level, suitable in vitro release tests were carried out by simulating the pH variations along the gastro-intestinal tract. Among the evaluated preparation methods, those in which an aqueous phase was not present, and in particular the emulsion-solvent evaporation method produced the best microparticle systems. The in vitro tests showed a limited drug release at a gastric level and a good specific colon release
Advantages and challenges of polymer-lipid hybrid nanoparticles for the delivery of biotech drugs
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