Primary amoebic meningoencephalitis (PAM) is a deadly disease caused by the free-living pathogenic ameboflagellate Naegleria fowleri, which directly affects the central nervous system. There are only a handful of people throughout the world who have survived this deadly disease. Its alarmingly high mortality rate is due to a lack of a better understanding of the mode of action of the causative agent. Existing treatment options are available in the form of combinatorial drugs, but due to the blood-brain barrier (BBB), a small amount of active substance is reached at the target site. In this study, the membrane-bound, pore-forming protein (N-PFP) of N. fowleri was selected as an anti-pathogenic target. N-PFP, a novel protein of N. fowleri, was docked against several screened-out virtual compounds, based on ADMET criteria, from the Gold and platinum files of the ASINEX library, containing 261120 compounds. For docking analysis, 1-Methyl-4-{(E)-2-[6-methyl-2-(4-morpholinyl)-3-quinolinyl] vinyl} pyridinium was selected as a potential inhibitor. DFT analysis and MD simulations studies were performed, and the mentioned ligand was found to be of promising use for therapeutic purposes against N. fowleri. Further, in vivo and in vitro studies for this compound were recommended as a potential anti-pathogenic molecule.
A straightforward, economic and rapid UVvisible analytical method was developed and validated using the Quality by Design (QbD) approach for the simultaneous estimation of Letrozole and Palbociclib in bulk and synthetic drug mixtures. Letrozole and Palbociclib exhibited maximum absorbance at 240 nm and 220 nm, respectively, when Methanol: 0.2% Ortho Phosphoric acid (50:50% v/v) was used as the solution. The method was optimized using the Design of Experiment (DoE) approach, which helped identify and optimize the impact of critical variables through statistical multivariate analysis and modeling to facilitate continuous improvement. The optimized method was validated according to ICH Q2(R1) guidelines, demonstrating excellent linearity within a concentration range of 2-10 & micro;g/mL, with correlation coefficients (R2) of 0.999 for Letrozole and 0.9996 for Palbociclib. The limits of detection (LOD) for Letrozole and Palbociclib were 0.384 & micro;g/mL and 0.225 & micro;g/mL, respectively, while the limits of quantification (LOQ) were 1.165 & micro;g/mL and 0.684 & micro;g/mL, respectively. The accuracy recovery rates ranged from 98.91-99.56% for Letrozole and 99.86-101.12% for Palbociclib. This QbD-based method offers a systematic and proactive approach to ensuring the quality, reliability, and efficiency of both analytical and manufacturing processes, benefiting the pharmaceutical industry and other sectors.
Compared to the traditional or conventional approach, the quality by design approach to method development, which emphasizes evaluating and minimizing risks, has the potential to produce a method that is more reliable and durable. Abacavir sulfate (ABS) is classified as an antiretroviral. The present work describes a quality-by-design (QbD) methodology-based HPLC technique for quantifying abacavir sulfate. This study utilized an efficient experimental design based on the Box-Behnken design to optimize three key components of an RP-HPLC method: mobile phase composition, pH, and flow rate. Employing a Quality by Design (QbD) approach, critical method parameters were fine-tuned. Chromatographic separation was conducted on an Agilent Technologies ZORBAX Stable Bond-C18, 80 degrees A, 4.6 x 250 mm column, and an isocratic mobile phase comprising methanol: Phosphate buffer (pH 6) in a 70:30 v/v ratio was employed. Using an injection volume of 20 & micro;L and a flow rate of 1 mL/min, detection was carried out at a 287 nm wavelength. The method that was developed showed a linear relationship (r(2) = 0.99). Values for robustness, precision, and ruggedness were all within the expected ranges (%RSD <2% for other parameters, and <1% for system precision). The approach based on Quality by Design (QbD) facilitates the creation of a space for operation and a space for design by integrating an extensive understanding of all method performance attributes and facilitates its optimization, thereby ensuring the consistent quality of the abacavir sulfate. Additionally, it entailed pinpointing potential failure while maintaining a seamless life cycle.
