1,720,968 research outputs found
Resveratrol-loaded nanocarrier for inner ear delivery
No full textPurpose: The aim of the work is to develop resveratrol-loaded nanocarriers (RES-NCs) for inner ear delivery and to evaluate in vitro toxicity on cochlear cell lines.
Materials and methods: RES-NCs are prepared by solvent-diffusion technique without surfactant. Resveratrol (RES), poly(D,L-lactide-co-glycolide) (PLGA) and poly(ε-caprolactone)–poly(ethylene glycol) diblock (PCL-PEG) are mixed in different ratios, dissolved in acetone and added dropwise to aqueous phase under constant stirring (acetone/water ratio 1/10). RES-NCs are washed and freeze-dried. Box-Behnken design (BBD) is used to study influence of RES-NCs composition on Z-size, PDI, Zeta-potential, drug encapsulation efficiency (EE%) and ratio between RES-NCs Z-size before and after freeze-drying (Sf/Si). In order to increase RES-NC stability during freeze-drying, lactose, mannitol, sucrose and trehalose are tested at different concentrations (1%, 5%, 10%, 15%, 20%w/v). Finally, MTS and LDH assays are carried out to check RES and Blank NCs toxicity after 24h incubation on two different cell lines: an organ of Corti model (HEI-OC1) and a stria vascularis one (SVK-1).
Results: BBD model is validated since all experimental responses fit with predicted values. Checkpoint analyses (bias NMT 10%) and Montecarlo simulation (response defect values NMT 10%) show good robustness in model capability to predict RES-NCs properties. The optimal formulation (desirability: 0.86), made of 7.4mg of RES, 3mg of PLGA and 5.3mg of PCL-PEG, correspond to Z-size of 136.2nm, PDI of 0.127, Z- potential of -26.80mV, EE% of 100.09% and Sf/Si of 3.30. All cryoprotectants increase RES-NCs stability during freeze-drying, disaccharides are more effective than mannitol. However, only trehalose in concentration higher than 15%w/v maintains Z-size and PDI in model space. In vitro toxicity studies show that RES can decrease cell viability only at concentration higher than 500μM, whereas blank NCs are toxic on HEI-OC1 in concentration more than 800μg/mL.
Conclusion: RES-NCs are successfully prepared by emulsion-diffusion technique and optimized by BBD. Moreover, threalose at 15%w/v guarantees RES-NCs stability during freeze-drying process.
Finally, in vitro studies show that RES and NCs are not toxic for cochlear cell lines in concentration lower than 500μg/mL and 800μg/mL respectively
Label-Free Ferrocene-Loaded Nanocarrier Engineering for In Vivo Cochlear Drug Delivery and Imaging
No full textIt is hypothesized that ferrocene (FC)-loaded nanocarriers (FC-NCs) are safe label-free contrast agents for cochlear biodistribution study by transmission electron microscopy (TEM). To test this hypothesis, after engineering, the poly(epsilon-caprolactone)/polyglycolide NCs are tested for stability with various types and ratios of sugar cryoprotectants during freeze-drying. Their physicochemical properties are characterized by UV-visible spectroscopy, dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM/EDS). The biodistribution of the FC-NCs in the cochlear tissue after intratympanic injection in guinea pigs is visualized by TEM. Auditory brainstem responses are measured before and after 4-day treatments. These FC-NCs have 153.4 ± 8.7 nm, 85.5 ± 11.2%, and -22.1 ± 1.1 mV as mean diameters, percent drug association efficiency, and zeta potential, respectively (n = 3). The incorporation of FC into the NCs is confirmed by Fourier transform infrared spectroscopy and SEM/EDS spectra. Lactose (3:1 ratio, v/v) is the most effective stabilizer after a 12-day study. The administered NCs are visible by TEM in the scala media cells of the cochlea. Based on auditory brainstem response data, FC-NCs do not adversely affect hearing. Considering the electrondense, radioactive, and magnetic properties of iron inside FC, FC-NCs are promising nanotemplate for future inner ear theranostics
Optimization of resveratrol nanoformulation and evaluation of its cytotoxicity on cochlear derived cells
No full textPurpose: The aim of the work is to develop resveratrol (RES)-loaded nanocarriers (NCs) intended for cochlear drug delivery. Furthermore, in vitro toxicity of the synthesized NCs is evaluated in cochlear cell lines.
Methods: RES-NCs are prepared by solvent-diffusion technique without surfactant. RES, PLGA and PCL-PEG di-block are mixed in different ratios, dissolved in acetone and added dropwise to aqueous phase under constant stirring (acetone/water ratio 1/20). RES-NCs are washed twice and freeze-dried. Box-Behnken design (BBD) is used to study the influence of formulation variables on Z-size, Polydispersity index (PDI), Zeta-potential, drug encapsulation efficiency (EE%) and ratio between Z-size before and after freeze-drying (S f/Si). To increase RES-NC stability during freeze-drying, lactose, mannitol, sucrose and trehalose are tested at different concentrations (1%, 5%, 10%, 15%, 20%w/v). Finally, MTS and LDH assays are carried out to check RES and Blank NCs in vitro toxicity after 24h incubation in an organ of Corti (HEI-OC1) and a stria vascularis
(SVK-1) cell lines.
