Advances in Pharmacological and Pharmaceutical Sciences最新文献

Type II diabetes remains a significant global public health issue, affecting both individual well-being and healthcare systems worldwide. Metformin hydrochloride is widely prescribed as the first-line treatment for managing diabetes. However, the increasing reports of substandard and falsified medicines, including metformin, circulating in the markets in recent years, highlights the urgent need for reliable and portable quality assurance tools. Thin-layer chromatography (TLC) has long been extensively used as a screening method to verify the identity and quality of various medicines. In this work, we present a smartphone-assisted TLC method for quantitative analysis of metformin hydrochloride. The TLC was performed using silica gel 60 F₂₅₄ plates as the stationary phase and acetic acid-methanol-water 0.25:7:4 (v/v) as a mobile phase. We used a custom-made UV-illuminated TLC imaging box to capture images via smartphone and images were analyzed using a custom written smartphone application to calculate the R _f and the concentration of metformin in the principal TLC spots. The smartphone application, TLC Analyzer, accurately calculated the R _f values (0.604) consistent with those obtained using ImageJ software. The linearity of the method was 0.5-4 mg/mL. After optimization, the TLC Analyzer method was used to analyze metformin samples (n = 16) collected from local pharmacies. The results were compared with those from ImageJ analysis, UV-Vis spectrophotometry, and HPLC. The smartphone-based TLC Analyzer method identified 15 of the 16 samples as containing acceptable levels of metformin in accordance with pharmacopeial standards, consistent with ImageJ and spectrophotometric results. In contrast, the HPLC method indicated that all 16 samples met the pharmacopeial criteria.

Adalimumab, marketed as Humira, is a fully humanized monoclonal antibody that blocks the activity of tumor necrosis factor-alpha and is used in treating several autoimmune disorders. As one of the top-grossing pharmaceuticals, its global sales surpassed $20 billion in 2023, leading to significant biosimilar development, with 10 products available by 2025. This review analyses published preclinical studies to assess the evaluation methods employed to establish biosimilarity between Humira and four key biosimilars: ABP501 (Amjevita), FKB327 (Hulio), MSB11022 (Idacio), and SB5 (Imraldi). Our comparative analysis reveals that primary structure, glycosylation profiles, Fc receptor binding affinity, and TNF-alpha neutralization potency are critical quality attributes essential for establishing biosimilarity. Notably, while all four biosimilars demonstrated comparable functional properties to the reference product, variations in glycosylation patterns presented distinct regulatory challenges. This review is a valuable resource for biopharmaceutical scientists engaged in biosimilar development, ultimately supporting advancing more accessible and affordable treatment options while ensuring adherence to stringent efficacy, safety, and quality standards of adalimumab biosimilars.

Purpose: This cross-sectional study assessed determinants of benzodiazepine (BZP)-dispensing practices among community pharmacy dispensers in Dar es Salaam, Tanzania. Methods: A cross-sectional study involving 378 community pharmacy dispensers was conducted between March and June 2024. An adapted structured questionnaire was used to gather information on the sociodemographics, most dispensed BZPs, dispensers' knowledge, and dispensing practice of BZPs. Determinants of dispensing practice were determined by multivariable logistic regression analysis using SPSS Version 23. Results: Of 378 dispensers, 232 (61.4%) were female, 263 (69.6%) had a college education level, and 193 (51.1%) were pharmaceutical technicians. Diazepam was the most dispensed BZP (163 (43%)), followed by lorazepam (102 (27%)). More than half, 203 (53.7%), of the dispensers had inadequate knowledge, and 240 (63.5%) of dispensers had good dispensing practices. Nonpharmaceutical dispensers were less likely to have good dispensing practice (AOR = 0.16, 95% CI (0.05-0.49)) whereas having adequate knowledge of BZPs (AOR = 2.64, 95% CI (1.64-4.25)) were significantly associated with the good dispensing practice of BZPs. Conclusion: Knowledge levels and the type of pharmaceutical professionals are determinants in ensuring proper BZP-dispensing practices. These indicate the need for continuous professional development and stricter enforcement of dispensing regulations to improve pharmacy practices and prevent unauthorized BZP dispensing.

