Future Journal of Pharmaceutical Sciences最新文献

Background

Nebivolol hydrochloride (NBH) is a β-blocker known for its vasodilatory effects. According to the literature, it is commonly used to treat hypertension. Detecting drug molecules in bulk and tablet forms using statistical design is of significant importance in analytical science. Therefore, the objective of this work was to apply statistical experimental design principles to analyze NBH, utilizing a Box-Behnken design (BBD) to optimize the mobile phase composition.

Results

In this work, NBH was separated using an Inertsil ODS-3 V column with an optimized mobile phase consisting of 40:60% v/v acetonitrile (ACN) and 0.1% trifluoroacetic acid (TFA) in HPLC-grade Milli-Q water. The flow rate was programmed at 1 mL/min, and the column oven temperature was set at 40 °C ± 1 °C. Here, measurement was performed at 282 nm, with a retention time (Rt) of 5.41 min. Analysis of NBH in the marketed tablet formulation (Nebistar 10 mg) showed that the percentage of the labeled claim was consistent with the actual label claim. Additionally, the established method was validated in accordance with ICH guidelines.

Conclusion

The liquid chromatographic procedure developed is precise, accurate, and reliable, as indicated by %RSD values of less than 2%. As a result, it demonstrates significant potential for broad application in the analysis of NBH in both bulk and tablet formulations.

Graphical Abstract

Background

The non-sporting gym-goers are also turning to the use of performance-enhancing substances (PES) without medical guidance; according to recent statistics within the Middle East, there is also a rising pattern of abuse.

Methods

Following the escalating popularity of performance-enhancing substances among physically active groups, we conducted a cross-sectional survey of 300 gym users in Jordan between October 2023 and January 2024 via an Internet-based survey. The questionnaire, in a structured format, touched on sociodemographic factors, physical activities, knowledge, and information on performance-enhancing drugs, their actual use, and perceived negative health consequences. The statistical associations were tested using Fisher's exact tests, and multivariate logistic regression models were used to obtain adjusted odds ratios.

Results

Overall, 35.3% reported PES use. Use concentrated among males (48.9% of men vs 13.8% of women) and professional-level trainees (63.3% vs 19.7% of amateurs). Common products included protein and amino acids; 7.3% reported testosterone-based agents and 4.7% clenbuterol. Users more frequently reported heart palpitations and digestive complaints; the rate of any adverse event was 28.6% in users vs 6.2% in non-users. In adjusted models, male sex and professional training level remained strong predictors of PES use (AORs with 95% CIs reported in Table 1).

Conclusions

PES misuse is common in Jordanian gyms and clusters among higher-intensity male trainees, with non-medical information sources predominating. Findings support gym-linked pharmacist counseling, targeted education for high-risk groups, and stronger JFDA oversight in fitness settings.

Background

The low oral bioavailability of poorly water-soluble drugs poses a challenge during drug development. Fenofibrate has low aqueous solubility and poor oral absorption. The aim of the present work was to develop proliposome formulations of fenofibrate using lipid hydration and lyophilization techniques. The proliposome formulation was optimized by applying a 3² full factorial design by selecting the concentrations of phosphatidylcholine and cholesterol as independent variables and percent entrapment efficiency as the response variable. Tablet and capsule formulations of proliposomes were developed and compared with fenofibrate nanoparticulate tablets prepared by milling.

Results

The homogenized liposomal dispersion formulation (T8) and nanoparticulate tablet had final average median particle sizes (D50) of 151 nm, 148 nm and 224 nm, respectively. There was significantly less drug release from the proliposome formulations than from the nanoparticulate tablet, which exhibited complete drug release in 60 min. A pharmacokinetic study revealed that the proliposome-containing capsule formulation (T8-C) had greater bioavailability than did the proliposome tablet and nanoparticulate tablet.

Conclusion

The proliposome formulation was stable and could be developed into a solid dosage form, such as capsules, tablets, or powders, for oral suspension. Additionally, the proliposome formulation demonstrated greater absorption than the nanoparticulate fenofibrate tablet developed using wet milling/grinding technology.

Background

Acute cellular rejection (ACR) is a life-threatening event that mostly occurs in the first month after liver transplantation. Genetic polymorphisms in the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (NFKBIA) and protein tyrosine phosphatase non-receptor (PTPN22) genes are linked to organ rejection. Our study aimed to assess whether NFKBIA (rs696;126 G/A) and PTPN22 (rs2476601;1858G/A) gene polymorphisms are associated with ACR in liver transplant (LT) Egyptian recipients.

