scholarly journals Dexamethasone for Inner Ear Therapy: Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1896
Author(s):  
Ziwen Gao ◽  
Jana Schwieger ◽  
Farnaz Matin-Mann ◽  
Peter Behrens ◽  
Thomas Lenarz ◽  
...  

Dexamethasone is widely used in preclinical studies and clinical trials to treat inner ear disorders. The results of those studies vary widely, maybe due to the different dexamethasone formulations used. Laboratory (lab) and medical grade (med) dexamethasone (DEX, C22H29FO5) and dexamethasone dihydrogen phosphate-disodium (DPS, C22H28FNa2O8P) were investigated for biocompatibility and bio-efficacy in vitro. The biocompatibility of each dexamethasone formulation in concentrations from 0.03 to 10,000 µM was evaluated using an MTT assay. The concentrations resulting in the highest cell viability were selected to perform a bio-efficiency test using a TNFα-reduction assay. All dexamethasone formulations up to 900 µM are biocompatible in vitro. DPS-lab becomes toxic at 1000 µM and DPS-med at 2000 µM, while DEX-lab and DEX-med become toxic at 4000 µM. Bio-efficacy was evaluated for DEX-lab and DPS-med at 300 µM, for DEX-med at 60 µM, and DPS-lab at 150 µM, resulting in significantly reduced expression of TNFα, with DPS-lab having the highest effect. Different dexamethasone formulations need to be applied in different concentration ranges to be biocompatible. The concentration to be applied in future studies should carefully be chosen based on the respective dexamethasone form, application route and duration to ensure biocompatibility and bio-efficacy.

2021 ◽  
Vol 11 ◽  
Author(s):  
Osmel Companioni ◽  
Cristina Mir ◽  
Yoelsis Garcia-Mayea ◽  
Matilde E. LLeonart

Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. Sphingolipids are modified in multiple cancers and are responsible for tumor proliferation, progression, and metastasis. Several inhibitors or activators of sphingolipid signaling, such as fenretinide, safingol, ABC294640, ceramide nanoliposomes (CNLs), SKI-II, α-galactosylceramide, fingolimod, and sonepcizumab, have been described. The objective of this review was to analyze the results from preclinical and clinical trials of these drugs for the treatment of cancer. Sphingolipid-targeting drugs have been tested alone or in combination with chemotherapy, exhibiting antitumor activity alone and in synergism with chemotherapy in vitro and in vivo. As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. Aslthough all these drugs have produced good results in preclinical studies of multiple cancers, the outcomes of clinical trials have not been similar. The most effective drugs are fenretinide and α-galactosylceramide (α-GalCer). In contrast, minor adverse effects restricted to a few subjects and hepatic toxicity have been observed in clinical trials of ABC294640 and safingol, respectively. In the case of CNLs, SKI-II, fingolimod and sonepcizumab there are some limitations and absence of enough clinical studies to demonstrate a benefit. The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review.


Nanomedicine ◽  
2021 ◽  
Author(s):  
Milad Ghorbani ◽  
Zhila Izadi ◽  
Samira Jafari ◽  
Eudald Casals ◽  
Foroogh Rezaei ◽  
...  

The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages.


2013 ◽  
Vol 37 (4) ◽  
pp. 403-406 ◽  
Author(s):  
S Tamilselvam ◽  
MJ Divyanand ◽  
P Neelakantan

