Rebamipide at 80 mg/kg oral twice daily was previously found effective against a hemiparkinson’s model in rats. However, the high dose and frequency limit its advantages. Therefore, for the first time, a novel dosage form of rebamipide as transdermal patches was formulated, characterized and evaluated againt a rodent model of Parkinson’s disease. Four different transdermal formulations containing rebamipide were prepared using the solvent casting method (4 mg rebamipide/patch). Transdermal patches were observed to be uniform in terms of physicochemical characteristics. Rebamipide was administered through both the oral (80 mg/kg twice daily) and transdermal route (one patch daily) from Day-4 to Day-27 after unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in male rats. Patches increased levels of dopamine, dopamine transporters, tyrosine hydroxylase, and glucocerebrosidase enzymatic activity and decreased α-synuclein pathology and motor deficits in 6-OHDA-infused rats. All the animal-related parameters include 6 rats per group, and behavioral studies include 12 rats per group. Repeated measures of two-way ANOVA was used for the analysis of behavioral parameters and ex vivo permeability. Remaining in vivo parameters, physicochemical characteristics (weight, thickness, folding endurance, surface pH, swelling, moisture loss and drug content uniformity) and skin irritation studies were analyzed by one-way ANOVA. Rebamipide concentration using HPLC was analyzed by an unpaired t test. The effects of rebamipide patches and oral groups against 6-OHDA toxicity were similar and the concentration of rebamipide in plasma and cerebrospinal fluid of both groups was also observed to be the same. These preclinical findings suggest that a low rebamipide dose administered once daily through a newly-prepared transdermal patch (4 mg drug/patch) showed similar potential as a high oral rebamipide dose (80 mg/kg) administered twice daily in rats against 6-OHDA toxicity. Further studies including detailed pharmacokinetic and mechanistic data are required in order to translate the information successfully from animal to clinical studies.
In this study, antioxidant potential, anticholinesterase activity, and elemental contents of Chlorophyllum rhacodes were evaluated. In order to determine the antioxidant capacity, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), DPPH radical scavenging activity, and FRAP ferric reducing power analyses were applied. According to the obtained results, the TAS value was determined as 3.125 +/- 0.060 mmol/L, the TOS value as 6.821 +/- 0.062 & micro;mol/L, the OSI value as 0.218 +/- 0.003, DPPH activity as 55.430 +/- 1.438 mg TE/g, and the FRAP value as 72.540 +/- 1.461 mg TE/g. These data revealed that C. rhacodes showed a significant level of antioxidant activity. In the evaluation of anticholinesterase activity, inhibitory effects against AChE and BChE enzymes were determined, and IC50 values were found as 94.330 +/- 1.536 & micro;g/mL and 128.397 +/- 1.556 & micro;g/mL, respectively. These results show that C. rhacodes exhibits limited inhibitory effect on these enzymes but may have a certain level of anticholinesterase potential. According to the results of elemental analysis, Cd (14.78 +/- 1.53), Cr (33.17 +/- 1.42), Mn (7.35 +/- 0.52), Cu (155.77 +/- 2.34), Fe (469.30 +/- 15.75), Pb (6.98 +/- 0.54), Ni (3.66 +/- 0.31) and Zn (76.18 +/- 2.25) mg/kg levels were detected in mushroom samples. In particular, it was observed that Cd and Cu levels were above the upper limits specified in the literature. This finding shows that C. rhacodes tends to accumulate some heavy metals and may be highly sensitive to environmental pollution. In conclusion, C. rhacodes exhibits a biologically remarkable profile with certain antioxidant and anticholinesterase activities and can also be considered as a potential indicator species in the biological monitoring of environmental metal exposure.
Coumarin derivatives are known for their broad biological activities, particularly their ability to influence oxidative stress pathways. In this work, a new series of 7-(2,3-epoxypropoxy)coumarin derivatives was synthesized and fully characterized by NMR and HRMS. The structural modification introduced a 3'- ethoxy-2'-hydroxypropoxy fragment, and the compounds were evaluated for their ability to modulate hydroxyl and methyl radical formation in the Fenton reaction using Electron Paramagnetic Resonance (EPR) spectroscopy. Comparative analysis revealed that derivative 1 and its precursor a (6-acetyl-4-methyl-7-(oxiran-2-ylmethoxy)-2H-chromen-2-one) exhibited the most pronounced radical-scavenging activity, demonstrating stronger antioxidant effects than their corresponding substrates. These findings highlight coumarin epoxide derivatives as promising scaffolds for redox-modulating agents, and confirm the utility of EPR as a sensitive tool for probing antioxidant potential.
