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Journal of Translational Medicine May 2023
Topics: Humans; COVID-19; Reducing Agents; COVID-19 Drug Treatment; Disease Outbreaks; Dexamethasone
PubMed: 37237409
DOI: 10.1186/s12967-023-04186-4 -
Acta Paediatrica Scandinavica.... 1989Sixteen chronically ventilator-dependent newborns with BPD were treated with one or more cycles of dexamethasone (0.5 mg/kg/day). In 11 cases extubation was possible...
Sixteen chronically ventilator-dependent newborns with BPD were treated with one or more cycles of dexamethasone (0.5 mg/kg/day). In 11 cases extubation was possible during the therapy period. Ventilatory parameters were lowered in 3 other newborns. FIO2, respiratory rate, PIP, and PEEP, assessed before and after dexamethasone administration, decreased in a statistically significant way. Our data confirm the utility of dexamethasone in the extubation in chronically ventilated infants with BPD.
Topics: Bronchopulmonary Dysplasia; Dexamethasone; Humans; Infant, Newborn; Length of Stay; Oxygen Inhalation Therapy; Respiration, Artificial; Respiratory Function Tests
PubMed: 2642245
DOI: 10.1111/j.1651-2227.1989.tb11290.x -
Colloids and Surfaces. B, Biointerfaces Mar 2019Combining a low-molecular-weight hydrogel (LMWH) with a polymeric hydrogel overcomes the disadvantages of the LMWH (e.g., its low mechanical property) and is associated...
Combining a low-molecular-weight hydrogel (LMWH) with a polymeric hydrogel overcomes the disadvantages of the LMWH (e.g., its low mechanical property) and is associated with the enhancement of materials performance, which is useful in a variety of biomedical applications. In the present work, a hybrid hydrogel that combines dexamethasone sodium phosphate (Dexp) and a polysaccharide (alginate) was explored via a calcium ion coordination strategy. With the addition of Ca to an aqueous solution of Dexp/alginate, the Ca/Dexp/alginate hybrid hydrogel formed spontaneously. The formed Ca/Dexp/alginate hybrid hydrogels were thoroughly characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (XRD). An in vitro drug release study indicated that the formed Ca/Dexp/alginate hybrid hydrogel provided a slower drug release rate than did the Ca/Dexp hydrogel, and the drug release behaviour could be finely tailored by the change of Ca concentration. More importantly, the subcutaneous injection of the Ca/Dexp/alginate hybrid hydrogel significantly extended the in vivo retention of the hydrogel in situ compared to that of the Ca/Dexp hydrogel. The in vivo pharmacokinetic analysis indicated that the Ca/Dexp/alginate hybrid hydrogel could greatly extend drug release in vivo and significantly improve drug bioavailability compared to the Ca/Dexp hydrogel. As such, the formed Ca/Dexp/alginate hybrid hydrogel combined the greater resilience of an alginate network with the long in vivo duration of a low-molecular-weight hydrogel (Ca/Dexp hydrogel) and remarkably enhanced drug bioavailability, which might open an avenue for the design of self-assembling steroidal drug-polysaccharide hybrid hydrogels for drug delivery applications.
Topics: Alginates; Animals; Calcium Chloride; Delayed-Action Preparations; Dexamethasone; Drug Carriers; Drug Liberation; Hydrogels; Injections, Subcutaneous; Kinetics; Mice; Mice, Inbred BALB C
PubMed: 30580147
DOI: 10.1016/j.colsurfb.2018.11.083 -
Klinische Monatsblatter Fur... Mar 2020Radiation Retinopathy is a progressive chronic disease triggered by ionising radiation and is characterised by vascular endothelial damage that can lead to macular...
Radiation Retinopathy is a progressive chronic disease triggered by ionising radiation and is characterised by vascular endothelial damage that can lead to macular edema, optic disc edema and proliferative retinopathy. We discuss a case of a patient with radiation retinopathy and optic disc edema who we treated with a combination of intravitreal bevacizumab and dexamethasone. After 3 injections of bevacizumab, and one of dexamethasone, the patient experienced a resolution of optic disc edema and a marked increase of his visual acuity and remained stable throughout the follow-up period.
Topics: Angiogenesis Inhibitors; Bevacizumab; Dexamethasone; Diabetic Retinopathy; Glucocorticoids; Humans; Intravitreal Injections; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A
PubMed: 30477040
DOI: 10.1055/a-0735-9865 -
Ecotoxicology and Environmental Safety Apr 2023Dexamethasone (DEX) is a synthetic glucocorticoid widely found in a variety of aquatic environments and has potential adverse effects on aquatic organisms. This study...
Dexamethasone (DEX) is a synthetic glucocorticoid widely found in a variety of aquatic environments and has potential adverse effects on aquatic organisms. This study was to assess the toxic effects of exposure to different concentrations (0, 5 and 50 μg/L) of DEX for 60 days on adult male mosquitofish (Gambusia affinis). Morphological analyses of skeleton and anal fin, histological effects of testes and livers, and transcriptional expression levels of genes related to reproductive and immune system were determined. The results showed that exposure to DEX significantly increased 14L and 14D values of hemal spines, which suggested DEX could affect skeleton development and result in more masculine characteristics in male fish. In addition, the damage to testis and liver tissue was observed after DEX treatment. It also enhanced mRNA expression of Erβ gene in the brain and Hsd11b1 gene in the testis. The findings of this study reveal physiological and transcriptional effects of DEX on male mosquitofish.
