1,721,008 research outputs found
Synthesis and prelimary docking studies of new colchicine-benzotriazole hybrid compounds
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Successful Dendrimer and Liposome-Based Strategies to Solubilize an Antiproliferative Pyrazole Otherwise Not Clinically Applicable
No full textWater-soluble formulations of the pyrazole derivative 3-(4-chlorophenyl)-5-(4-nitrophenylamino)-1H-pyrazole-4-carbonitrile (CR232), which were proven to have in vitro antiproliferative effects on different cancer cell lines, were prepared by two diverse nanotechnological approaches. Importantly, without using harmful organic solvents or additives potentially toxic to humans, CR232 was firstly entrapped in a biodegradable fifth-generation dendrimer containing lysine (G5K). CR232-G5K nanoparticles (CR232-G5K NPs) were obtained with high loading (DL%) and encapsulation efficiency (EE%), which showed a complex but quantitative release profile governed by Weibull kinetics. Secondly, starting from hydrogenated soy phosphatidylcholine and cholesterol, we prepared biocompatible CR232-loaded liposomes (CR232-SUVs), which displayed DL% and EE% values increasing with the increase in the lipids/CR232 ratio initially adopted and showed a constant prolonged release profile ruled by zero-order kinetics. When relevant, attenuated total reflectance Fourier transformed infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM) and dynamic light scattering (DLS) experiments, as well as potentiometric titrations completed the characterization of the prepared NPs. CR232-G5K NPs were 2311-fold more water-soluble than the pristine CR232, and the CR232-SUVs with the highest DL% were 1764-fold more soluble than the untreated CR232, thus establishing the success of both our strategies
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
Hydrophilic and amphiphilic water-soluble dendrimer formulations of a not-soluble thiocarbamate derivative with moderate anti HIV activity for biomedical applications.
No full textThe engineered technology known as Drug delivery concerns the approaches, formulations, technologies and systems for transporting therapeutics in the body and delivering them as needed. Advanced controlled Drug Delivery Systems (DDSs) able to release an effective load of drug and to maintain its concentration for long time in a limited area around the target site have been developed. These “smart” DDSs allowed to reduce dosages, administrations frequency and drugs toxicity and to improve therapeutic efficacy. Nanosized and dendritic polycationic polymers such as PAMAMs are the most exploited materials for getting advanced smart DDSs and can covalently bind or encapsulate drugs. However, the high number of protonable nitrogen atoms widespread on the whole matrix involves high cytotoxicity. The modern research is increasingly oriented towards the use of not charged dendrimer scaffolds decorated with biocompatible amino acids protonable at physiological pH. Thiocarbamate 1 (Figure 1) is a non-nucleoside HIV-1 reverse transcriptase inhibitor (EC50 = 27 μM) characterized by a free carboxylic group and endowed with poor water solubility.1 With the aim at improving both its solubility and activity, derivative 1 was physically incorporated inside not-toxic amino acid-modified core-shell hydrophilic (2,3)2 and amphiphilic (4-6)3 dendrimers. The encapsulation procedure is a straightforward protocol that involves stirring derivative 1 and the starting dendrimer at r.t. in methanol (Figure 1). The obtained dendriplexes (DPXs 7-11) showed a very good DL%, a proper particle size, an adequate buffer capacity and above all were well soluble in water. Therefore, they represent an appealing and promising crew of new smart DDSs for safe in vivo clinical administrations of 1.
References:
[1] A. Spallarossa, A. Ranise, et al., Eur. J. Med. Chem. 2009, 44, 1650-1663.
[2] S. Alfei, S. Catena, 2018, submitted to Polym. Advan. Technol. 2018: https://doi.org/10.1002/pat.4396.
[3] S. Alfei, S. Catena, 2018, submitted to Polym. Int. 2018, https://doi.org: 10.1002/pi.5680
Characterization of water soluble dendrimer formulations of an insoluble thiocarbamate derivative with moderate anti HIV-1 activity: an overview
No full textDrug delivery is an engineered technology focused on the development of Drug Delivery Systems (DDSs) able to transport, release and maintain for long time the useful load of therapeutics in the body as needed for safe playing out the desired therapeutic effects. Nanosized dendritic polycationic polymers such as commercially available PAMAMs, are the most exploited materials for preparing smart DDSs, but unfortunately, the excessive cationic feature of the inner framework results in a high level of cytotoxicity. Nowadays, not charged amino acid-modified dendrimer scaffolds are considered as better solutions. These dendrimers have a more controlled number of nitrogen atoms and can be protonated at physiological pH. In order to improve the water solubility of the thiocarbamate non-nucleoside HIV-1 reverse transcriptase inhibitor 1 (Figure 1)1 five prodrugs were prepared by its entrapment inside not PAMAM amino acids-modified core-shell hydrophilic2 (Figure 2) and amphiphilic3 (Figure 3) dendrimers. As detailed in this communication an overview, organized in tables, graphs and NMR spectra of the physicochemical properties which identified obtained dendriplexes (DPXs) was provided. As estimated by NMR analysis, DPXs showed good load capacity. Mean size of their particles is suitable for avoiding rapid renal clearance while the release profile of the drug is favourable to a low spreading of drug in blood and to a massive release only within the cell. DPXs are soluble in water, EtOH and MeOH, have proper but not excessive cationic character and an optimal buffer capacity for enhanced cellular up take and pH-responsive endosomal escape once inside the cell. References: [1] A. Spallarossa, A. Ranise, et al., Eur. J. Med. Chem. 2009, 44, 1650-1663. [2] S. Alfei, S. Catena, 2018, submitted to Polym. Advan. Technol. 2018: https://doi.org/10.1002/pat.4396. [3] S. Alfei, S. Catena, 2018, submitted to Polym. Int. 2018, https://doi.org: 10.1002/pi.5680
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