Results: BBD model is validated since all experimental responses fit with predicted values. Checkpoint analyses (bias 500μM) and blank NCs (>800μg/mL) affect the cell viability.
Conclusion: RES-NCs are successfully synthesized and optimized by BBD. In addition, in vitro studies show that RES (<500μM) and blank NCs (< 800μg/mL) are non-toxic for HEI-OC1 and SVK-1 cells
Ferrocene-loaded nanocarrier as probe for cochlear biodistribution study
No full textPurpose: The fate of drug nanocarriers (NCs) in the inner ear remains elusive. The aim of the work is to develop ferrocene (FER)-loaded NCs to elucidate the cochlear biodistribution of such NCs.
Methods: FER-NCs were prepared by surfactant free solvent-diffusion technique using a mixture of PLGA/PCL-PEG (ratios 1/1, 1/2) dissolved in acetone. FER-NCs were washed and freeze-dried. TEM analyses were carried out to study the FER-NC morphology. Lactose, mannitol, sucrose were tested at different cryoprotectant/nanocarrier ratios (0/1, 1/1, 3/1, 5/1) to stabilize FER-NCs during freeze-drying. The stability of the FER-NCs was checked by measuring particle size and zeta potential (ZP) immediately after water dispersion and after 12 days. FER-NCs were placed in the round window (RW) niche of the middle ear in guinea pigs. After 48 hours, the animals were sacrificed, the cochlea isolated and prepared for TEM.
Results: The Ferrocene-loaded NCs had a mean diameter of 201.2±57.7, PDI of 0.328±0.074 and ZP of -20.2±4.8mV. PLGA/PCLPEG NCs of 1/2 allowed higher EE% (85.50±11.15) than ones made with 1/1 ratio (42.93±3.65). The FER-NCs appeared spherical with smooth surface. All cryoprotectants increased RES-NCs stability during the freeze-drying process. However, lactose, especially when used in 3/1 ratio, was more effective than other ones after dispersion and during 12-day stability studies. FER-NCs crossed the RW membrane and were found adjacent or in the cells lining the scala tympani of the cochlea. Hearing was normal after RW placement of NCs.
Conclusion: FER-NCs were successfully prepared by emulsion-diffusion technique and the 1/2 PLGA/PLC-PEG ratio was selected in term of best encapsulation efficiency. Moreover, lactose (3/1 cryoprotectant/NCs ratio) guaranteed FER-NCs stability during freeze-drying process and maintained FER-NCs stable in suspension for at least 12 days. When placed into the RW niche, FER-NCs enter the cochlea and do not appear to cause hearing loss
Resveratrol-loaded nanocarriers: formulation, optimization, characterization and in vitro toxicity on cochlear cells
No full textThe present work aimed to investigate the suitability of polymeric nanoparticles (NPs) loaded with resveratrol (RES) for drug delivery to cochlear cells. RES-loaded NPs were prepared by a solvent-diffusion method without surfactant. The Box–Behnken design was used to study the effect of the formulation variables on the particle mean diameter (PMD), polydispersity index (PDI), zeta-potential (ζ), percent drug encapsulation efficiency (EE%), and ratio between NP size before and after freeze-drying (Sf/Si). The physicochemical stability of the RES-loaded NPs during freeze-drying was investigated using four well-known cryoprotectants (i.e., lactose, mannitol, sucrose, and trehalose) at different concentrations. The RES-loaded NPs were also characterized by powder X-ray diffraction (PXRD) and in vitro drug release studies. Finally, the in vitro toxicity of the synthesized NPs was evaluated on two cochlear cell lines: HEI-OC1 and SVK-1 cells. The optimal formulation (desirability: 0.86) had 135.5 ± 37.3 nm as PMD, 0.126 ± 0.080 as PDI, −26.84 ± 3.31 mV as ζ, 99.83 ± 17.59% as EE%, and 3.30 ± 0.92 as Sf/Si ratio. The PMD and PDI of the RES-loaded NPs were maintained within the model space only when trehalose was used at concentrations higher than 15% (w/v). Results from the in vitro cytotoxicity studies showed that blank NPs did not alter the viability of both cells lines, except for concentrations higher than 600 μg/mL. However, the cell viability was significantly decreased at high concentrations of native RES (>50 μM, p < 0.05) in both cell lines. Overall, the results suggested that the RES-loaded polymeric NPs could be a suitable template for cochlea antioxidant delivery and otoproctection
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
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
- …