The objective of this study was to develop and optimize gastroretentive floating tablets of dapsone using a Quality by Design approach to enhance therapeutic efficacy in leprosy treatment. The tablets were prepared by direct compression using a322 factorial design, with HPMC K15M (150-250 mg) and NaHCO33 (15-25 mg) as independent variables. The formulations were evaluated for compression parameters, floating characteristics, and drug release profiles, with optimization focused on floating lag time (Y1) and drug release at 12 hours (Y2) as key responses. Further studies assessed release kinetics, formulation stability, and a comparison with a marketed product. The optimized formulation (RF3), composed of 150 mg HPMC K15M and 25 mg NaHCO3, 3 , exhibited excellent flow properties (Carr's index: 15.25%, angle of repose: 26.84 degrees), desirable floating behavior (lag time: 64 seconds, duration: 11.4 hours), and sustained drug release (98.4% over 12 hours). The drug release followed the Higuchi model (R22=0.9975) with a non-Fickian transport mechanism (n=0.75). Stability studies under accelerated conditions (40 degrees C/75% RH for 6 months) confirmed drug content retention of 98.24% and a consistent release profile (97.4% at 12 hours). Overall, the optimized gastroretentive floating tablet formulation demonstrated satisfactory in vitro performance and stability, suggesting promising advantages over conventional dosage forms through extended gastric retention and controlled drug release. While these findings support the potential of this novel formulation for modified dapsone delivery, comprehensive in vivo studies are necessary to validate its therapeutic benefits over existing therapies.
Liquisolid systems present an effective technique for improving the dissolution rate , oral bioavailability of poorly water-soluble drugs. The objective of this study is to formulate and evaluate diacerein liquisolid compacts using Tween 80 as the liquid vehicle, Neusilin and Fujicalin as carriers , Aerosil 200 as a coating material. Sodium starch glycolate and magnesium stearate were used as disintegrants and lubricants, respectively. Pre- and post-compression parameters such as flow properties, hardness, friability, drug content, and disintegration time were measured. The in vitro release characteristics of the pure drug, marketed capsules (as reference), and liquisolid technique (test sample) were studied. Among all the formulations, FSC3 had the highest dissolving efficiency (DE) of 53.109% at 60 minutes, exceeding the marketed product's DE of 44.972%. FTIR analysis revealed no drug-excipient incompatibility, and all tested formulations fulfilled pharmacopeial requirements for flow and mechanical characteristics. Overall, the study demonstrates that the liquisolid technique significantly improves the dissolution of diacerein, indicating its potential to boost the physicochemical properties of poorly soluble drugs.
The rising demand for natural cosmeceuticals is primarily attributed to their minimal side effects and their potential as alternatives to synthetic drugs. Numerous plant-derived compounds have been identified with properties beneficial for skin care, including whitening, anti-aging, and anti-wrinkle effects, as shown in the graphical abstract. This review comprehensively evaluates the efficacy of various herbal remedies for wrinkle treatment, drawing evidence from clinical studies, experimental research, and traditional practices. The study is aimed to identify medicinal plants with substantial scientific support for their therapeutic benefits, particularly in wrinkle reduction. An extensive literature search was conducted using databases such as PubMed, Google Scholar, Scopus, Web of Science, and ScienceDirect. The Plant List database was also consulted to confirm the scientific names, plant families, traditional uses, and active constituents of each plant. The analysis revealed 23 plant species from 19 different families that are traditionally used for managing symptoms of premature aging, including wrinkles and pimples. These plants were reviewed for their mechanisms of action, bioactive constituents, availability, and potential applications in cosmetic formulations. Scientific studies have confirmed that phytoconstituents possess anti-inflammatory, photoprotective, and anti-wrinkle properties, with proven inhibitory effects on wrinkle-related enzymes such as elastase and collagenase. Key botanicals such as Diospyros kaki, Ipomoea carnea, Calendula officinalis, Ocimum basilicum, and Moringa oleifera have shown significant cosmeceutical potential. Overall, the findings suggest that phytoconstituents from medicinal plants represent promising and potentially superior alternatives to synthetic agents for the development of effective anti-wrinkle treatments.
