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Journal of Drug Targeting Sep 2022Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory...
Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory activity. The EDLs were prepared using lipids extracted from erythrocyte membranes, which are rich in omega-3 fatty acids with several health benefits. Diclofenac, a widely used anti-inflammatory drug, was incorporated into EDLs in relevant therapeutic concentrations. The EDLs were also functionalised with folic acid to allow their active targeting of M1 macrophages, which are key players in inflammatory processes. In the presence of lipopolysaccharide (LPS)-stimulated macrophages, empty EDLs and EDLs incorporating diclofenac were able to reduce the levels of important pro-inflammatory cytokines, namely interleukin-6 (IL-6; ≈85% and 77%, respectively) and tumour necrosis factor-alpha (TNF-α; ≈64% and 72%, respectively). Strikingly, cytocompatible concentrations of EDLs presented similar effects to dexamethasone, a potent anti-inflammatory drug, in reducing IL-6 and TNF-α concentrations, demonstrating the EDLs potential to be used as bioactive carriers in the treatment of inflammatory diseases.
Topics: Anti-Inflammatory Agents; Cytokines; Diclofenac; Erythrocytes; Humans; Inflammation; Interleukin-6; Liposomes; Tumor Necrosis Factor-alpha
PubMed: 35414285
DOI: 10.1080/1061186X.2022.2066107 -
Small (Weinheim An Der Bergstrasse,... Jun 2024Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional...
Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti-inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA-DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA-DCF) as the MNs tips and then modifying the surface of MNs tips with a self-adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti-inflammatory cell tests and therapeutic animal experiments, down-regulating the expression levels of pro-inflammatory factors and alleviating articular cartilage destruction.
Topics: Osteoarthritis; Animals; Drug Delivery Systems; Needles; Diclofenac; Hyaluronic Acid; Lubrication; Humans; Delayed-Action Preparations
PubMed: 38225701
DOI: 10.1002/smll.202307281 -
Journal of Psychiatric Research May 2022Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of deficits in cognitive functions which has significant implications for quality of... (Review)
Review
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of deficits in cognitive functions which has significant implications for quality of life. Psychostimulants are demonstrated to improve symptoms of inattention and hyperactivity/impulsivity, however, their impact on cognition remains incompletely characterized. Herein, the aim of this systematic review is to synthesize the extant literature reporting on the effects of psychostimulants on cognitive function in individuals with ADHD.
METHOD
A systematic search of PubMed, Scopus, and Web of Science from inception to July 2021 was conducted. Additional studies were identified through Google Scholar and a manual search of the reference lists of relevant articles. Inclusion criteria were original studies that evaluated the cognitive function of individuals with ADHD taking psychostimulants drugs. We assessed the quality of the included papers using the Newcastle-Ottawa scale (NOS).
RESULTS
A total of 10 studies involving 753 subjects with ADHD and 194 healthy controls were identified and eligible for inclusion. Nine studies evaluated the impact of methylphenidate on cognitive function and one study investigated the use of lisdexamfetamine. Results indicated that attentional deficits such as memory, vigilance, divided attention, phasic and tonic alertness, and focused attention were improved in ADHD patients treated with psychostimulants. The efficacy of psychostimulants in improving other domains of cognition remains inconclusive due to conflicting evidence or insignificant findings (ie. academic performance and executive function). Overall, results indicate that psychostimulants may improve only select domains of cognition (ie. memory and attention).
CONCLUSION
Psychostimulants are reported to improve several disparate aspects of cognition among individuals with ADHD. Further research is needed to better understand the complex relationships between cognition and behavior in ADHD, as well as the impact of medication on these distinct aspects of functioning. Further research is also needed to determine whether the pro-cognitive effect of stimulants would be transferable to other mental disorders.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cognition; Humans; Methylphenidate; Quality of Life
PubMed: 35303614
DOI: 10.1016/j.jpsychires.2022.03.018 -
AAPS PharmSciTech Feb 2021Poor physicomechanical properties and limited aqueous solubility restrict the bioavailability of aceclofenac when given orally. To improve its above properties,...