Aloe vera has received a lot of scientific and commercial attention because of its activities in different therapeutic and industrial fields as a drought-resistant succulent plant of great ethnopharmacological importance. Traditionally used to heal wounds and soothe burns, the plant has been shown to further possess anticancer, antifungal, anti-inflammatory, gastroprotective, and hypoglycemic activities, which makes it one of the great versatile gifts of nature to modern healthcare. This review is aimed at providing in-depth views regarding bioactive composition, processing techniques, and functional applications of Aloe vera, especially for its role as a natural alternative to synthetic preservatives and chemical treatments. In the study, an attempt has been made to synthesize a spectrum of recent pharmacological advancements, phytochemical investigations, and industrial reports inculcating the importance of polysaccharides, enzymes, vitamins, and minerals in supporting the bioactivity of Aloe vera. It has been revealed that advances in the field of analytical chemistry through chromatographic and spectroscopic techniques have contributed to the characterization of these bioactive molecules for better quality assurance, product standardization, and the development of new formulations. Besides, the industrial operations that process Aloe vera into juice, concentrate, and powder for extensive use in medicines, cosmetics, nutraceuticals, and functional foods have enhanced antioxidant defense and anti-inflammatory effectiveness. Thus, the review concludes that Aloe vera has great potential to naturally replace synthetic compounds in food preservation, skincare, and treatment purposes. The authors have made a significant contribution by juxtaposing their compositional knowledge with application-oriented perspectives, framing Aloe vera as an environmentally sustainable resource for bioactive compounds. Despite there being issues of variations in plant constituents, challenges around standardization, and the clinical translation of experimental findings, social and practical implications are far-reaching, ranging from producing safer consumer products to establishing greener industrial standards. In conclusion, Aloe vera can be regarded as a plant of historical medicinal relevance and, at the same time, an emerging modern bio-resource with evergrowing application potential in the health, food, and cosmetic industries.
Introduction: Rheumatoid arthritis (RA) is an inflammatory state that damages the articular cartilage, which results in bone deformity and functional loss of joints, eventually causing extreme pain. The key concerns of the drugs currently prescribed for RA are low effectiveness and possible side effects. Therefore, an efficient, yet harmless substitute from herbal sources has gained the special focus of researchers. Sesbania grandiflora Linn is a vital medicinal herb, and the roots are used in traditional medicinal practices for treating arthritic conditions. Objectives: To scientifically validate the anti-arthritic effects of Sesbania grandiflora Linn. roots in Complete Freund's adjuvant (CFA)-inflicted arthritic rodents. Methods: Arthritis was inflicted by subcutaneously injecting CFA (0.1 ml) into the plantar area of the rat's left hind paw. Rats were given oral doses of the ethyl acetate fraction of Sesbania grandiflora roots [EAFSGR] (100 & 200 mg/kg) and diclofenac sodium (4 mg/kg) starting on day 14 and continuing until day 28. Joint diameter, arthritic score, paw volume, thymus and spleen index, hematological variables, liver biochemical, and antioxidant markers were assessed. Further, the ankle joints were examined for radiological and histopathological alterations. Results: Rats treated with the EAFSGR revealed a significant diminution in the arthritic parameters. Further, radiological and histopathological analysis of EAFSGR treatment displayed a significantly reduced swelling and cartilage destruction. Conclusion: The observed experimental outcome may be ascribed to the anti-inflammatory and antioxidant potential of EAFSGR, which could probably be owing to the occurrence of flavonoids. The scientific evidence supporting the traditional use of Sesbania grandiflora roots to treat rheumatoid arthritis has been laid out in this study.