Objective: This aim of this study was at compare the fibroblast cytotoxicicty of four restorative materials - a conventional glass ionomer cement (GC Fuji Type II GIC), a ceramic reinforced glass ionomer cement (Amalgomer), a giomer (Beautifil II) and a resin composite (Filtek Z350) at three different time periods (24, 48 and 72 hours). Method: The succinyl dehydrogenase (MTT) assay was employed. Cylindrical specimens of each material (n=15) were prepared and stored in Dulbecco's modified Eagle medium, following which L929 fibroblasts were cultured in 96 well plates. After 24 hours of incubation, the MTT assay was performed to detect the cell viability. The method was repeated after 48 and 72 hours. The impact of materials and exposure times on cytotoxicity of fibroblasts was statistically analyzed using two way ANOVA (P=0.05). Results: Both time and material had an impact on cell viability, with giomer demonstrating the maximum cell viability at all time periods. The cell viability in the giomer group was significantly different from all other materials at 24 and 72 hours (P<0.05), while at 48 hours giomer was significantly different only with resin composite (P<0.05). Conclusions: Giomers showed better biocompatibility than conventional and ceramic reinforced glass ionomer cements and, resin composite. Ceramic reinforced glass ionomer demonstrated superior biocompatibility compared to conventional glass ionomer.


2017 ◽  
Vol 12 (2) ◽  
pp. 8 ◽  
Author(s):  
Ashutosh Bahuguna ◽  
Imran Khan ◽  
Vivek K. Bajpai ◽  
Sun Chul Kang

<p>Quantification of cell viability and proliferation form the fundamental for numerous <em>in vitro</em> assays in response to external factors. An MTT assay is a colorimetric assay based on assessing the cell metabolic activity. A549 Lung adenocarcinoma cell line was used to see the cytotoxic potential of a new drug for initial screening of apoptosis or necrosis. The biochemical mechanism behind the MTT assay involves NAD(P)H-dependent cellular oxidoreductase enzyme that converts the yellow tetrazolium MTT [3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide] into insoluble (E,Z)-5-(4,5-dimethylthiazol-2-yl)-1,3-diphenylformazan (formazan). The formed formazan can be dissolved with dimethyl sulfoxide (DMSO) to give a purple color with characteristic absorption at 540 nm. Intensity of purple color is directly proportional to the cell number and thus indicating the cell viability.</p><p><strong>Video Clip of Methodology:</strong> 3 min 56 sec  <a href="https://www.youtube.com//v/eqFxzDVunt8">Full screen</a>   <a href="https://www.youtube.com/watch?v=eqFxzDVunt8">If Failed</a></p>


2017 ◽  
Vol 13 (50) ◽  
pp. 365 ◽  
Author(s):  
Dominik Lenz ◽  
LucianaS Gasparini ◽  
NayanaD Macedo ◽  
ElisângelaF Pimentel ◽  
Marcio Fronza ◽  
...  
Keyword(s):  

Author(s):  
Murilo Batista Abud ◽  
Ricardo Noguera Louzada ◽  
David Leonardo Cruvinel Isaac ◽  
Leonardo Gomes Souza ◽  
Ricardo Gomes dos Reis ◽  
...  

Abstract Background To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). Methods In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit’s eyes following injection. Results Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p < 0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p = 1.0). The difference between groups 1 to 7 and group 8 (p < 0.0001) was significant. Histopathological changes were not found in any group. No activation of Müller cells was detected. Conclusion A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.


Nanomaterials ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1412 ◽  
Author(s):  
Luis Eduardo Genaro ◽  
Giovana Anovazzi ◽  
Josimeri Hebling ◽  
Angela Cristina Cilense Zuanon

Resin-modified glass ionomer cement (RMGIC) has important properties. However, like other restorative materials, it has limitations such as decreased biocompatibility. The incorporation of nanoparticles (NP) in the RMGIC resulted in improvements in some of its properties. The aim of this study was to evaluate the physical-biological properties of RMGIC with the addition of nanohydroxyapatite (HANP). Material and Methods: Vitremer RMGIC was used, incorporating HANP by amalgamator, vortex and manual techniques, totaling ten experimental groups. The distribution and dispersion of the HANP were evaluated qualitatively by field emission scanning electron microscope (SEM-FEG). The evaluation of image porosity (SEM-FEG) with the help of imageJ. Cell viability 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazoline bromide (MTT) and cell morphology analyses were performed on MDPC-23 odontoblastoid cells at 24 and 72 h. Results: It was possible to observe good dispersion and distribution of HANP in the samples in all experimental groups. The incorporation of 5% HANP into the vortex stirred RMGIC resulted in fewer pores. The increase in the concentration of HANP was directly proportional to the decrease in cytotoxicity. Conclusions: It is concluded that the use of a vortex with the incorporation of 5% HANP is the most appropriate mixing technique when considering the smallest number of pores inside the material. A higher concentration of HANP resulted in better cell viability, suggesting that this association is promising for future studies of new restorative materials.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Richard Heyes ◽  
Andrew Iarocci ◽  
Yourka Tchoukalova ◽  
David G. Lott