Topics: Animals; Male; Reproduction; Cyprinodontiformes; Dexamethasone; Water Pollutants, Chemical
PubMed: 36870310
DOI: 10.1016/j.ecoenv.2023.114722 -
The Journal of Pharmacy and Pharmacology Aug 2016Ocular diseases affecting retina, such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the major causes of blindness, and their...
OBJECTIVE
Ocular diseases affecting retina, such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the major causes of blindness, and their treatment is still a challenge due to the special structure of the eye. The purpose of this study was to prepare a sustained release DEX conjugate formulation with enhanced ocular permeation using poly(amidoamine) (PAMAM) dendrimers and to evaluate the effects of conjugation on DEX release and ocular residence time.
METHODS
PAMAM G3.5 and PAMAM G4.5 dendrimers were used to prepare DEX conjugates, and conjugation was confirmed using (1) H-NMR. Formulations were evaluated in terms of drug release in the presence of ocular enzymes and cytotoxicity on ARPE19 cell lines. Fluorotron analysis was performed and ocular pharmacokinetic properties of DEX-PAMAM conjugates were studied in Sprague Dawley rats following intravitreal and subconjunctival applications.
KEY FINDINGS
The results indicated that DEX-PAMAM conjugates were able to enhance ocular permeability and ocular tissue levels of DEX following subconjunctival injection, and results were encouraging when compared to the literature that has reported DEX getting cleared from vitreous in 3 h.
CONCLUSION
Current studies are focused on formulation improvement to enhance hydrolysis and clearance time.
Topics: Animals; Chemistry, Pharmaceutical; Dendrimers; Dexamethasone; Drug Administration Routes; Drug Carriers; Drug Delivery Systems; Drug Liberation; Male; Permeability; Rats, Sprague-Dawley; Retina; Retinal Diseases
PubMed: 27283886
DOI: 10.1111/jphp.12587 -
Clinical Lymphoma, Myeloma & Leukemia Nov 2020Glucocorticoids, particularly dexamethasone, are often used in combination with novel agents in multiple myeloma. This study compared the safety, rate, and extent of... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparative Safety, Bioavailability, and Pharmacokinetics of Oral Dexamethasone, 4-mg and 20-mg Tablets, in Healthy Volunteers Under Fasting and Fed Conditions: A Randomized Open-label, 3-way Crossover Study.
BACKGROUND
Glucocorticoids, particularly dexamethasone, are often used in combination with novel agents in multiple myeloma. This study compared the safety, rate, and extent of absorption of a single dose of an orally administered 20-mg dexamethasone tablet to five 4-mg tablets (total, 20 mg).
PATIENTS AND METHODS
This was a single-center, open-label, randomized, 3-way crossover comparative study. Thirty-six volunteers received at least 1 dose of either a single 20-mg dexamethasone tablet, under fasting or fed conditions, or five 4-mg dexamethasone tablets (total, 20 mg). Blood samples were collected before study drug administration and at 21 time points for up to 36 hours after drug administration.
RESULTS
Mean area under the concentration-time curve from time zero to the time of last non-zero concentration (AUC), mean area under the concentration-time curve from time zero to infinity (extrapolated) (AUC), and maximum observed concentration (C) were 1314.38 ng × h/mL, 1329.24 ng × h/mL, and 257.22 ng/mL, respectively for fasting test formulation (single dexamethasone 20-mg tablet), 1339.74 ng × h/mL, 1358.07 ng × h/mL, and 194.56 ng/mL, respectively, for the fed test formulation (single dexamethasone 20-mg tablet), and 1325.12 ng × h/mL, 1342.12 ng × h/mL, and 244.12 ng/mL, respectively, for the reference formulation (5 dexamethasone 4-mg tablets). The median time of observed C was 0.997 hours for the fasting and 2.502 hours for the fed test formulation, compared with 1.495 hours for the reference. Mean plasma elimination half-lives (t) were 4.0 hours (test fasting), 4.03 hours (test fed), and 3.96 hours (reference). The point estimates and 90% confidence intervals (CIs) for AUC, AUC, and C were 99.37% (90% CI, 95.65%-103.24%), 99.24% (90% CI, 95.47%-103.16%), and 106.28% (90% CI, 97.69%-115.62%), respectively, satisfying the bioequivalence criteria of the United States Food and Drug Administration guidelines.
CONCLUSION
The 2 formulations were well-tolerated, and one 20-mg tablet or five 4-mg tablets of dexamethasone are bioequivalent under fasting conditions and thus may be prescribed interchangeably.