Cyclophosphamide-induced toxicity, including oxidative stress and genotoxicity, is the major concern of cancer chemotherapy therapy. Additional antioxidant supplementation may prevent such a risk. Therefore, in the present study, we assessed the ameliorative effects of theophylline in combination with curcumin on cyclophosphamide-induced oxidative stress and genotoxicity in rats. Wistar albino rats (150-200g) were randomly selected and treated with either distilled water (10 ml/kg), theophylline (20, 50, or 75 mg/kg/day, i.p.), or theophylline + curcumin (25 + 100, 50 + 100, or 75 + 100 mg/kg/day, i.p.) in their respective groups for seven days. After one hour of the last dosing, animals received Cyclophosphamide (10 ml/kg, i.p.) for toxicity induction. Genotoxicity in animals was assessed by the determination of micronucleated bone marrow cells, oxidative stress was evaluated by the determination of enzymatic antioxidant activity (catalase and superoxide dismutase) and the level of lipoperoxidation (malondialdehyde), and liver toxicity was assessed by measuring the serum alanine aminotransferase and aspartate aminotransferase. The results showed that theophylline and its combination with curcumin had significant (P < 0.05) beneficial effects as compared to the Cyclophosphamide control group. They considerably reduced the micronucleated bone marrow cells and restored the oxidative stress and serum liver biomarkers. Additionally, results indicated the potential beneficial effects in the combination group, especially in the theophylline + curcumin (75+100 mg/kg) group to manage the cyclophosphamide-induced toxicity. These results suggest that the combination of curcumin and theophylline enhances the protective effects.
Background: Novasomes, modified liposomal vesicles, enable simultaneous encapsulation of hydrophilic and hydrophobic drugs, offering prolonged and targeted drug delivery. Objective: To develop and characterize a novasomal in-situ gel containing ketoconazole (antifungal) and hydrocortisone (anti-inflammatory) for sustained topical delivery. Methods: Novasomes were prepared by the ethanol injection method and incorporated into a thermosensitive in-situ gel of Pluronic F127 (17-25%) and Pluronic F68 (1-5%). The formulations were evaluated for pH, gelation temperature/time, viscosity, spreadability, DSC, TGA, SEM, and in-vitro release using Franz diffusion cells. Results: Formulations exhibited pH 5.5-6.6 and gelation temperatures 22-35 degrees C, enabling sol-gel transition at skin temperature. DSC showed a sharp endothermic peak at 120 degrees C, confirming thermal stability; TGA indicated 10-12 % weight loss between 40-150 degrees C, suggesting low thermal degradation. SEM revealed spherical vesicles (200-400 nm) with uniform surface morphology. In-vitro release reached 89.78 % for ketoconazole and 90.02 % for hydrocortisone within 11 h. Drug release followed zero-order kinetics (R-2 = 0.93-0.98) and non-Fickian diffusion (n = 0.75-0.89), confirming controlled release behavior. Conclusion: The optimized novasomal in-situ gel demonstrated stable, biocompatible, and controlled topical delivery, highlighting its potential for dual antifungal-anti-inflammatory therapy in dermatological applications.
A substance that comes from a living thing and is found in nature is called a natural product. Daidzein, a member of the isoflavone group with the IUPAC name 7-hydroxy-3-(4-hydroxyphenyl) chromen-4-one, is derived from soybeans and other legumes in either glycoside or aglycone form. Its main chemical components are metabolites produced by gut bacteria, such as trihydroxy isoflavone and equol. Daidzein has proven to have pharmacological effects on various conditions, including cancer diseases, diabetic ailments, cardiovascular ailments, osteoporosis ailments, skin ailments, and neurological ailments. Daidzein is recognized to treat various diseases by acting as an estrogen agonist or antagonist, having direct inflammation-reducing and antioxidant activities, and regulating the cell cycle and apoptotic pathways. In its structural composition and physiological functions, it is classified as a phytoestrogen, a plant-derived compound structurally and functionally analogous to human estrogens, which have been extensively implicated in cancer prevention, bone health maintenance, and the mitigation of various illnesses in postmenopausal women. Therefore, it is good to be developed as a phytopharmaceutical. Emerging strategies for improving Daidzein's solubility, stability, bioavailability, and targeted delivery involve the use of various advanced systems, including polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles, nano complexes, polymeric micelles, polymer-lipid nanoparticles, nanoemulsions, liposomes, nanosuspensions, and self-microemulsifying systems for delivering drugs. Since Daidzein is already taken daily in varied dosages, there should not be a serious safety concern; however the dosage for each indication must be distinct.