Poor physicomechanical properties and limited aqueous solubility restrict the bioavailability of aceclofenac when given orally. To improve its above properties, aceclofenac (ACE) was cocrystallized with dimethyl urea (DMU) in 1:2 molar ratio by dry and solvent assisted grinding. The cocrystals were characterized by ATR-FTIR, DSC, and PXRD, and their surface morphology was studied by SEM. There was enhancement in intrinsic dissolution rate (IDR) (~eight- and ~fivefold in cocrystals prepared by solvent assisted grinding (SAG) and solid state grinding (SSG), respectively, in 0.1 N HCl, pH 1.2) and similarly (~3.42-fold and ~1.20-fold in phosphate buffer, pH 7.4) as compared to pure drug. Additionally, mechanical properties were assessed by tabletability curves. The tensile strength of ACE was < 1 MPa in contrast to the cocrystal tensile strength (3.5 MPa) which was ~1.98 times higher at 6000 psi. The tablet formulation of cocrystal by direct compression displayed enhanced dissolution profile (~36% in 0.1 N HCl, pH 1.2, and ~100% in phosphate buffer, pH 7.4) in comparison to physical mixture (~ 30% and ~ 80%) and ACE (~18% and ~50%) after 60 min, respectively. Stability studies of cocrystal tablets for 3 months indicated a stable formulation. Pharmacokinetic studies were performed by using rabbit model. The AUC (37.87±1.3 μgh/ml) and C (6.94±2.94 μg/ml) of the selected cocrystal C1 prepared by SAG were significantly enhanced (p < 0.05) and were ~3.43 and ~1.63-fold higher than that of ACE. In conclusion, new cocrystal of ACE-DMU was successfully prepared with improved tabletability, in vitro and in vivo properties.
Topics: Animals; Crystallization; Diclofenac; Drug Liberation; Drug Stability; Female; Male; Rabbits; Tablets; Urea
PubMed: 33564940
DOI: 10.1208/s12249-021-01938-7 -
The American Journal of Clinical... Apr 2024Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization.
BACKGROUND
Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization.
OBJECTIVES
This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD.
METHODS
In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR).
RESULTS
Of 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN.
CONCLUSIONS
We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.
Topics: Child; Humans; Crohn Disease; Enteral Nutrition; Prospective Studies; Remission Induction; Microbiota; Metabolome; Butyrates; Acetates; Phenylacetates
PubMed: 38569785
DOI: 10.1016/j.ajcnut.2023.12.027 -
The Journal of Adolescent Health :... Apr 2021
Topics: Central Nervous System Stimulants; Child; Health Personnel; Humans; Methylphenidate; Primary Health Care
PubMed: 33781470
DOI: 10.1016/j.jadohealth.2021.01.003 -
Ceska a Slovenska Farmacie : Casopis... 2023In continuation of our published review on general inhalational anesthetics, the current article presents a survey of intravenous agents for general anaesthesia. From...
In continuation of our published review on general inhalational anesthetics, the current article presents a survey of intravenous agents for general anaesthesia. From chemical point of view these compounds belong to structurally diverse categories, such as barbiturates - thiopental (Sodium pentothal®, Trapanal®, Pentothal®), methohexital (Brevital®), and hexobarbital (Evipan®, Hexenal®, Citopan®, Tobinal®); non-barbiturate derivatives - ketamine (Ketalar® Ketaset®), esketamine (Ketanest®), and etomidate (Amidate®, Hypnomidate®), phenolic derivatives - propofol (Diprivan®); steroid derivatives - mixture of alfadolone and alfaxalone (Althesin® in human and Saffan® in veterinary anesthesia); and derivatives of phenylacetic acid - propanidid (Epontol®, Sombrevin®). Most of these compounds are chiral, with the exception of propofol and propanidid. Apart from etomidate and esketamine, they are used in the form of their racemates. Besides their characteristics and mechanism of action, attention is centred also on their chiral properties.
Topics: Humans; Thiopental; Etomidate; Propofol; Propanidid; Anesthetics, Intravenous; Methohexital; Alfaxalone Alfadolone Mixture
PubMed: 37805261
DOI: No ID Found -
Bioorganic & Medicinal Chemistry Letters Feb 2023In this work, a series of novel heterocyclic 2-phenylacetate derivatives were designed and synthesized as water-soluble and rapid recovery hypnotic agents. After...