The phrase "drug induced disease" refers to an unintentional pharmacological side effect that causes mortality and morbidity and symptoms severe enough to necessitate hospitalization or medical attention. Anticoagulants, anticonvulsant, anti-seizure agents, antiepileptics, and antihistamines are among the drugs whose fetal developmental toxicity has been shown by epidemiological studies. These drugs can cause miscarriage, birth defects, and other adverse pregnancy outcomes. The primary method for diagnosing drug-related disorders in patients is the patient's or their family's history of drug use. The term "teratogenicity" describes the incidence of congenital defects brought on by teratogenic substances. Various pharmacogenetics has been studied in relation with the teratogenic mechanisms including folate antagonism, oxidative stress, inhibition of the angiotensin-converting enzyme (ACE) and angiotensin II receptor. Physical factors like ionizing radiation and toxic metals, chemical exposures, and pharmaceutical treatments including thalidomide, excessive vitamin A, corticosteroids, antiepileptic, anti-seizure, and antihypertensive medications are some of the sources of teratogenic abnormalities. To receive treatment for drug-induced problems, a patient must first notify a physician. During the course of the two-year trial period, 2381 ADR (Adverse drug reaction) events were reported in total, and 926 (38.89%) of them were drug-induced diseases.
Propolis, an intriguing natural material synthesized by bees, is characterized by its intricate resinous blend, which boasts a remarkably varied chemical composition. This unique blend contains various bioactive compounds that contribute to its numerous health benefits. The ability of propolis to combat inflammation, infections, and oxidative stress has made it a powerful candidate for enhancing overall health, with particular relevance to oral care practices. As the researchers continue to unravel the diverse properties of propolis, it is becoming an increasingly intriguing subject for clinical studies. In the present review, we aim to summarize and present the most recent data from clinical trials on the potential of propolis in the oral cavity diseases treatment and prevention. Propolis can be helpful in decreasing dental caries, effectively treating periodontitis, managing dentin hypersensitivity, treating gingivitis, and promoting overall oral hygiene. The results of our research suggest that propolis could serve as a valuable adjunct to dental therapies, potentially improving traditional methods and leading to enhanced outcomes for patients.
Dengue is the most rapidly spreading vector-borne disease in the world. An estimated 2.5 billion people live in dengue-endemic countries. Most cases of dengue are asymptomatic; however, the disease can progress to a severe cases with plasma leakage, hemorrhage, and shock. The treatment options are limited and are focused mostly on supportive care. Procalcitonin is regarded as a biomarker specific for bacterial infections. The current literature contains only five papers addressing the topic of the clinical relevance of serum procalcitonin in patients with dengue. Serum procalcitonin levels tend to be elevated in patients who experience organ failure, shock, or dengue hemorrhagic fever; however, this difference was not statistically significant in all studies. Serum procalcitonin demonstrated strong diagnostic utility for detecting bacterial coinfection or bacteremia, and can be used to exclude bacteremia in dengue patients. The majority of the reviewed studies involved small sample sizes, which often precluded reaching statistical significance. The utility of serum procalcitonin as a diagnostic marker in patients with dengue remains insufficiently explored, and further research is necessary to fully understand its clinical role.
Nearly 50% of the world's population struggles with excess body weight. Elevated BMI contributed to about 5 million deaths from non-communicable diseases in 2019 and is a defined negative predictor of numerous diseases, mainly on the cardiovascular side. The purpose of this article is to characterize possible new drug breakthrough points for obesity therapy and also to describe already available approaches. Pubmed and clinical trials databes was searched using obesity, GLP-1, GIP, glucagon, amylin as the key words. To date, five drugs have been registered in the European Union for the treatment of obesity. Of these, Glucagon-like peptide-1 agonists administered by subcutaneous injection are the most effective. In order to further increase the effectiveness of overweight therapy, research is underway to combine different mechanisms of action in a single preparation. Promising directions are substances that activate receptors for glucagon and amylin, which may represent new points of action in the treatment of obesity. A preparation combining agonism of glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and glucagon receptors - retatrutide - showed a significant weight reduction effect of 24% over 48 weeks. However, further studies including comparative analyses are needed to reliably assess their efficacy and safety.