Tacca chantrieri André is a native plant from Northern Thailand with reported pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. This study investigated the neuroinflammatory and cognitive-enhancing effects of Tacca chantrieri André rhizome extract (TCE) in a scopolamine-injected model, which mimics an Alzheimer's disease (AD) animal model. Animals were divided into six groups: (1) a control group, (2) a vehicle-treated group, (3) a donepezil-treated group (3 mg/kg BW) as a positive control, and (4-6) three TCE-treated groups receiving 50, 100, or 200 mg/kg BW once daily for 14 days. Starting on Day 8, animals received daily intraperitoneal injections of scopolamine (3 mg/kg BW) for 7 consecutive days to induce cognitive impairment. On day 14, behavioral tests were conducted, including the Y-maze and open field tests. On day 15, animals were euthanized, and their brains were collected for Nissl staining, immunofluorescence staining, and biochemical analyses using an ELISA kit. Our results demonstrated that TCE treatment attenuated scopolamine-induced memory deficits and neuroinflammation. Specifically, TCE administration reduced levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and decreased glial fibrillary acidic protein (GFAP) expression in the hippocampus. Additionally, TCE improved neuronal survival and enhanced serotonin levels, contributing to cognitive improvements. The qualitative analysis of TCE using LC-QTOF-MS identified various chemical constituents, including saponins, flavonoids, and phenolic compounds. These bioactive compounds contributed to the neuroprotective effects of TCE by modulating neuroinflammation and cognitive function. The neuroprotective effects of TCE suggested its potential as a therapeutic agent for memory impairment associated with AD.

The potential uses of extracting mucilage from plant sources have led to much research in this field. One possible source of mucilage for agri-food-pharma utilization is the fruits of the Phoenix dactylifera, date palm. For developing the plaster gel loaded with nicotine, we, therefore, applied the mucilage from date palm fruits as a gel-forming agent. Other components, however, might be added to increase its properties. Response surface methodology was used for quantifying the effects of a range of variables (date palm mucilage, PVA, and glycerin) on physicochemical parameters (pH value, viscosity, drying time, ultimate tensile strength, elongation at break, and drug content). The optimal formulation was 3.5%:1.8%:30% w/w. The resultants were 6.14 ± 0.05, 45.67 ± 1.75 cp, 14.77 ± 1.19 min, 26.83 ± 2.15 MPa, 38.20 ± 2.39%, and 9.51 ± 0.19 mg/g, respectively. The optimal formulation of nicotine-containing plaster gel had a semicrystalline structure as it was derived from plant mucilage. It was immediately obvious that the formulation might control the release of nicotine, indicating first-order kinetic release. The J _ss and K _p values were 0.30 ± 0.01 mg/cm²/h and 3.13 ± 0.11 × 10^-2 cm/h, respectively, indicating a maximum nicotine permeation of 78.82 ± 13.57%. When stored in a refrigerator as compared to room temperature, the nicotine-loading plaster gel thus showed excellent physical stability.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic frameworks, demonstrate enhanced targeting and therapeutic efficacy through HSP70 modulation. Functionalized nanocarriers exploit HSP70's tumour-specific overexpression to improve drug delivery, minimise off-target effects and overcome the blood-brain barrier. Emerging strategies such as chemophototherapy, immunotherapy and photothermal therapy leverage HSP70's interactions within the tumour microenvironment, enabling synergistic treatment modalities. The review also highlights translational challenges, including heterogeneity of GBM, regulatory hurdles and variability in the enhanced permeability and retention (EPR) effect. Integrating computational modelling, personalised approaches and adaptive trial designs is crucial for clinical translation. By bridging nanotechnology and molecular biology, HSP70-targeted strategies hold transformative potential to redefine GBM diagnosis and treatment, offering hope for improved survival and quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT00054041 and NCT04628806.

Our previous study has shown the beneficial effect of the ethanolic extract of Sangyod rice (SE) on lipid accumulation and insulin resistance. However, its effect on vascular inflammation has yet to be explored. The current study aimed to investigate the anti-inflammatory effects of SE in both in vitro and in vivo models, specifically examining its impact on LPS-induced inflammation in RAW264.7 cells and evaluating its efficacy in an animal model of diabetes mellitus induced by a high-fat diet combined with a low-dose streptozotocin. In the in vitro experiments, SE treatment effectively suppressed the LPS-induced activation of key signaling pathways, including Akt, ERK1/2, p38 MAPK, and NF-κB, which are known to play pivotal roles in the inflammatory response. SE was also found to reduce oxidative stress and the production of inflammatory markers in the LPS-stimulated RAW264.7 cells. In the in vivo experiments, the administration of SE (500 mg/kg BW) and metformin (200 mg/kg BW) to high-fat diet/streptozotocin-induced diabetic rats effectively improved dyslipidemia, as evidenced by reductions in serum total cholesterol, LDL-cholesterol, and triglycerides compared to the untreated diabetic control group. Importantly, SE ameliorated the damage to the vascular endothelium and elastic fibers by downregulating the expression of proinflammatory cytokines and oxidative stress markers. Additionally, SE administration attenuated the upregulation of key markers associated with ER stress-mediated apoptotic pathways, with effects comparable to those observed in diabetic rats treated with the standard antidiabetic drug metformin. These findings suggest that SE possesses both anti-inflammatory and vascular protective properties, evident in both in vitro and in vivo studies.

