Iranian Journal of Pharmaceutical Sciences
"Iranian Journal of Pharmaceutical Sciences (IJPS)" is the official journal of Pharmaceutical Sciences Research Center, an organization of scientists and pharmacists committed to the improvement of Pharmaceutical sciences through the advancement of research, academics, and scientific publications. Every article that we publish is open access and freely available online to anyone. Please feel free to subscribe to our feed, Register into our website, submit your pharmaceutical sciences related manuscripts or inform us if you are available as a reviewer and join us!
Atropine Alone vs. Atropine Plus Pralidoxime for Organophosphorus Poisoning: A Randomized Controlled Trial
Organophosphate (OP) poisoning accounts for approximately 300,000 annual global deaths. Despite WHO recommendations, pralidoxime's efficacy alongside atropine for OP poisoning treatment remains uncertain. This study aimed to evaluate whether the addition of pralidoxime to atropine and supportive care provides clinical benefits. A double-blind, randomized, placebo-controlled trial was conducted at Loghman Hakim Hospital in Tehran, Iran, between April 2022 and March 2023. Patients with OP poisoning were randomly allocated to either an intervention group (pralidoxime plus atropine) or a control group (atropine alone). The primary outcome was patient recovery. Secondary outcomes included duration of hospitalization and alteration in paraclinical parameters such as VBG, serum cholinesterase, sodium, potassium, blood glucose, etc., within the initial four hours post-treatment. Sixty participants were included, with 30 patients in each group. The odds of recovery were significantly higher in the control group compared to the intervention group (OR: 4 [95%CI: 1.3-12.6], p = 0.018). However, this difference became nonsignificant after adjusting for baseline discrepancies (adjusted OR: 6.5 [95% CI: 0.96-43.96], p = 0.054). Hospitalization duration was significantly shorter in the control group (6.23 vs 13.31; mean difference: 7.08 [95% CI: 2.17-11.98], p = 0.006). There was no significant between-group difference regarding alteration in paraclinical parameters during the first four hours post-treatment. The addition of pralidoxime to atropine did not improve survival or reduce hospitalization in OP poisoning. The reasons for this lack of efficacy remain unclear. Further multi-center randomized controlled trials with larger sample sizes are needed to investigate alternative dosing regimens or other oximes.
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Catechin Hydrate Mitigates DEHP Toxicity by Attenuating Oxidative Stress in Mesenchymal Stem Cells
Since di-2-ethylhexyl phthalate (DEHP) from medical bags and tubes induces oxidative stress in bone marrow mesenchymal stem cells (BMSCs). Therefore, the aim was to use Catechin hydrate (CH) as a natural antioxidant to prevent lipid peroxidation. In this experimental study, BMSCs were treated with 0.063, 0.125, 0.25, 1, and 10 μM of CH for 4 days. Based on its effect on cell viability, 0.25 μM of CH was selected for further analysis. The cell was treated with 0.25 μM of CH as well as 100 and 500 μM of DEHP individually and in combination for 4 and 8 days to study cell viability, population doubling number (PDN), total protein, malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT) and superoxide dismutase (SOD) activity, nucleus and cytoplasm morphology and expression of Nrf2 and NFkB genes. Viability and proliferation ability of BMSCs were significantly (p<0.0001) decreased by DEHP in a dose and time-dependent manner, while CH caused a significant increase (P<0.0001). DEHP decreased (P < 0.0001) total protein, TAC, and the activity of antioxidant enzymes, and increased (P < 0.001) the MDA level, as well as causing morphological changes. In addition, DEHP caused a significant decrease in NF-κB and an increase in Nrf2 expression. Although CH in simultaneous treatment was able to completely compensate for the toxic effect of DEHP at 100 μM, especially at 8 days, when compared to the control, it could not prevent the toxic effect at 500 μM. In addition, CH was able to compensate for the imbalance of the NFkB/Nrf2 caused by DEHP. The consumption of fruits, vegetables, and especially tea, which contains a low concentration of CH, may be an alternative medicine for patients undergoing hemodialysis and blood transfusion.
Melatonin versus Zinc for Sleep Disorders in Cirrhotic Patients: A Randomized Double-Blind Pilot Trial
Given the absence of an established gold standard for managing sleep disturbances in patients with cirrhosis, the present randomized double-blind trial was conducted to evaluate the efficacy and safety of melatonin (5 mg/night) versus zinc (50 mg/night) in alleviating sleep disorders within this population. A total of 42 eligible participants were enrolled and randomly assigned to receive either melatonin or zinc. The Pittsburgh Sleep Quality Index (PSQI) was evaluated at baseline and again after one month of treatment. All participants tolerated the interventions well, and no dropouts occurred during the study period. Statistical analysis revealed that PSQI scores significantly improved in both treatment groups compared with baseline (p = 0.001 for both the melatonin and zinc groups). However, there was no statistically significant difference between the two interventions in PSQI scores at the end of the trial (p = 0.936). Based on the observed efficacy and tolerability, both melatonin at 5 mg nightly and zinc at 50 mg nightly may be considered as viable options for addressing sleep disorders in individuals with cirrhosis.