Topics: Administration, Oral; Adult; Cross-Over Studies; Dexamethasone; Fasting; Female; Healthy Volunteers; Humans; Male; Middle Aged; Young Adult
PubMed: 32900662
DOI: 10.1016/j.clml.2020.06.022 -
Biotechnology and Applied Biochemistry Apr 2001Human erythrocytes from ten patients with chronic obstructive pulmonary disease (COPD) were loaded with increasing amounts of dexamethasone 21-phosphate and were... (Clinical Trial)
Clinical Trial
Human erythrocytes from ten patients with chronic obstructive pulmonary disease (COPD) were loaded with increasing amounts of dexamethasone 21-phosphate and were re-infused into the original donors. Drug-loaded erythrocytes acted as circulating bioreactors, converting the non-diffusible dexamethasone 21-phosphate into the diffusible dexamethasone. Pharmacokinetic analyses on these patients showed that a single administration of drug-loaded erythrocytes was able to maintain detectable dexamethasone concentrations in blood for up to seven days. This continuous release of dexamethasone was paralleled by the suspension of beta2-agonist and oral corticosteroid treatments by all of the patients. Thus dexamethasone 21-phosphate-loaded erythrocytes are safe carriers for corticosteroid analogues and are a useful alternative to frequent oral or inhaled drugs in elderly patients with COPD.
Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Chronic Disease; Dexamethasone; Drug Administration Schedule; Drug Carriers; Drug Delivery Systems; Erythrocytes; Humans; Lung Diseases, Obstructive; Middle Aged
PubMed: 11277860
DOI: 10.1042/ba20000087 -
ACS Applied Materials & Interfaces Jul 2021Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment...
Osteoarthritis (OA) is treated with the intra-articular injection of steroids such as dexamethasone (DEX) to provide short-term pain management. However, DEX treatment suffers from rapid joint clearance. Here, 20 × 10 μm, shape-defined poly(d,l-lactide-co-glycolide)acid microPlates (μPLs) are created and intra-articularly deposited for the sustained release of DEX. Under confined conditions, DEX release is projected to persist for several months, with only ∼20% released in the first month. In a highly rigorous murine knee overload injury model (post-traumatic osteoarthritis), a single intra-articular injection of Cy5-μPLs is detected in the cartilage surface, infrapatellar fat pad/synovium, joint capsule, and posterior joint space up to 30 days. One intra-articular injection of DEX-μPL (1 mg kg) decreased the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and matrix metalloproteinase (MMP)-13 by approximately half compared to free DEX at 4 weeks post-treatment. DEX-μPL also reduced load-induced histological changes in the articular cartilage and synovial tissues relative to saline or free DEX. In sum, the μPLs provide sustained drug release along with the capability to precisely control particle geometry and mechanical properties, yielding long-lasting benefits in overload-induced OA. This work motivates further study and development of particles that provide combined pharmacological and mechanical benefits.
Topics: Animals; Biomarkers; Cartilage, Articular; Delayed-Action Preparations; Dexamethasone; Drug Carriers; Gene Expression Regulation; Injections, Intra-Articular; Mice; Osteoarthritis; Polylactic Acid-Polyglycolic Acid Copolymer; Stress, Mechanical
PubMed: 34197081
DOI: 10.1021/acsami.1c02082 -
Nanomedicine : Nanotechnology, Biology,... Aug 2014The encapsulation of drugs into liposomes aims to enhance their efficacy and reduce their toxicity. Corticosteroid-loaded liposomes are currently being evaluated in...
UNLABELLED
The encapsulation of drugs into liposomes aims to enhance their efficacy and reduce their toxicity. Corticosteroid-loaded liposomes are currently being evaluated in patients suffering from rheumatoid arthritis, atherosclerosis, colitis, and cancer. Here, using several different fluorophore-labeled formulations, we comprehensively studied the impact of liposome encapsulation of the prototypic corticosteroid dexamethasone on various primary human cells in vitro. Liposomal dexamethasone targeted several primary cell types in a dose and time-dependent manner, but specifically reduced cytotoxicity against human fibroblasts and macrophages in comparison to the solute drug. Furthermore, macrophage maturation and polarization markers were altered. Interestingly, liposomal dexamethasone induced proinflammatory cytokine secretion (specifically TNF, IL1β, IL6) in unstimulated cells, but reduced this response under inflammatory conditions. Monocyte and macrophage migration was significantly inhibited by dexamethasone-loaded liposomes. The findings indicate that the encapsulation of dexamethasone into liposomes modulates their cellular mechanism of action, and provides important indications for follow-up in vivo investigations.
FROM THE CLINICAL EDITOR
This study investigates mechanism of action of liposomal dexamethason in the treatment of inflammatory conditions. It is concluded that liposomal dexamethasone actually induces proinflammatory cytokine secretion in unstimulated cells, but reduces the same response under inflammatory conditions. Monocyte and macrophage migration was also inhibited. The findings indicate that liposomal dexamethasone may have different mechanisms of action than its native counterpart.
Topics: Anti-Inflammatory Agents; Cell Movement; Cells, Cultured; Cytokines; Dexamethasone; Humans; Liposomes; Macrophages
PubMed: 24607939
DOI: 10.1016/j.nano.2014.02.011