Bleomycin, an antibacterial antibiotic, is used in chemotherapy and is effective against various forms of human carcinomas. However, its use is limited due to its tendency to cause pulmonary fibrosis. Oxidative stress and excessive expression of TGF beta occur in pulmonary fibrosis, leading to cellular death, inflammation, and additional damage to lung tissue. Metformin has the ability to reduce oxidative stress and lower the level of TGF beta by activating AMPK. Additionally, ascorbic acid possesses potent antioxidant characteristics. Consequently, we decided to investigate the effects of these two medications on pulmonary fibrosis and compare with methyl prednisolone. Thirty-six adult mice were categorized into 6 distinct groups: Control, bleomycin (bleo), bleo + methyl prednisolone, bleo + metformin, bleo + ascorbic acid, bleo + metformin + ascorbic acid. Pulmonary fibrosis was induced by the administration of bleomycin in all groups, except for the control group. Subsequently, medications were administered for a duration of 14 days. Ultimately, the mice were sacrificed and lung tissues were obtained for biochemical and histological examination. As shown by biochemical and histological analysis, all treatment groups showed a decrease in oxidative stress factors, inflammation, and lung tissue fibrosis; however, the effects of administering metformin and ascorbic acid together were noticeable. Our study found that administering metformin and ascorbic acid over a period of 14 days, either alone or in combination, may contribute to the repair of pulmonary fibrosis. However, our data indicate that the combined therapy of these drugs provided a better result.

Alzheimer's disease (AD) is a neurological condition that causes neurons and axons in the brain to deteriorate over time and in a specific pattern. The enzyme beta-secretase-1 (BACE-1) plays a crucial role in the onset and progression of AD. In silico approaches, or computer-aided drug design, have become useful tools for reducing the number of therapeutic candidates that need to be evaluated in human clinical trials. Finding chemicals that bind to BACE-1's active site and inhibit its activity is key for preventing AD. A pharmacophore model was developed in this study based on potent BACE-1 inhibitors previously identified, and subsequently employed to screen a commercially available compound database for similar compounds. ZINC35883784 was identified with high binding affinities and hydrogen bonding interactions. Moreover, similar properties to donepezil were found in a compound made by altering the structure of ZINC35883784 called (4R,5R)-2-[1-(2-ethylcyclohexyl)ethyl]-4-hydroxy-5-(4-hydroxybutyl)cyclohexanolate (M4). Compounds were tested for interactions with BACE-1 and favorable properties. Binding scores were confirmed after molecular docking. The assessment of drug-likeness was conducted utilizing Swiss ADME analysis. Molecular dynamics simulations assessed the stability of compound interactions with BACE-1. MMPBSA calculated binding free energy and contribution energy. Results showed that M4 had strong and steady interactions with BACE-1. M4 was also analyzed by predicted NMR and retrosynthesis. However, further experiments are needed to evaluate M4's potential as a BACE-1 inhibitor.

Numerous therapeutic potentials of rutin (RUT) including cardioprotective, neuroprotective, and antihypertension activities have attracted many studies to bring it into clinical use. RUT is phytochemically derived from plants such as apples and tea. It is poorly soluble and very sensible to acidic pH in the stomach environment which leads to conceded oral bioavailability. In contrast, RUT is better soluble in basic environment, thus, encapsulating RUT within enteric microparticles (RUT-MP) using casein (CAS) resolved such problems. The encapsulation by spray-drying employed sugars (lactose, sucrose, and maltodextrin) as bulking agents and for stabilization of the amorphous drug. The developed RUT-MP formulations were prepared in two groups i.e., lower and higher RUT concentrations. The solid states were studied by X-ray diffraction (XRD), differential thermal analysis (DTA) and scanning electron microscopy (SEM). Solubility tests were also carried out on the samples to examine the outcome of the engineered physical modification. The results showed that the RUT-MPs were spherical in morphology. The RUT was transformed into amorphous structure as suggested by the XRD and DTA results indicating that RUT was molecularly dispersed in the RUT-MP. There were no phase separations that occurred as confirmed by the DTA data. Solubility tests carried out on the RUT-MPs showed that the encapsulation with CAS in group with higher concentration of RUT prevented the drug against recovery of the crystallinity and phase separations. The solubility test revealed various substantial enhancements of RUT solubility of the RUT-MPs at pH 7.0. The highest enhancement of RUT solubility was 191,5-fold, with respect to pure RUT. The presence of sugars was beneficial as they improved the yield percentage and might have contributed to the prevention of nano-crystal aggregation which made them a determining aspect for the successful application of spray-dried encapsulation.