Background: Nephrotic Syndrome (NS) is a common pediatric renal ailment in India. Steroids and immunosuppressants are utilized to treat the condition, which has side effects for the patients. One of the fundamental principles of pharmacological treatment is the assessment, diagnosis, prevention, and resolution of Drug-Related Problems (DRPs). Objective: To identify and characterize Drug-Related Problems in pediatric patients with nephrotic syndrome. Materials & Methods: Patients with nephrotic syndrome, with or without co-morbidities, were the subjects of this prospective interventional trial, which was carried out at the pediatric nephrology department of a tertiary care teaching hospital. 88 patients from both the inpatient and outpatient departments, ranging in age from 4 to 18, participated in the study. The study excluded individuals with cancer and those who did not provide their consent. Along with usual care, the patients received a Patient Information Leaflet (PIL) and patient counseling. Intervention was used to identify and address the causes and issues related to drug-related problems. Results: Among 88 recruited patients, 56 (64%) were male and 32 (36%) were female. According to the data, it was confirmed that the male population has a higher prevalence than the female population. Out of 88 recruited patients, Drug-Related Problems (DRPs) were found in 52 (59.09%) patients, and DRPs were absent in 36 (40.91%) patients. Drug-Related Problems (DRPs) were solved by providing pharmacist intervention. Conclusion: Clinical pharmacists are needed to provide the knowledge and counselling to the patient for the betterment of their lives.
Alcohol-induced liver cirrhosis, a serious condition caused by chronic excessive alcohol consumption, results in severe liver damage characterized by inflammation, fibrosis and oxidative stress. This study investigates the hepatoprotective qualities of Bryonia lacinosa L (BL), a plant traditionally used for medicinal purposes, using network pharmacology and molecular docking techniques. Nine bioactive compounds were screened according to Lipinski's rule of five, which evaluates drug-likeness, and were predicted to interact with 146 genes linked to liver cirrhosis. Pathway analysis revealed that critical signaling pathways such as Phospholipase D, mTOR and PI3K-Akt were significantly impacted. These pathways are crucial in regulating oxidative stress, cell survival and apoptosis, processes essential for cirrhosis development. Additionally, HIF-1 and NF-kappa B signaling pathways were also modulated, indicating a wider influence of the plant bioactives on liver health. Molecular docking revealed strong interactions between BL compounds, particularly quercetin and Corynan-17-ol,18,19-didehydro-10-methoxy, with proteins like PIK3R1 and NFKB1. Molecular dynamics simulations substantiated the robustness of these protein-ligand complexes, emphasizing the therapeutic viability of BL. Antioxidant assays, including DPPH radical scavenging, total flavonoid and phenolic content evaluations, validated the extract's antioxidative properties. LC-MS (Liquid chromatography-mass spectroscopy) analysis identified terpenoids and flavonoids as key bioactive compounds. By modulating critical molecular pathways and reducing oxidative stress, BL exhibits hepatoprotective potential against alcohol-induced liver cirrhosis. These findings highlight BL as a promising candidate for liver health. However, additional in-vitro and in-vivo investigations are crucial to establish its safety and efficacy for therapeutic applications.