This review aims to summarize contemporary evidence of the in vitro and in vivo immunomodulatory effects of mesenchymal stem cells (MSCs) in promoting vascularized composite allotransplant (VCA) tolerance. An extensive literature review was performed to identify pertinent articles of merit. Prospective preclinical trials in mammal subjects receiving VCA (or skin allograft) with administration of MSCs were reviewed. Prospective clinical trials with intravascular delivery of MSCs in human populations undergoing solid organ transplant were also identified and reviewed. Sixteen preclinical studies are included. Eleven studies compared MSC monotherapy to no therapy; of these, ten reported improved graft survival, which was statistically significantly prolonged in eight. Eight studies analyzed allograft survival with MSC therapy as an adjunct to proven immunosuppressive regimens. In these studies, daily immunosuppression was transiently delivered and then stopped. In all studies, treatment-free graft survival was statistically significantly prolonged in animals that received MSC therapy. MSCs have been safely administered clinically and their use in renal transplant clinical trials provides evidence that they improve allograft transplant tolerance in clinical practice. There is potential for MSC induction therapy to overcome many of the obstacles to widespread VCA in clinical practice. Preclinical studies are needed before MSC-induced VCA tolerance becomes a clinical reality.


2020 ◽  
Vol 5 (1) ◽  
pp. 6
Author(s):  
Robiansyah Robiansyah ◽  
Debby Saputera ◽  
Rahmad Arifin

Background: Denture stomatitis is inflammation of the oral mucosa which supporting the denture that caused by Candida albicans. Candida albicans contamination can be prevented by immersing dentures into denture cleanser solution. One of the alternative ingredients that can be used as denture cleanser is small white ginger rhizome (Zingiber officinale var. Amarum). Objective: This study aimed to analyze whether small white ginger extract (Zingiber officinale var. Amarum) was toxic to BHK-21 fibroblast cells using the MTT assay method. Method: This study was conducted in 7 groups. Five groups consisted of extracts of 30%, 40%, 50%, 60%, 70% and 2 control groups comprised of media control and cell control. Absorbance was read using ELISA reader and cell viability was calculated. Results: The percentage of living cells of all groups of small white ginger extract treatment was 100%. The parametric analysis of One Way Annova showed p = 0.498 (p> 0.05) Conclusion: Small white ginger extract (Zingiber officinale var. Amarum) is not toxic to BHK-21 fibroblast cells using the MTT Assay method because cell viability of all concentration groups is  ≥ 60%.


2006 ◽  
Vol 309-311 ◽  
pp. 395-398
Author(s):  
A.W. Haryadi ◽  
Chang Kuk You ◽  
Shin Yoon Kim ◽  
Eui Kyun Park ◽  
Suk Young Kim

Grit-blasting using bioactive HA and biodegradable CMP followed by acid etching was done. The apatite formation of prepared Ti samples was evaluated by immersion in R-SBF. And cell viability, proliferation, and differentiation were conducted using MTT assay and ALP staining. In RSBF immersion tests, non-etched HA-blasted samples showed the faster apatite-like formation than other samples. Acid etched and non-etched HA-blasted samples showed better cell viability and proliferation compared to CMP-blasted samples after 1 and 3 days. And the cell differentiation of non-etched HA-blasted samples was better compared to etched ones, and etched and non-etched CMP-blasted samples.


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