Polymer-Dependent Performance of Mucoadhesive Chlorhexidine Gels: A Comparative Evaluation of HPMC and Chitosan Formulations
Chlorhexidine (CHX) is a widely used antiseptic agent in oral healthcare. However, conventional mouthwash formulations are limited by poor retention time on mucosal surfaces. This study aimed to develop and compare two mucoadhesive CHX 0.2% gels using Hydroxypropyl Methylcellulose (HPMC) and chitosan polymers to improve drug retention and release performance. Two gel formulations were prepared using HPMC and chitosan as the polymeric base. Their physicochemical properties (pH, viscosity, spreadability), rheological behavior, mucoadhesive strength, in vitro drug release, antimicrobial activity against Staphylococcus aureus and Escherichia coli, and six-week stability were evaluated using validated protocols. Drug release kinetics were modeled using Korsmeyer–Peppas and Higuchi equations. Both gels exhibited pseudoplastic rheology and remained stable throughout storage. The HPMC gel had lower viscosity and greater spreadability, resulting in faster drug release. The chitosan gel demonstrated significantly stronger mucoadhesive strength and sustained drug release over 8 hours. Antimicrobial activity was comparable between formulations. No significant changes in pH or viscosity were observed during the stability period. Both polymers are suitable for CHX gel formulation, with HPMC offering ease of application and rapid release, while chitosan provides superior mucoadhesion and prolonged release. These findings support further in vivo evaluation and highlight the potential of polymer-based CHX gels as improved alternatives to traditional mouthwashes in oral infection management.
AI-Driven Discovery of Syringic Acid as an Anthelmintic Agent: Integrating PySCF-Based DFT, Molecular Dynamics, and In Vitro Validation Targeting β-Tubulin
Helminthiasis is a global health issue that is particularly prevalent in developing countries. Current anthelmintic drugs, mainly benzimidazoles, have side effects and are resistant to parasites. This study investigated the anthelmintic activity of syringic acid (SYR), a natural polyphenolic compound, against Pheretima posthuma, which targets β-tubulin, using both in silico and in vitro approaches. Drug likeness and ADME/T showed that SYR has a better pharmacokinetic profile than albendazole (ALB). Density functional theory calculations provided insight into the electronic properties and reactivity of SYR and ALB. Molecular docking studies revealed that SYR has a strong binding affinity (ΔG = -6.3 kcal/mol) for β-tubulin, similar to that of ALB (ΔG = -7.2 kcal/mol). Molecular dynamics simulations confirmed the stable binding of SYR in the β-tubulin active site for 100 ns. An in vitro anthelmintic assay on Pheretima posthuma demonstrated that SYR exhibits dose-dependent activity in inducing paralysis and mortality, but is less potent than ALB. The consistency between the computational predictions and empirical bioactivity assays provided preliminary evidence that SYR is a genuine anthelmintic agent. However, further in vivo studies are needed to evaluate the pharmacodynamics, safety, and immunological effects of SYR in complex biological systems before clinical trials. This study provides a basis for the development of new, safer, and more effective anthelmintic agents that target β-tubulin, addressing the problems associated with drug resistance and the side effects of current treatments.
Nootropic Effects of Neolamarckia cadamba Leaves on Scopolamine-Induced Amnesia in Rats
This study evaluated the memory-enhancing potential of Neolamarckia cadamba (Roxb.) Bosser ethanolic extract (200 and 400 mg/kg, orally) in scopolamine-induced amnesic rats, with piracetam as a standard. Cognitive function was assessed using the elevated plus maze, hole board test, and Morris water maze, along with locomotor activity and brain acetylcholinesterase (AChE) levels. Phytochemical analysis revealed 0.515 g% phenolics (gallic acid equivalents) and 2.129 g% flavonoids (quercetin equivalents). GC–MS profiling identified 11 major bioactive compounds with reported antioxidant, anti-inflammatory, and neuroprotective activities. In vitro antioxidant evaluation by the DPPH assay demonstrated concentration-dependent radical scavenging, with an IC₅₀ of 337.42 µg/mL. Oral administration of N. cadamba extract for 14 days significantly reversed scopolamine-induced memory deficits. The extract reduced transfer latency in the elevated plus maze, shortened escape latency in the Morris water maze, and increased exploratory behavior in the hole board test. It also enhanced locomotor activity and decreased AChE levels, indicating improved cholinergic function. The high dose (400 mg/kg) consistently produced superior effects, suggesting dose-dependent efficacy. These findings suggest that N. cadamba ethanolic extract exhibits nootropic and neuroprotective effects, likely through antioxidant and cholinergic mechanisms, and may be a promising candidate for managing cognitive impairments, including Alzheimer’s disease.