Methods

Our study was observational prospective cohort study. The study was conducted on LT Egyptian recipients on immunosuppression to investigate the influence of NFKBIA (rs696;126 G/A) and PTPN22 (rs2476601;1858G/A) gene polymorphism on the incidence of ACR after liver transplantation.

Results

Our study enrolled ninety-eight patients. Twenty-nine patients experienced ACR, while 69 patients showed no ACR. The homozygous allele (GG) of the PTPN22 (rs2476601;1858G/A) gene had lower rejection episodes when compared with heterozygous genotypes. Higher trough levels of tacrolimus and cyclosporin have shown a lower risk of ACR (p = 0.044 and p = 0.008), respectively.

Conclusion

Trough levels of immunosuppressant are not the only predictor for ACR but also genetic polymorphism plays a role.

Graphical abstract

Background

A new series of N-(3-(1H-indol-5-yl) phenyl) (5a–5j) derivatives and (4-(1H-indol-5-yl)piperazin-1-yl)(phenyl)methanone (9a–9j) derivatives was designed and synthesized to explore their potential anti-inflammatory, analgesic, and ulcerogenic activities using established in vivo models. To further elucidate the interaction mechanisms and predict binding affinities, molecular docking studies were conducted for all the synthesized compounds using crystallographic structure of the human cyclooxygenase-2 (hCOX-2) enzyme. The docking scores were compared with rofecoxib, a well-known selective COX-2 inhibitor, serving as the reference standard. The study aimed to identify novel compounds with potent therapeutic efficacy and reduced gastrointestinal side effects.

Results

Compounds 5a–5j and 9a–9j were evaluated for anti-inflammatory activity using the carrageenan-induced paw edema model. Compounds showing significant anti-inflammatory effects were further assessed for analgesic and anti-ulcer activities. Among them, compounds 5f, 5j, 9e, and 9j exhibited notable binding affinities in molecular docking studies against hCOX-2, correlating well with their observed in vivo pharmacological activities. Compounds 5f and 5j emerged as the most potent candidates, demonstrating strong anti-inflammatory activity, significant analgesic effects, and excellent ulcer-protective properties. In contrast, compounds 9e and 9j showed moderate anti-inflammatory and analgesic activity. Remarkably, compounds 5f and 5j provided maximum protection against aspirin-induced gastric mucosal damage, with ulcer inhibition rates of 91.85 and 91.39%, respectively, compared to the standard anti-ulcer agent, ranitidine.

Conclusions

In the present study, the synthesized compounds were evaluated for their pharmacological effects using the carrageenan-induced paw edema method for anti-inflammatory activity, the hot plate method for analgesic activity, and the aspirin-induced ulcer model for anti-ulcer activity. Complementary molecular docking studies were performed to assess the binding affinities of the compounds to the hCOX-2 enzyme, and those with favorable docking scores were selected for in vivo evaluation. The results demonstrated that several synthesized compounds exhibited significant anti-inflammatory, analgesic, and anti-ulcer activities, highlighting their potential as therapeutic agents.

Graphical abstract

Background

Polycystic ovary syndrome (PCOS) is a prevalent endocrinopathy characterized by excess androgen production and associated metabolic disturbances. Although several synthetic drugs, such as hypoglycemic and ovulation-inducing agents, are used in PCOS management, their clinical outcomes remain limited due to adverse side effects. Therefore, natural compounds offer promising alternatives or adjunct drugs with improved safety and efficacy.

Objective and methods

This study evaluated phytochemicals from Anethum graveolens (dill) for potential therapeutic activity against PCOS using an integrative computational strategy. PCOS-related targets were identified through DiseaseNet and GeneCards, followed by protein–protein interaction (PPI) analysis via STRING and hub gene selection with CytoHubba. Lead compounds were assessed through molecular docking, density functional theory (DFT) calculations, and to confirm the stability of the compound–target interactions, we performed molecular dynamics (MD) simulations (100 ns).

Results

The selected phytochemicals demonstrated favorable drug-likeness properties. DFT analysis revealed strong reactivity of carvacrol, eugenol, geraniol, and thymol, indicated by low energy gaps. Docking studies showed that these compounds exhibited stronger binding affinities with key PCOS targets compared to the control drug metformin. MD simulations further confirmed the stable interaction of these compounds with PCOS-associated proteins, including MMP9, AR, ALB, and PPAR-α.

Conclusion

Carvacrol, eugenol, geraniol, and thymol exhibited strong binding affinities, favorable drug-likeness profiles, and stable interactions with PCOS-associated receptors, highlighting their potential as multi-target therapeutic candidates for PCOS management.