The geographical remoteness, as well as the sparse population of most Asian Far Eastern regions of Russia, and the difficulties of receiving medical care, especially in small towns, can lead to a high frequency of independent use of antibiotics by the population; accordingly, there will be errors in drug therapy and an increase in antibiotic resistance. Therefore, the purpose of this study was to analyze changes in the behavior of patients in the Far East in relation to antibacterial drugs over 20 years. A sociological survey was conducted in 2005 and 2025. Statistical analyses were performed using the Kendall and Spearman rank correlation coefficient. The proportion of patients who purchase antibiotics without a doctor's prescription over the study period of 20 years decreased from 77% to 49%. At the same time, the share of respondents who use antimicrobial drugs without a doctor's prescription, on the contrary, increased from 42% to 61%. The most common reason for the use of antibiotics in 2005 was tonsillitis, and in 2025, there was an acute respiratory viral infection-which is an erroneous therapy strategy. The most sought-after antibiotics are Amoxicillin and Amoxicillin + Clavulanic acid. The proportion of mistakes of respondents at the mention of the necessity to use antibiotics in case of fever, as well as at the choice of the duration of the course of using the antibacterial drug, significantly increased. The results obtained demonstrate the need to strengthen restrictive and educational measures on the part of the state, as well as medical and pharmaceutical specialists.
Background: Hepatocellular carcinoma (HCC) is the prevalent and deadliest type of liver cancer across the globe. Owing to drug resistance and adverse effects, the available therapies have certain limitations, which offer a window to explore alternative therapeutic options based on natural sources. Based on traditional and modern practices, a primary source of applied medication relates to botanical origin due to biodiversity. This provides insight into evaluating the undiscovered features of plants and their relevant products to utilize their impact in the medicinal field, particularly in cancer treatment. Aim: The present study aimed to investigate the anti-proliferation and anti-angiogenic potential of Euphorbia Giulia (EN) extract against Hepatocellular Carcinoma Cells (HepG2). Methods: In-vitro anti-proliferative and anti-angiogenic activities were performed on the HepG2 cell line through different assays like MTT, crystal violet, trypan blue, and scratch assay. Results: The results showed that EN extract significantly decreased proliferation and angiogenesis compared to untreated cells. The MTT assay exhibited a significant decline in the growth rate of the proliferating HepG2 cells as their metabolic activity was halted with EN extract. The crystal violet and trypan blue assays revealed that EN extract significantly inhibited cell viability and cell death, respectively. Moreover, when treated with EN extract, the scratch assay displayed a slower gap closure, which manifested its ability to promote angiogenesis. Conclusion: Conclusively, EN displayed significant anti-proliferative and anti-angiogenic effects on HepG2 cells, and its phytochemicals could be potential candidates for the treatment of HCC after further validations.
Mucoadhesive drug delivery systems have been thoroughly investigated for their capacity to extend the residence time of the dosage form at the absorption site, thereby improving bioavailability and patient compliance. This study aimed to develop and evaluate mucoadhesive tablets containing the anti-Parkinson's drug piribedil, using different mucoadhesive polymers. The matrix tablets were prepared by the direct compression method and evaluated for various physicochemical properties, in vitro drug release, and ex vivo mucoadhesive strength. Pre-compression evaluations, including bulk density, tapped density, angle of repose, compressibility index, and Hausner's ratio, demonstrated good flow properties of the powder blends. Post-compression analyses confirmed uniformity in tablet hardness, weight variation, thickness, drug content, and friability, all within acceptable limits. The in vitro drug release profile varied with polymer type and concentration. Tablets with xanthan gum exhibited >90% drug release within 6 hours, while those with HPMC K4M and chitosan showed sustained release profiles. Mucoadhesive strength and swelling indices indicated optimal performance, with the formulation containing HPMC K4M exhibiting superior bioadhesion and controlled drug release. The stability studies conducted on the optimized formulation (F6) revealed consistent drug content and no significant degradation over three months, adhering to ICH guidelines. These findings highlight the potential of buccal tablets for effective and patient-friendly drug delivery.