Assessment of Antidepressant Activity of Phosphodiesterase-4 Inhibitor Drotaverine in Swiss Albino Mice
Depression is a mental health disorder characterized by profound feelings of sadness and a sense of hopelessness. It is a life-threatening disorder and approximately 20% of world’s population is affected by depression. Drotaverine is used as an anti-spasmodic drug. It is structurally like Papaverine. It selectively inhibits the phosphodiesterase-4 (PDE-4) enzyme. The antispasmodic medication drotaverine was utilized as a test drug in this investigation, and its effects as an antidepressant were examined. Compared to the standard drug imipramine used for depression therapy, it has fewer negative effects. For a variety of behavioral (in vivo) and non-behavioral (in vitro) investigations, we have employed Swiss Albino mice. The Forced Swim Test, Tail Suspension Test, and Elevated Plus Maze Model Test are three behavioral models that were applied to estimate the antidepressant influence of drugs. The non-behavioral techniques of MAO-A and MAO-B inhibition were employed to assess the antidepressant action of medications. We have also conducted an antioxidant investigation using the Nitric Oxide Scavenging Assay and Glutathione (GSH) estimate. Additionally, histopathological investigations and protein measurements were carried out. The outcomes were noteworthy and excellent. The test drug has shown considerable efficacy and promise as an antidepressant agent in the Tail Suspension Test (TST) (*p<0.05), Elevated Plus Maze Model Test (EPM) (*p<0.05), as well as Forced Swim Test (FST) (*p<0.01). The results were compared to the reference drug. The test medication had little to no effect on MAO inhibition, in accordance with assessment of MAO-A alongwith MAO-B. Nitric oxide (*p<0.05), glutathione (GSH) estimation (****p<0.0001), and total protein estimation (****p<0.0001) all showed considerable scavenging effects. The histopathological results provided a quick overview of the effects of both experimental and prescription medications, as well as the alterations to the cerebellar granular neurons, Purkinje cells, and cerebrum cell bodies. This points to the drug's protective function in the brain.
In Vitro Evaluation of Nanoemulsion of Gotu Kola Leaves (Centella Asiatica Urb.) as an Alternative Treatment for Tuberculosis
Gotu kola leaves (Centella asiatica Urb.) contain asiaticoside compounds that have been demonstrated to possess bactericidal properties against Mycobacterium tuberculosis (M. tuberculosis), as evidenced by inhibition tests. Several studies have reported that M. tuberculosis has developed resistance to tuberculosis (TB) drugs. The nanoemulsion delivery system represents an innovative therapeutic approach for TB patients, demonstrating significant promise in the diagnosis, treatment, and prevention of infectious diseases such as TB. This study aims to optimize and formulate the manufacture of a gotu kola leaf extract nanoemulsion as an alternative TB treatment. Maceration was employed to obtain a gotu kola leaf extract, yielding 34.7%. Thin-layer chromatography (TLC) analysis revealed a single spot, confirming the presence of asiaticoside. A gotu kola leaf nanoemulsion was developed using the Box-Behnken Design method, incorporating variations in gotu kola leaf extract loading, tween 80, and sonication time. The optimal formula was determined based on particle size parameters, particle size distribution, entrapment efficiency (EE), and extract loading (EL) using Stat-Ease® Design-Expert 360 software. The writing has been corrected. The optimal formula exhibited a particle size of 154.715 nm, a particle size distribution of 0.246, an EE of 92.512%, and an EL of 98.298 mg/g. In vitro testing demonstrated the antibacterial potential of the optimum formula, achieving a 56.2% antibacterial effect. In contrast, the positive control rifampicin showed an 89.1% antibacterial effect.