Background

Chalcone derivatives, which are known for their non-steroidal anticancer properties, have been extensively studied. One potential application of chalcone is as aromatase inhibitors, a crucial strategy for treating estrogen receptor-positive (ER +) breast cancer. Thirteen chalcone derivatives were synthesized via the aldol condensation method, and their structural properties were characterized using FTIR, MS, and NMR. Molecular docking was performed using the Schrodinger Suite, and the QikProp program was used for in silico ADME analysis.

Results

The cytotoxicity of all 13 synthesized compounds was evaluated using the MCF-7 human cancer cell line. Additionally, specific chalcone derivatives were subjected to further aromatase inhibition testing. Four compounds, namely 3a, 3c, 3g, and 3h demonstrated significant potency, with IC₅₀ values of 20.66 ± 1.79 µM, 14.66 ± 1.09 µM, 17.96 ± 1.57 µM, and 15.52 ± 1.25 µM, respectively. Further analysis using a fluorogenic assay revealed that compounds 3a, 3c, 3g, and 3h exhibited in vitro aromatase inhibitory activities with IC₅₀ values of 4.684 ± 3.33 µM, 1.368 ± 0.90 µM, 2.124 ± 0.83 µM, and 3.314 ± 0.6123 µM, respectively. The ADME parameters of the synthesized compounds were also computed using QikProp 5.1 software.

Conclusions

Compound 3c emerged as the most potent aromatase inhibitor, with an IC₅₀ value of 1.368 ± 0.90 µM, surpassing that of letrozole. Compounds 3g and 3h also exhibited strong aromatase inhibitory activities. These findings suggest that 3c, 3g, and 3h are promising lead compounds for further research as potential anticancer agents, particularly in the context of aromatase inhibition.

Chronic kidney disease (CKD) often leads to renal fibrosis driven by CXCR4-mediated inflammation and tissue remodeling. This study aims to identify potential inhibitors of membrane-embedded CXCR4 isoform I through molecular docking and dynamics simulations. The AlphaFold-predicted human CXCR4 structure (AF-P61073-F1) was used for molecular dynamics simulations in GROMACS. Molecules with optimal ADME profiles and the top three lowest Glide scores were evaluated. Membrane simulations using RMSD, RMSF, SASA, Gyration, PCA, FEL, and per-residue decomposition analysis showed that compound 4993 interacted most stably with CXCR4. Additional simulations further confirmed 4993’s strong potential as a CXCR4 inhibitor. Furthermore, the membrane thickness, area per lipid, and Interdigitation analyses indicated that compound 4993 maintained favorable interactions contributing to membrane stability. These findings suggest that 4993 could play a significant role in modulating membrane properties, potentially contributing to its predicted effects, without implying confirmed therapeutic efficacy. Future studies should investigate the molecular mechanisms of CXCR4 interaction and their implications for drug development. The computational study concluded that membrane-embedded CXCR4 small-molecule inhibitor, such as compound 4993, has the potential to target CXCR4 and reduce kidney damage.

Background

Lagunaria patersonii, a valuable member of the Malvaceae family, holds growing economic and therapeutic interest. This study aimed to optimize the ethanolic extraction of its leaves to maximize both extract yield and concentration of tiliroside, a bioactive compound with known antioxidant and anti-inflammatory properties. Optimization was performed using Box–Behnken Design (BBD) evaluating three variables: plant material/solvent ratio, ethanol/water ratio, and extraction time. Tiliroside concentration was optimized using a dual-wavelength absorbance method which validated by UPLC-ESI–MS.

Results

Increasing the plant material/solvent ratio (Factor A) significantly increased the yield by 26-fold compared to extraction time (Factor C), while a higher ethanol/water ratio (Factor B) significantly reduced the yield. Biologically, the optimized extract demonstrated strong antioxidant activity estimated by reactive oxygen species inhibition. Importantly, the isolated tiliroside significantly inhibited nitric oxide, tumor necrosis factor-α and interleukin-6 more than the optimized extract. The BBD approach provided key insights, enabling the optimization of the extract.

Conclusion

The study effectively optimized the extraction of L. patersonii leaves and highlighted the valuable antioxidant and anti-inflammatory properties of both the optimized extract and its major compound, tiliroside. The integrated use of BBD and dual-wavelength tracking demonstrated significant value in enhancing both yield and bioactivity, offering a promising platform for developing plant-based anti-inflammatory agents. The approach applied was proved to be cost-effective.