Cosmeceuticals, a combination of medicines and cosmetics, provide therapeutic advantages using advanced drug delivery mechanisms. The products improve not only skin health but also beauty. Most of the cosmeceuticals used transdermal delivery systems, which have limitations in absorption and penetration. Advanced drug delivery systems, such as nanostructured lipid carriers (NLCs), have great potential in avoiding the epidermal barrier toward enhanced delivery and targeted distribution of active ingredients. Nanostructured Lipid Carriers are formed by mixing spatially incompatible long and short-chain lipids using various formulation techniques. Nanostructured lipid carriers can efficiently encapsulate active ingredients and ensure controlled release and targeted action. These benefits, combined with the properties of the encapsulated substances, contribute to improved skin hydration, moisturization, and anti-ageing effects when applied in cosmeceuticals. NLCs have shown potential in hair care, sunscreens, and UV protection applications because they enhance the delivery and stability of active ingredients. Despite these benefits, detailed information on the potential limitations of NLC systems remains underreported. Current research emphasizes the importance of conducting thorough in vitro toxicity studies per the Organization for Economic Co-operation and Development recommendations to assess their safety profiles and identify possible concerns. More research is also essential to close knowledge gaps and guarantee that the safety and effectiveness of NLC formulations are fully proven before moving on with clinical trials or regulatory evaluations.
Nifedipine (NIFE) is a potent first-generation dihydropyridine calcium channel antagonist that belongs to the BCS-II drug. It inhibits calcium entry through L-type channels and disrupts the Ca-calmodulin complex, which ultimately blocks myosin light chain kinase activation, resulting in vasodilation, reduction in blood pressure, and negative chronotropic effect, thus slowing the heart rate. NIFE was used in the treatment of hypertension and angina. However, physicochemical properties, pharmacokinetic profile, mechanism of action, and therapeutic efficacy explain the widespread use of medication in various medical conditions. With a primary focus on its calcium channel-blocking properties, NIFE has demonstrated therapeutic efficacy in addressing classical vasospastic disorders, such as Raynaud's phenomenon, by modulating vascular function and reducing the episodes of digital ischemia. NIFE has been proven beneficial in ureteral stones by increasing their passage rates and in migraine by producing vasodilation. NIFE exhibits therapeutic effects by inhibiting proliferation and metastasis in colorectal cancer through reactivating tumour immunity. Similarly, it has great potential in obstetrics, as it effectively manages preterm labor by delaying the delivery and optimizing fetal conditions. Moreover, its applications can expand into evolving domains, such as achalasia, glaucoma, and chilblains, and potentially as an effective intervention against COVID-19.
High-altitude illness is a condition occurring in individuals at high altitudes (above 2500 meters above sea level) resulting from inadequate acclimatization to the unique environment. Initially, the illness manifests as a set of nonspecific symptoms of acute mountain sickness (AMS). Rapid ascent to altitudes above 4000 meters can lead to severe complications, such as high-altitude cerebral edema (HACE) or high-altitude pulmonary edema (HAPE). With appropriate prevention measures, gradual ascent, and the use of medications such as acetazolamide, the risk of developing AMS can be significantly reduced. The mechanism of action of acetazolamide involves increased excretion of bicarbonates by the kidneys, leading to acidification of the blood (a decrease in blood pH). This process stimulates the respiratory center, increasing minute ventilation and improving oxygenation at high altitudes. Clinical studies have demonstrated that using acetazolamide at doses of 125 mg twice daily is effective in preventing AMS. Acetazolamide is well-tolerated, although it may cause side effects such as paresthesia, taste disturbances, or mild diuretic effects. Its use can significantly enhance the body's ability to adapt to high altitudes. In life-threatening conditions such as HAPE and HACE, the treatment primarily relies on other methods. Due to the increasing prevalence of travel to high-altitude regions, physicians and rescue workers are encountering this issue more frequently. The aim of this study is to compile current knowledge on the use of acetazolamide in altitude sickness.