The Role of Aryl Hydrocarbon Receptor in Proliferation and EMT Induction in Neuroblastoma Cancer Cells (SH-SY5Y)
Neuroblastoma is a common and aggressive cancer in children characterized by metastasis and uncontrolled cell proliferation. The Aryl Hydrocarbon Receptor (AhR) is a crucial regulator of diverse biological processes, such as cell growth, immune responses, and metabolism. However, its role in neuroblastoma progression is inadequately investigated. SH-SY5Y neuroblastoma cells were treated with the AhR antagonist CH223191, the agonist benzo[a]pyrene (BaP), and the endogenous ligand 6-Formylindolo[3,2-b]carbazole (FICZ). Cell viability was evaluated by MTT assay, and ROS levels were measured by dichlorofluorescein (DCF) assay, while EMT-related gene expression (vimentin and E-cadherin) was analyzed using qPCR. Compared to control, treatment with CH223191 and BaP significantly decreased cell viability and increased ROS production, respectively. BaP induced a greater reduction in viability and increase in ROS than FICZ (p < 0.01). Gene expression analysis revealed that CH223191 and BaP decreased vimentin expression (p < 0.05 and p < 0.001) and increased E-cadherin expression (p < 0.05 and p < 0.001), indicating the inhibition of EMT and promotion of epithelial characteristics. These findings highlight the pivotal role of AhR in modulating proliferation, mitochondrial function, and EMT in neuroblastoma cells, indicating that targeting AhR signaling may offer a novel therapeutic strategy to impede neuroblastoma progression and metastasis.
Chenopodium botrys extract: The preventive effects on the hepatotoxicity induced by Adriamycin
Adriamycin, as a drug, is known to induce hepatotoxicity at high doses. This study investigated the preventive effect of Chenopodium botrys extract on Adriamycin-induced liver damage in rats. Twenty-four rats were randomly divided into control, Adriamycin, and prevention groups, including the extract of Chenopodium botrys combined with Adriamycin and silymarin combined with Adriamycin. The experimental period was 30 days. Ultimately, blood was drawn, and liver tissue was removed for evaluation of oxidation markers and biochemical analysis. Administration of Chenopodium botrys significantly decreased the biochemical parameters related to liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), compared to the Adriamycin group. Oxidative parameters, including total thiol content, superoxide dismutase (SOD), and catalase, were improved in the preventive groups compared to Adriamycin in liver tissues. The data confirm that Adriamycin induces hepatic oxidative stress and liver damage. At the same time, co-treatment with the Chenopodium botrys effectively attenuates these adverse effects by restoring redox balance and preserving liver integrity. These findings highlight the therapeutic potential of natural antioxidants in preventing Adriamycin-induced hepatotoxicity.
Comparison of Taurine and Metformin on Paraoxonase Enzyme Activity and Lipid Profiles in Streptozotocin-Induced Diabetic Rats
Diabetes remains a pressing global health challenge, demanding innovative biochemical interventions for effective management. This study evaluates the effects of taurine and metformin on glucose regulation, lipid metabolism, and antioxidant enzyme activity in diabetic rats. Diabetes was induced in mice using a single intraperitoneal dose of streptozotocin (60 mg/kg), and animals with blood glucose levels exceeding 300 mg/dL were considered diabetic. The experimental subjects were systematically classified into four groups: healthy controls, diabetic controls, metformin-treated diabetics, and taurine-treated diabetics. Metformin and taurine were each administered via oral gavage at a dosage of 500 mg/kg/day for a period of one month, beginning seven days post-diabetes induction. Key indicators assessed included changes in body weight, fasting glucose levels, serum lipid components, and paraoxonase enzymatic activity. Metabolic evaluations included fasting blood glucose, body weight, lipid profile parameters, and paraoxonase enzyme activity. Metformin treatment did not significantly alter weight relative to the diabetic group, whereas taurine led to a notable improvement. Hyperglycemia was markedly reduced in both treatment groups compared to diabetic controls. Furthermore, analysis of lipid components revealed significant normalization: triglyceride, cholesterol, and LDL levels decreased, while HDL concentrations increased with both interventions. Antioxidant assessment showed restored paraoxonase activity in taurine- and metformin-treated animals. These outcomes support the hypothesis that taurine and metformin contribute to the restoration of biochemical equilibrium in diabetic conditions. Both Taurine and metformin can modulate Diabetes-related metabolic disturbances, aiding in physiological stabilization. Both agents promoted glycemic correction, lipid improvement, and enzymatic recovery. Their efficacy suggests promise in supportive metabolic care for diabetes.