In this work, a series of novel heterocyclic 2-phenylacetate derivatives were designed and synthesized as water-soluble and rapid recovery hypnotic agents. After introducing heterocyclic ring to the amide group of propanidid, the obtained propanidid derivatives showed greatly improved hydrophilicity and good anesthetic activity. In three animal experiments (mice, rats, and rabbits), compounds 13-15 showed potent hypnotic potency (HD = 7.6, 6.5, 7.4 mg/kg in rabbits, respectively) and higher therapeutic indexes (TI = 17.3, 16.6, 15.2 in rabbits, respectively) than propanidid (TI = 14.7 in rabbits) or propofol (TI = 5.4 in rabbits). Moreover, the recovery time of compounds 13-15 (time to walk, 96.6, 79.6, 81.4 s in rabbits, respectively) were shorter than that of propanidid (124.5 s in rabbits) or propofol (425.3 s in rabbits). The experimental results suggested the potential of compounds 13-15 as water-soluble anesthetics with rapid recovery profile.
Topics: Rats; Mice; Rabbits; Animals; Hypnotics and Sedatives; Propofol; Propanidid; Water; Anesthetics
PubMed: 36736494
DOI: 10.1016/j.bmcl.2023.129165 -
Journal of AOAC International Sep 2023White analytical chemistry (WAC) is a recent approach for evaluating analytical procedures based on their effectiveness in validating results, capacity to be...
Red, Green, and Blue Model-Based Assessment and Principles of White Analytical Chemistry to Robust Stability-Indicating Chromatographic Estimation of Thiocolchicoside and Diclofenac Sodium.
BACKGROUND
White analytical chemistry (WAC) is a recent approach for evaluating analytical procedures based on their effectiveness in validating results, capacity to be environmentally friendly, and economic effectiveness.
OBJECTIVE
The detection of diclofenac sodium (DCF) and thiocolchicoside (THC) simultaneously has been established using a WAC-driven stability-indicating chromatographic method (SICM).
METHODS
For the concurrent stability study of THC and DCF, the suggested chromatographic technique was developed employing safe and environmentally acceptable organic solvents. To identify critical analytical method parameters (AMPs) and analytical quality attributes (AQAs), a design of experiments (DoE)-based screening design was applied. For the DoE-based response surface modelling (RSM) of critical AMPs and AQAs, the Box-Behnken design (BBD) was employed.
RESULTS
A robust SICM was developed by navigating the analytical design space for simultaneous estimation of THC and DCF. IR, NMR, and mass spectral data were used to characterize the degradation products. Red, green, and blue (RGB) models were used to evaluate the suggested method's validation effectiveness, greenness power, and economic efficiency and compared to published chromatographic techniques. The effectiveness of the chromatographic method's validation concerning the International Council for Harmonization (ICH) Q2 (R1) guideline was evaluated using the red model. The analytical greenness (AGREE) evaluation tool and eco-scale assessment (ESA) approach were used to evaluate the green model's methodology. The blue model-based assessment was carried out for comparison of simplicity of instruments handling, cost, and time during sample analysis. The red, blue, and green scores of the techniques were averaged to arrive at the white score of the suggested and reported methods.
CONCLUSION
For the concurrent stability study of THC and DCF, the suggested technique was shown to be validated, environmentally friendly, and cost effective. The suggested approach could be a cost-effective and environmentally friendly analytical technique for determining the stability and monitoring the quality of fixed-dose combinations (FDC) of THC and DCF.
HIGHLIGHTS
Stability-indicating HPTLC method was developed for concomitant analysis of THC and DCF using concepts of DoE and WAC.
Topics: Diclofenac; Chromatography, High Pressure Liquid; Colchicine; Solvents
PubMed: 37137235
DOI: 10.1093/jaoacint/qsad052 -
Enzyme and Microbial Technology Oct 2021Actarit is widely regarded as a safe and effective drug for the treatment of rheumatoid arthritis. There is no report on the bioproductin of actarit so far. In this...
Actarit is widely regarded as a safe and effective drug for the treatment of rheumatoid arthritis. There is no report on the bioproductin of actarit so far. In this study, we demonstrated for the first time the development of an artificial actarit biosynthetic pathway in Escherichia coli. First, 4-aminophenylacetic acid is selected as precursor substrates for the production of actarit. Second, an N-acetyltransferase that can efficiently catalyse the esterification of acetyl-CoA and 4-aminophenylacetic acid to form actarit was discovered. Subsequently, an engineered E. coli that allows production of actarit from simple carbon sources was established. Finally, we further increased the production of actarit to 206 ± 16.9 mg/L by overexpression of shikimate dehydrogenase ydiB and shikimate kinase aroK.
Topics: Biosynthetic Pathways; Escherichia coli; Escherichia coli Proteins; Metabolic Engineering; Phenylacetates
PubMed: 34489018
DOI: 10.1016/j.enzmictec.2021.109858