Currently, pharmaceutical chemists focus on investigating an increasingly wide range of compounds as potential new drugs, including substances of natural origin and those obtained by chemical synthesis. Due to the advancements in the experimental techniques, modern science possesses numerous tools for discovering new types of biologically active molecules. For example, the development of chemical synthesis methods has created a possibility to reach completely new arrays of compounds, as potential candidates of some new drugs. In this context, sulfoximines have quite recently emerged as a promising and versatile class of organosulfur compounds with interesting pharmacological properties. In this article, we present an overview of the key features of sulfoximine functional group, including its unique pharmacochemical profile, that may elevate its potential in medicinal chemistry. We also briefly discuss examples of synthetic approaches to obtain new derivatives containing this functional group, with particular attention to both classical and modern synthetic protocols. Finally, selected examples of biologically active sulfoximines developed by various research groups are highlighted, demonstrating their potential applications in drug discovery.
Polymers are a group of compounds commonly encountered in everyday life. However, due to the increasing incidence of cancer, allergies and progressive environmental pollution, it is becoming essential to design new chemical compounds that would be safe. Particular attention is paid to the resorbability of compounds and their biodegradability. These features seem to be particularly important in broadly understood orthopedics, surgery or aesthetic medicine. This article, which is a continuation of the undertaken topic, presents examples of polymers and their application, among others, during surgical operations, orthopedic procedures or broadly understood dermatology. Particular emphasis is given to specific properties of the polymer that determine its usefulness in a given medical discipline.
Insulin, produced by pancreatic β-cells, is a critical anabolic hormone that plays a pivotal role in the regulation of carbohydrate metabolism. Dysregulation of insulin secretion can pose significant threats to health and life, underscoring the importance of its discovery. The introduction of insulin as a therapeutic agent revolutionized diabetes management. Currently, human insulin and its analogs, manufactured through advanced genetic engineering techniques, are widely used. Despite more than a century of clinical use, efforts to improve insulin formulations continue, aiming to enhance patient comfort and reduce the frequency of injections. Insulin is also employed in the management of acute conditions, such as diabetic ketoacidosis and hyperglycemic hyperosmolar state, where intravenous administration is used to lower blood glucose levels effectively. Additionally, insulin is effective in the treatment of hyperkalemia and in cases of poisoning with calcium channel blockers and β-receptor antagonists. In these scenarios, insulin has the highest therapeutic recommendation class. High-dose insulin euglycemic therapy (HIET) is implemented using doses of approximately 1 IU/kg body weight, regardless of patient age, with careful maintenance of euglycemia. HIET is also considered in cases of poisoning with metal phosphides and refractory shock. Positive outcomes have been reported in the literature for patients treated with high-dose insulin for caffeine poisoning and venlafaxine toxicity. These isolated reports highlight the need for further research and development of insulin therapy in acute medical conditions, potentially expanding its applications beyond traditional indications.
The importance of local anaesthetics in dentistry cannot be overestimated. Being the most commonly used drugs in dental practice, these medicines are simply indispensable, as they allow for intra-operative and partly post-operative pain control in procedures performed. The injectable agents, currently employed in dentistry, belong, almost exclusively, to the amino-amide class. The paper focuses on articaine — a peculiar amino-amide local anaesthetic, which exhibits exceptional features distinguishing it from other drugs in the group and endearing it to dental practitioners all over the world, at the same time. The structure of the drug is presented and characteristics arising from its unique attributes are discussed. The article covers the practical aspects of articaine use in various fields of dentistry and oral surgery and arising prospects for the future. Despite the wide safety margin of the agent, articaine, like any other local anaesthetic, may induce unwanted side-effects, which were also described here, and their management was briefly presented.