Phytochemical Characterization and Skin Cancer Inhibitory Potential of Ficus hispida Methanolic Extract: Insights from Molecular Docking and Cell-Based Assays
This study investigates the anticancer potential of Ficus hispida fruit extract, focusing on its phytochemical composition and molecular interactions with skin cancer targets. Fruits were collected from Jamia Salafiya Pharmacy College, and 500 g were subjected to Soxhlet extraction using methanol, yielding a concentrated ethyl acetate extract. LC-MS/MS analysis identified key bioactive compounds, including quercetin (m/z 302.33), kaempferol (m/z 284.26), gallic acid (m/z 169.14), lupeol (m/z 434.48), and β-sitosterol (m/z 414.58), confirming the extract's chemical diversity. In-silico molecular docking showed that gallic acid exhibited notable binding affinities with skin cancer-related proteins: 1M17 (-6.3 kcal/mol), 4QTB (-5.4 kcal/mol), and 5MP8 (-5.6 kcal/mol). Hydrogen bonding, van der Waals interactions, and π-alkyl interactions were observed, particularly with residues Asp831, Arg-84, and Asn118, indicating the formation of stable ligand-protein complexes. Molecular dynamics (MD) simulations further validated stability, with low RMSD (2.0 Å) and compact radius of gyration (19.8 Å). MM-GBSA binding free energy analysis yielded a favorableΔG_bind of -58.61 kcal/mol for the gallic acid-1P7K complex. In vitro MTT assays revealed dose-dependent cytotoxicity of gallic acid against SKML skin cancer cells, with an IC50 value of 13.601±0.488 µg/mL. AO/EB staining confirmed effective induction of apoptosis in treated cells. These results collectively highlight the effectiveness of gallic acid from Ficus hispida as a promising candidate for skin cancer therapy, warranting further preclinical and clinical investigations for therapeutic development.
Antibacterial potentials of Rothmannia octomera (Rubiaceae) root extracts on a few bacterial etiologies of respiratory tract infections
Rothmannia octomera is a plant of the Rubiaceae family used in traditional medicine to treat bronchopulmonary infections. To contribute to the valorization initiatives of this plant, we undertook a study of its root phytochemistry. We assessed its antibacterial potential against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus, which are considered bacterial etiologies of respiratory infections. The phytochemical screening of the hydroethanolic (30:70 v/v) and CH2Cl2/MeOH (50:50 v/v) extracts of Rothmannia octomera, obtained by maceration, was carried out using colorimetric and precipitation tests for several groups of secondary metabolites. For the antibacterial potential of the extracts, minimal inhibitory and bactericidal concentrations (MICs and MBCs) were determined by macrodilution in a liquid medium. Results revealed the presence of phenols, tannins, flavonoids, sterols, anthraquinones, and saponins in both extracts. MIC values for the hydroethanolic extract ranged from 12.5 to 200 mg/mL, while MBC values varied from 50 to 400 mg/mL. For the CH2Cl2/MeOH extract, the MIC values recorded ranged from 50 to 200 mg/mL, and the related BMCs ranged from 100 to 200 mg/mL. The BMCs/MICs ratios revealed a bactericidal effect of the hydroethanolic extract on Pseudomonas aeruginosa and Klebsiella pneumoniae, as well as a bacteriostatic potential on Staphylococcus aureus. With the CH2Cl2/MeOH extract, bactericidal action was observed against all the bacteria tested. This study justifies, for the first time, at least in part, the use of Rothmannia octomera in traditional medicine. Indeed, investigations on the safety of this plant and dosages required for its optimal use in disease control are necessary.
Potential Therapeutic Role of N-acetylcysteine Against Risperidone-Induced Oxidative Stress in Caenorhabditis elegans
Risperidone, an antipsychotic drug, is widely used for treating mental health disorders such as schizophrenia, psychosis, etc. Despite its therapeutic benefits, Risperidone has been linked to oxidative stress through several pathways, including increased lipid peroxidation, mitochondrial and lysosomal dysfunction, excessive production of reactive oxygen species (ROS), and depletion of intracellular antioxidants such as glutathione (GSH). These changes impair membrane integrity, disrupt cellular redox balance, and increase the cytotoxic consequences. To address this, the current study examined how N-acetylcysteine (NAC), a potent thiol antioxidant and glutathione precursor, protects against oxidative damage induced by Risperidone. We assessed oxidative stress indicators such as ROS, lipid peroxidation (MDA), antioxidant enzyme activities (GSH, SOD, CAT), and oxidative stress tolerance (tBHP assay) using Caenorhabditis elegans as a model organism. Results showed decreased worm survival, increased oxidative stress markers, and compromised antioxidant defences with 50 μM risperidone exposure. However, pretreatment with 10 mM NAC effectively reduced ROS levels, enhanced GSH, and reduced lipid peroxidation, thereby improving survival under oxidative stress conditions (tBHP assay), which supports its role in maintaining redox balance. These findings suggest that risperidone-induced toxicity is mediated through oxidative stress, and NAC may offer a protective effect, presenting a potential therapeutic approach to mitigate its damaging effects.
