1,721,134 research outputs found
In situ composite ion-triggered gellan gum gel incorporating amino methacrylate copolymer microparticles: a therapeutic modality for buccal applicability
Full text linkThe aim of the current investigation is to delineate the buccal applicability of an in situ composite gel containing aceclofenac (AC) amino methacrylate copolymer microparticles (MPs), surmounting limitations of oral existing conventional therapy. AC Eudragit RL100 MPs were fabricated and statistically optimized using 2241 factorial design. Better buccal applicability and enhanced localization were achieved by combining the optimum MPs with in situ ion-activated gellan gum gel. The crosslinking and gelation of in situ gel were investigated by morphological and solid state characterizations. Suitability for buccal delivery and in vivo therapeutic efficacy in inflammation model of rats were also assessed. Results showed that the best performing formula displayed particle size (PS) of 51.00 μm and high entrapment efficiency (EE%) of 94.73%. MPs were successfully entrapped inside the gel network of the composite system. Gelation tendency, pH, shear-thinning properties and mucoadhesivity of the prepared in situ composite gel guaranteed its buccal suitability. Sustained AC release features and promising in vitro anti-arthritic response were also demonstrated. Moreover, consistent and prolonged in vivo anti-inflammatory effect was achieved, relative to standard AC. Taken together; this study proves the potential of in situ composite gel as an appropriate therapeutic proposal for AC buccal delivery
Star-shaped poly(oligoethylene glycol) copolymer-based gels: thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery
Full text linkThe aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37°C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in-situ gels should have promising application as nasal drug delivery systems
Gamma oryzanol loaded into micelle-core/chitosan-shell: from translational nephroprotective potential to emphasis on sirtuin-1 associated machineries
No full textGamma oryzanol (ORZ) is a nutraceutical that is poorly water soluble with poor intestinal absorption. In the current work, ORZ was nanoformulated into uncoated and chitosan coated micelles based on methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) and poly(ε-caprolactone)-b-methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (PCL-PEG-PCL) copolymers for augmenting ORZ oral delivery. The physicochemical properties, morphological study, in-vitro release and safety of the nanoplaforms were determined. Importantly, the nephroprotective competence of the nanoplaforms was analyzed against acute kidney injury (AKI) rat model and the sirtuin-1 associated machineries were assessed. The results revealed that the micelles exerted particle size (PS) from 97.9 to 117.8 nm that was markedly increased after chitosan coating. The reversal of zeta potential from negative to highly positive further confirmed efficient coating. In vitro release profiles demonstrated prolonged release pattern. The nanoforms conferred higher cell viability values than free ORZ on Vero cell line. The designed micelles displayed augmented nephroprotection compared to free ORZ with the supremacy of CS coated micelles over uncoated ones in restoring kidney parameters to normal levels. The attenuated AKI was fulfilled via the modulation of sirtuin-1 signaling pathways translated by restoring the histological features, increasing renal antioxidant states, renal autophagy and decreasing renal inflammation and renal apoptosis. These outcomes confirmed that surface modification with chitosan had a considerable leverage on micelles safety, release behavior and in vivo performance
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
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
Noscapine loaded biodegradable nanoparticles to treat breast cancer
No full textBreast cancer is the most common malignancy in women
worldwide. Therapeutic strategies currently involve a
combination of surgery, radiotherapy, immunotherapy,
hormone therapy and/or chemotherapy. The efficacy of a
chemotherapeutic formulation depends on its ability to
selectively target diseased tissue, overcome biological
barriers, and intelligently respond to the disease
environment to release cytotoxic agents. The development
of a controlled and targeted drug delivery system may result
in a more efficient and less harmful solution to overcome
the limitations associated with conventional chemotherapy
(Cho et al.). Recent studies have been focused on
developing nanoscale delivery vehicles capable of
controlling the release of chemotherapeutics directly inside
cancer cells. Micellar like nanoparticles (NPs) are produced
by the self-assembly of amphiphilic molecules into a
structure with a hydrophobic core and an hydrophilic outer
layer, with diameters generally less than 100 nm, allowing
them to extravasate through the tumor vessels fenestrations.
Moreover, their hydrophilic surfaces may shield them from
immediate recognition by reticuloendothelial system (RES)
leading to an increase in their circulation time. Many
micellar formulations are currently under clinical evaluation
for the treatment of cancer (e.g. doxorubicin, paclitaxel and
epirubicin). Therefore, the aim of this study was to
synthesize a series of linear-block and star-shaped
copolymers based on polyethylene glycol (PEG) and
poly(ε-caprolactone) (PCL), and to formulate noscapine
(NOS) loaded biodegradable NPs by the nanoprecipitation
technique. After characterization of these NPs, the best
formulae were tested for in-vitro release and cytotoxicity
using MCF-7 breast cancer cells. Pharmacokinetic
parameters and NPs in-vivo toxicity were also tested to
assess whether these NPs, would have high half-life in
addition to their low cytotoxicity, enhancing NOS passive
targeting to cancer cells. In addition, the selective release of
NOS as an alkaloid in the acidic medium was tested to
mimic what would happen in the vicinity of cancer tissues
and this would increase NOS safety and efficacy during its
use as anti-cancer agent
Artificial neural networks applied to biodegradable nanoparticles for Noscapine delivery
No full textBiopolymer based nanocarriers have been extensively studied as delivery systems for different therapeutics, due to their multiple favorable properties - e.g. small size, long circulation time, reduced opsonization, drug stability and controlled release [1-2].
In this study a series of biodegradable block copolymers based on polyethylene glycol (PEG) and poly lactide (PLA) were synthesized by ring opening polymerization (ROP).
Successively, biocompatible PLA nanoparticles loading Noscapine were prepared using the nanoprecipitation method and characterized for their size, drug entrapment efficiency and morphology.
Noscapine, an alkaloid derived from opium, has been widely used as antitussive agent for many years. However, more recently, it was discovered that it owns a tubulin binding activity. It affects the dynamics of microtubules resulting in arresting the metaphase of cell cycle which eventually leads to apoptosis of dividing cancer cells [3].
Artificial neural networks (ANNs) [4] were applied to predict particle size and Noscapine entrapment efficiency within the formed nanoparticles using different factors - i.e. copolymer molecular weight, ratio of polymer to drug and the number of blocks present in the copolymer backbone.
Using these networks it was found that the copolymer molecular weight has the greatest effect on the nanoparticle size distribution. On the other hand, polymer to drug ratio was found to be the most influential factor on drug entrapment efficiency.
ANNs may have a great impact on the design of PEG/PLA based copolymers, and they can be used to customize the formulations of nanoparticles that can fit required targets
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