Osteoarthritis (OA) is known as a debilitating form of arthritis that is marked by progressive degradation of cartilage, synovial inflammation, chronic pain, and subchondral bone remodeling. OA causes progressive stiffness and decreased mobility, significantly affecting the overall quality of life of the person affected. In spite of vast research in this area, the present pharmacological interventions are purely symptomatic. Consequently, there is an expanding interest in exploring multidimensional targeting of pathophysiological pathways using natural treatment options, while improving patient compliance by enhancing the safety profile. The current review focuses on a novel, innovative, and conceptual formulation that is designed by the authors with scientific-evidence-packed natural compounds for management of OA. This review aims to evaluate the rationale behind formulating a conceptual novel tablet consisting of Cissus quadrangularis, Boswellia serrata, propolis, and palmitoylethanolamide (PEA) for definitive management of OA. To our knowledge, this is the first article to explore this combination which is designed in such a way that it targets oxidative stress, inflammation, cartilage destruction, and pain in OA simultaneously in a synergistic manner. In contrast to conventional treatment options, which primarily provide symptom relief, this novel conceptual formulation could offer analgesic, chondroprotective, and regenerative effects with a reasonable safety profile, making it suitable for long-term use. This formulation has the potential to emerge as an effective and safer alternative for treatment of OA, by helping to bridge the gap between integrative and conventional medicine.
Opicapone, a once-daily catechol-O-methyltransferase (COMT) inhibitor, is used as an add-on to levodopa treatment to manage motor fluctuations in Parkinson’s Disease (PD). Although its efficacy in extending ON time is established, the safety profile of opicapone, particularly regarding adverse events and dyskinesia, remains under investigation. A systematic review and meta-analysis were performed with randomized controlled trials (RCTs) and open-label trials that investigated the incidence of adverse events in individuals with PD treated with opicapone as an add-on to levodopa treatment. The systematic search was conducted in PubMed, Cochrane, and EBSCO Megafile databases. Random-effects meta-analyses calculated risk ratios (RR) for adverse events, serious adverse events, adverse events leading to discontinuation, and dyskinesia. Certainty of evidence was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Six studies (n = 2705) were included, with four RCTs eligible for meta-analysis. Opicapone at both 25 mg and 50 mg doses was associated with a significantly increased risk of dyskinesia compared to placebo (25 mg: RR = 2.47; 50 mg: RR = 2.75). No statistically significant differences were found for overall adverse events, serious adverse events, or adverse events leading to discontinuation. Heterogeneity across studies was generally low. Opicapone, as an add-on to levodopa treatment, shows a favorable overall safety profile, with the primary concern being an increased incidence of dyskinesia. Clinicians should monitor for motor complications and adjust levodopa dosing as needed. Further research is needed to refine dyskinesia management strategies and evaluate long-term safety outcomes.
Co-amorphous systems (CAMS) have been studied as a solubility enhancement tool for the drugs facing solubility and bioavailability challenges. They have also been used to improve the stability with respect to amorphous state which is responsible for higher dissolution of the drug. This study aimed to obtain the mechanistic insights into co-amorphous formulation and improvement of the solubility of Darunavir, thereby establishing bioavailability advantage over the pure drug. To select the co-former, various virtual screening methods was employed such as the Hansen Solubility Parameter and Flory-Huggins Interaction Parameter, leading to the selection of Para-Amino Benzoic acid as a co-former. Various methods for preparation such as solvent evaporation, quench cooling and spray drying techniques were employed for co-amorphization. Based on dissolution performance the SE method was selected as it showed a 36.9-fold improvement in solubility, while dissolution studies demonstrated a 3.39-fold improvement. Dissolution studies of CAMS prepared by solvent evaporation method in 1:1 molar ratio established 1.19- and 1.25-fold better performance than 1:2 and 2:1 molar ratio, respectively. The prepared CAMS was characterized by FTIR, DSC, PXRD. Study of CAMS prepared by ex-vivo results demonstrated a 1.84-fold superior permeation, while in-vivo results confirmed a 1.72-fold improvement in oral bioavailability. Further, one-way analysis of variance (ANOVA) was applied to results of in vitro drug release, ex vivo permeation and in vivo pharmacokinetic study followed by Dunnett’s test, which revealed that the increase in drug release, permeation and oral bioavailability of CAMS, were statistically significant at a probability level of p < 0.05 when compared with the pure crystalline drug darunavir.