Nephroprotective Power of Allium ampeloprasum Subsp. Iranicum: Attenuating Cyclophosphamide-Induced Kidney Injury through Antioxidant and Anti-Inflammatory Mechanisms
The kidneys are essential organs that perform key functions for maintaining homeostasis. Cyclophosphamide (CP), a widely used chemotherapy agent, can cause nephrotoxicity through multiple mechanisms driven by oxidative stress. Allium ampeloprasum subsp. Iranicum, known for its antioxidant and anti-inflammatory properties, contains bioactive compounds that may mitigate these adverse effects. The study aims to determine whether the antioxidant properties of A. ampeloprasum can help maintain kidney function and enhance the effectiveness of treatment during CP therapy. Mice were divided into four groups: negative control, A. ampeloprasum only (150 mg/kg), CP-treated (20 mg/kg), and combined A. ampeloprasum (150 mg/kg) with CP (20 mg/kg). Treatments were administered both orally and intraperitoneally over 14 days. Blood and tissue samples were analyzed for biochemical, histopathological, and molecular markers, including lipid peroxidation, antioxidant enzymes, and inflammatory cytokines. The data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test for multiple comparisons. CP treatment resulted in significant weight loss, tissue inflammation, and structural kidney damage, along with elevated serum markers of kidney injury, increased lipid peroxidation, and decreased antioxidant enzyme activities. Histopathological analysis confirmed inflammatory changes and tissue disruption caused by CP, which were significantly mitigated by pretreatment with A. ampeloprasum extract. This extract reduced serum levels of urea, creatinine, and uric acid, and decreased lipid peroxidation in tissues. It boosted antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Additionally, A. ampeloprasum pretreatment markedly reduced levels of inflammatory cytokines compared with CP alone. This study demonstrates that A. ampeloprasum extract effectively mitigates CP-induced toxicity by reducing oxidative stress, inflammation, and tissue damage, indicating its potential as a natural protective agent during chemotherapy.
Formulation, Development, Characterization, and Cytotoxicity Study of Dasatinib Monohydrate Loaded Solid Self-Nano Emulsifying Drug Delivery System (SNEDDS) for Enhancement of Solubility and Oral Bioavailability
To improve the dissolution and solubility of dasatinib monohydrate (DAS), this study aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS). Syloid 244FP was utilized as a solid carrier in this study to formulate and further develop liquid SNEDDS (L-SNEDDS) containing dasatinib monohydrate into a solid form. Based on the findings of the initial screening, nine batches of DAS-loaded SNEDDS were prepared using Tween 20, PEG 400, and Capryol 90 as surfactant, cosurfactant, and oil, respectively. Ternary phase diagrams were created for the chosen systems to determine the nanoemulsification region. The study demonstrates that the average globule size of the optimized batch of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) fell within the nanometric scale, with optimal Polydispersity Index (PDI) values. All batches also demonstrated rapid emulsification time, high drug loading efficiency, and good optical clarity. The development of uniform, spherical droplets smaller than 100 nm was demonstrated by TEM analysis. Over 90% of the DAS was released in about 120 minutes, according to in vitro DAS release from SNEDDS formulae. The optimized SNEDDS formulation was selected for conversion into solid SNEDDS (S-SNEDDS) using suitable solid carriers. The synthesized S-SNEDDS formulae were assessed for drug content, cytotoxicity, FTIR, in vitro dissolution, and micromeritic properties. It was discovered that S-SNEDDS formulations exhibited excellent flow characteristics, significant drug release, and elevated drug content. The MTT assay results indicate that DAS-S-SNEDDS exhibits a dose-dependent cytotoxic effect against the HL60 (Human Leukemia) cell line. Compared with standard cytotoxic agents, DAS-S-SNEDDS exhibits a significant, potent effect against the HL60 (Human Leukemia) cell line. In vitro drug release studies demonstrated a marked enhancement in the dissolution rate of DAS. These findings indicate that DAS-S-SNEDDS may serve as an effective strategy to enhance the oral bioavailability and solubility of DAS.
