1,720,979 research outputs found
Design and Development of Novel Biocompatible Nanosystems for Drug Delivery
Full text linkIn recent years, pharmaceutical research has focused on the development on nanotechnology systems applicable in different fields of medicine, especially in the field of drug delivery. Nanotechnology is an emerging branch of sciences for designing tools and devices of nanoscale size with specific function at the cellular, atomic and molecular levels. Nanocarriers, owing to their high surface area volume ratio, have the ability to alter basic properties and bioactivity of drugs. Improved the pharmacokinetics and biodistribution, decreased toxicities, improved solubility and stability, controlled release and site-specific delivery of therapeutic agents are some of the features that nanocarriers can incorporate in drug delivery system. The composition of the nanocarriers, (e. g. organic, inorganic, and hybrid materials) and the form in which drugs are associated with them, such as core-shell system or matrix system, are also fundamental for understanding their drug delivery profile.
Considering the above facts, this dissertation aims to design novel nano-based drug delivery systems and to develop new control process strategies, such as modified the shape, chemical composition, internal structure and morphology of the nanocarriers so as to obtain new levels of product performance in the targeted drug delivery system.
Firstly, we designed a new nano-formulations to enhance the therapeutic efficacy and bioavailability of ocular drugs, for glaucoma therapy. An amphiphilic di-block copolymer, composed of methoxy poly(ethylene glycol) (mPEG) and poly(-caprolactone) (PLC), that can self-assemble into polymeric micelles (PMs), was synthesized. mPEG-PLC PMs bearing the hydrophobic drug, Methazolamide (MTZ) were formulated and fully characterized. In vitro and in vivo studies were carried out to verify ocular tolerability and to evaluate anti-glaucoma activity in a glucocorticoidinduced glaucoma model. The results showed that, a better in vivo inhibitory effect of MTZ-PMs was achieved, compared to MTZ solution on glaucoma induction in experimental rabbits. Hence, these newly developed nano formulations have characteristics which are appropriate for ocular nanodelivery.
Secondly, in effort to develop improved nano-liposomal carriers for in vivo application on Zebrafish embryo models, in collaboration with Leiden University, we focused on preparation of new glicoliposome formulations, obtained by combining the advantages of synthetic sugar fatty acid esters and liposomes, in order to use this nano drug delivery system to target the Mannose receptor (mrc1) and to study their receptor specificity and potential for intracellular delivery in Liver sinusoidal endothelial cells (LSECs). We have successfully generated a LSECs-targeted glycol-liposomal drug delivery system with precise and in vivo confirmed specificity towards LSECs through interaction with the mrc1 receptor.
Another work carried out, was based on the formulation and characterization of a novel mixed/chimeric liposomal system. The bock copolymer methoxy polytylene glycol-co-poly (ddecalactone) (mPEGx-PDLy) was incorporated into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-diasteroyl-sn-glycero-3phosphocholine (DSPC) lipid bilayers. The chimeric liposomes were studied in regards with their physicochemical properties, their colloidal stability and their in vitro toxicity. As a result, depending on their thermodynamic, physicochemical and toxicity profiles, these chimeric polymer-grafted liposomes could be promising candidates for further in vitro and in vivo investigation for future nano drug delivery applications
Chitosans as new tools against biofilms formation on the surface of silicone urinary catheters
No full textUrinary catheters contamination by microorganisms is a major cause of hospital acquired infections and represents a limitation for long-term use. In this work, biofilms of Klebsiella pneumoniae and Escherichia coli clinical isolates were developed on urinary catheters for 48 and 72 h in artificial urine medium (AUM) with different molecular weight chitosans (AUM-CS solutions) at pH 5.0. The number of viable bacteria was determined by standard plate count agar while crystal violet (CV) staining was carried out to assess biomass production (optical density at 570 nm) in the mentioned conditions. Re-growth of each strain was also evaluated after 24 h re-incubation of the treated catheters. Significant decreases of log CFU/catheter and biomass production were observed for all the biofilms developed in AUM-CS compared with the controls in AUM. The percentages of biofilm removal were slightly higher for E. coli biofilms (up to 90.4%) than those of K. pneumoniae (89.7%); in most cases, the complete inhibition of bacterial re-growth on treated catheter pieces was observed. Contact time influenced chitosan efficacy rather than its molecular weight or the biofilms age. The results confirmed the potentiality of chitosans as a biomacromolecule tool to contrast biofilm formation and reduce bacterial re-growth on urinary catheters
Chitosans as new tools against biofilms formation on the surface of silicone urinary catheters
No full textUrinary catheters contamination by microorganisms is a major cause of hospital acquired infections and represents a limitation for long-term use. In this work, biofilms of Klebsiella pneumoniae and Escherichia coli clinical isolates were developed on urinary catheters for 48 and 72 h in artificial urine medium (AUM) with different molecular weight chitosans (AUM-CS solutions) at pH 5.0. The number of viable bacteria was determined by standard plate count agar while crystal violet (CV) staining was carried out to assess biomass production (optical density at 570 nm) in the mentioned conditions. Re-growth of each strain was also evaluated after 24 h re-incubation of the treated catheters. Significant decreases of log CFU/catheter and biomass production were observed for all the biofilms developed in AUM-CS compared with the controls in AUM. The percentages of biofilm removal were slightly higher for E. coli biofilms (up to 90.4%) than those of K. pneumoniae (89.7%); in most cases, the complete inhibition of bacterial re-growth on treated catheter pieces was observed. Contact time influenced chitosan efficacy rather than its molecular weight or the biofilms age. The results confirmed the potentiality of chitosans as a biomacromolecule tool to contrast biofilm formation and reduce bacterial re-growth on urinary catheters
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
Exploring optimized methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) crystalline cored micelles in anti-glaucoma pharmacotherapy
No full textMethoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) polymeric micelles (PMs) open a promising avenue through which ocular drug delivery with superior efficacy and tolerability can be potentially obtained. Methazolamide (MTZ) is an anti-glaucoma drug exhibiting poor corneal penetration, making it an ideal candidate for new polymeric micellar systems. MTZ-PMs were prepared using the thin film hydration procedure and optimized using a Design of Experiment (DoE) approach. In vitro drug release, thermal analyses and FT-IR characterization were also evaluated. MTT assay and histopathological assessment were carried out to verify ocular tolerability as well as Draize irritancy test. In vivo studies were conducted on rabbits to evaluate anti-glaucoma activity in a glucocorticoid-induced glaucoma model. The results showed successful entrapment of MTZ inside PMs matrix as reflected by the complete vanishing of drug melting peak in DSC thermogram and the possible formation of hydrogen bonding between MTZ and mPEG-PCL copolymer in FT-IR spectrum. The selected formula exhibited a particle size of 60 nm, entrapment efficiency of 93% and discrete spherical particles. Moreover, sustained release of MTZ, cellular and tissue biocompatibility and marked anti-glaucoma efficacy, as compared to MTZ solution, were realized. The combined results show that PMs could potentiate the therapeutic outcome of nanotechnology ocular drug delivery
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