Design of Experiment-Based Optimization in Formulation of Atorvastatin Solid Dispersion using Linum usitatissimum Seed Gum
Solid dispersion (SD) is the most promising approach for enriching the drug release of poorly soluble drugs. Atorvastatin (ATR) is a lipid-lowering drug, but its low water solubility hinders its dissolution and effective treatment. In this study, flaxseed gum (FSG) derived from Linum usitatissimum has been investigated as a potential carrier for SD formulations to overcome solubility limitations. A modified hot extraction procedure was employed to isolate FSG, which was subsequently characterised for its physical properties. Design of experiments was conducted using Response Surface Methodology (RSM), with FSG concentration, solvent volume, and temperature as independent variables to optimize the SD formulation via the solvent evaporation technique (SEV). In contrast, the percentage of drug release in 30 minutes serves as the response variable. The formulations were assessed for product quality parameters, and the optimized SD formulation was characterized physicochemically. 33.8 mg of FSG, 8 mL of solvent (ethanol), and 42.5°C were identified as critical quality attributes through RSM. The optimized ATR-SDs formulation exhibited 92% drug release in 30 minutes, 98% drug content, and 1.53-fold improved solubility than pure ATS. Differential scanning calorimetry and x-ray diffraction analysis showed that the drug crystalline form transformed to an amorphous state, while scanning electron microscopy images revealed increased porosity in SD. The current research has demonstrated that the SD of ATR employing a natural carrier could be a promising formulation for enhancing solubility and dissolution.
Fabrication and Characterization of Soframycin-Loaded Carboxymethyl Tamarind Gum-Guar Gum Hydrogel Films
Hydrogel films fabricated solely from citric acid (CA)-crosslinked carboxymethyl tamarind gum (CMTG) often suffer from poor matrix integrity and limited swelling capacity, hindering their practical utility in drug delivery and other biomedical applications. To address these challenges, this study developed hydrogel films by blending CMTG with guar gum (GG) and crosslinking with citric acid, aiming to enhance the films' matrix integrity and swelling behavior substantially. The hydrogel films were loaded with soframycin via diffusion. The fabricated films were evaluated for various parameters, including weight loss, thickness, total carboxyl content, wettability, permeability, protein adsorption, and hemocompatibility. The swellability of the films was studied in Tris-HCl buffer (pH 7.4) and 0.1 N HCl. In addition, drug release studies were conducted in Tris-HCl buffer (pH 7.4). The films were characterized using ATR-FTIR spectroscopy and thermal analysis. The findings revealed that the concentrations of GG and CA affected the weight loss, thickness, total carboxyl content, and contact angle. The swelling of CMTG-GG hydrogel films was found to be greater than that of previously reported CMTG-PVA films. The fabricated films exhibited optimum water vapor transmission and microbial impermeability. Protein adsorption on the hydrogel films remained minimal. Additionally, the hemolysis percentage remained below the accepted limit of 5 %, confirming that the hydrogel films were compatible with blood. The ATR-FTIR analysis confirmed the crosslinking. The drug release from the soframycin-loaded hydrogel films was found to be 39.1 % to 79.69 % at the end of 6 h. The drug release from these hydrogel films followed a non-Fickian diffusion mechanism. These findings suggest that hydrogel films composed of CMTG and GG have promising potential for drug delivery.
Design, Optimization, and Characterization of Tranexamic Acid Microemulsion for Topical Delivery
This study focuses on the design, optimization, and evaluation of tranexamic acid (TXA) microemulsions (ME-TXA) for topical delivery to manage melasma. TXA is an antifibrinolytic agent that competitively inhibits plasminogen activation and acts as a non-competitive plasmin inhibitor, reducing melanin synthesis and inflammation in pigment cells. Beyond melasma, TXA has demonstrated potential for treating various skin disorders, including post-inflammatory hyperpigmentation, melanin-related pigmentation disorders [1], and chronic inflammatory conditions such as atopic dermatitis and rosacea [2]. Studies suggest that TXA can be beneficial in treating melasma [3]. The microemulsions were formulated using Labrafac PG/Transcutol P as the oil phase, Tween 80 and Span 80 as surfactants, and propylene glycol (PG) (10:1 ratio) as a co-surfactant These systems offer advantages such as improved drug solubility, enhanced skin penetration, controlled release, and increased formulation stability, making them ideal for topical delivery of TXA [4]. Physicochemical properties, including particle size, viscosity, zeta potential, and permeability, were systematically analyzed. Characterization of the formulations demonstrated particle sizes ranging from 15.08 to 34.75 nm, viscosities between 147.83 and 300.3 cps, and zeta potentials from -1.7 to -13.2 mV, ensuring stability and homogeneity. In vitro release studies indicated a cumulative drug release of up to 99.3% over 24 hours, following first-order release kinetics. The optimized formulation demonstrated enhanced TXA solubility, stability, and controlled drug release compared to aqueous solutions. Skin permeation studies revealed significantly enhanced drug permeation, with the optimized formulation achieving a steady-state flux (Jss) of 5.544 mg/cm²·h and a permeability coefficient (P) of 0.1108 cm/h. In addition, the apparent diffusion coefficient (Dapp) analysis demonstrated a reduced lag time (Tlag) compared to aqueous TXA.” These findings highlight the potential of ME-TXA as a biocompatible and efficient drug delivery system, offering improved solubility, stability, controlled release, and enhanced transdermal permeability for the effective management of melasma.
In-Silico and In-Vivo Evaluation of Luteolin and Imeglimin as Novel Therapeutic Agents in Reserpine-Induced Parkinsons Disease in Rats
Parkinson's disease (PD) is the second most prevalent late-life movement disorder, characterized as a hypokinetic condition involving selective and extensive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the striatum. This study investigated the neuroprotective effects of luteolin and imeglimin against reserpine-induced PD in rats, focusing on the dopamine transporter protein (DAT), α-synuclein aggregation, and proinflammatory cytokines using both in silico and in vivo approaches. In- silico molecular docking studies were followed by in vivo experiments. PD was induced in rats by administration of reserpine (1 mg/kg, s.c.) every other day for 3 days. Pretreatment with luteolin (50 mg/kg, p.o.) and imeglimin (100 mg/kg, p.o.) was given for 5 days. Behavioral assessments (orofacial dyskinesia, catalepsy, and rotarod) were performed on day 5, followed by biochemical and histopathological evaluations. Parameters measured included oxidative stress markers (CAT, GSH, SOD, and LPO), neurotransmitters (dopamine and nitric oxide), proinflammatory cytokines (TNF-α and IL-1β), and α-synuclein expression. Reserpine-treated rats exhibited increased catalepsy duration, orofacial dyskinesia (tongue protrusions, vacuous chewing), and impaired motor coordination. Biochemical analysis showed reduced antioxidant levels (CAT, GSH, SOD), reduced dopamine levels, and elevated LPO, TNF-α, IL-1β, and α-synuclein. Combined treatment with luteolin and imeglimin significantly mitigated these behavioral and biochemical alterations—improving locomotor activity, reducing dyskinesia, and normalizing antioxidant and inflammatory markers. Dopamine levels were restored, and α-synuclein aggregation was notably reduced. Histopathology confirmed dopaminergic neuronal preservation and reduced Lewy body formation in the treatment group. These findings suggested that luteolin and imeglimin, particularly in combination, offer neuroprotective effects in PD by reducing oxidative stress, inflammation, and α-synuclein aggregation, thereby preserving dopaminergic neurons and brain function.
From Innovation to Profit: Exploring the Relationship between Research Activities and Economic Performance in Iran’s Pharmaceutical Industry using System Dynamics
Iran’s pharmaceutical industry faces challenges such as low returns on R&D, lack of market exclusivity, and strict pricing regulations, which limit profitability and reduce incentives for innovation. Addressing these issues requires a strategic approach to managing the entire drug development cycle, balancing research and marketing efforts to drive sustainable growth. This study uses system dynamics modeling to evaluate the financial outcomes of pharmaceutical R&D activities in Iran. Through a comprehensive literature review and Delphi method, twelve key indicators related to R&D and marketing were identified. These indicators informed a validated system dynamics model developed in Vensim PLE, simulating company performance over 25 years. Results show that profits positively reinforce research activities, creating a feedback loop that supports growth in profitable products and intangible assets. Sensitivity analysis highlights the importance of business size and cash cow products in financial performance. While marketing boosts short-term sales and product profitability, long-term success relies on sustained R&D investment. Excessive marketing without innovation yields diminishing returns, whereas combined investment in R&D and marketing produces synergistic effects, significantly increasing sales and new product development. In conclusion, integrated strategies aligning R&D and marketing efforts are essential for fostering innovation-led growth and improving financial sustainability in Iran’s pharmaceutical industry.
Synthesis, characterization, and antibacterial evaluation of silver oxide nanoparticles (AgONPs) using terephthalic acid
Recently, silver oxide nanoparticles (AgONPs) have come into the spotlight as promising options for cancer treatment. Their popularity stems primarily from their unique physical and chemical properties and their potential as effective anticancer agents. This study examines how these nanoparticles are made from terephthalic acid and then calcined at 600°C. After they are created, these nanoparticles are carefully examined to determine how they exhibit antibacterial activity. To fully understand these nanoparticles, several advanced analytical techniques are being used. These methods include X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), Dynamic Light Scattering (DLS), and zeta potential analysis. The results show that the AgONPs are mostly cubic, with an average size of 171.34 nm and a slightly negative zeta potential. Lab tests suggest that these nanoparticles exhibit strong antibacterial activity against Gram-negative and Gram-positive bacteria.