Future Journal of Pharmaceutical Sciences最新文献

Background

Preventable drug-related incidents (PDRIs) remain a major challenge to patient safety, particularly in hospitals that manage complex infectious diseases. However, data on their frequency and characteristics in such settings are scarce. This study estimated the incidence of PDRIs in a specialized infectious diseases hospital and identified the most frequent incident types.

Methods

This prospective study consecutively included adults (≥ 18 years) admitted to the clinical ward of a tertiary infectious diseases hospital from June 13, 2019, to March 6, 2020, and followed them until discharge. Recruitment was originally planned for 12 months but was interrupted after nine months due to COVID-19-related operational restrictions. PDRIs were assessed every seven days through systematic prescription review and classified using the Severity Assessment Code (SAC).

Results

A total of 212 hospitalized patients were analyzed, of whom 78.8% experienced at least one PDRI. Drug interactions, scheduling errors, dosage mistakes, and adverse drug reactions were the most frequent incidents. The incidence rate was highest during the first week of hospitalization and decreased thereafter. Higher PDRI rates were observed among adults aged 39–60 years, females, patients with comorbidities, and those with infectious diagnoses such as Chagas disease, sporotrichosis, tuberculosis, and HIV/AIDS.

Conclusions

PDRIs were frequent and strongly associated with clinical complexity and early hospitalization. These findings underscore the critical role of clinical pharmacists in early intervention, systematic prescription monitoring, and implementation of preventive strategies to reduce medication-related harm in infectious disease settings.

Background

Ulcerative colitis (UC) is the most common type of inflammatory bowel disease (IBD) whose pathogenesis may involve inflammation, oxidative stress, apoptosis and fibrosis. The aim of this study is to ameliorate UC pathogenic mechanisms by using perindopril (PER; 2 mg/kg/day), an antihypertensive drug acting by inhibition of angiotensin-converting enzyme, and/or α-pinene (APN; 50 mg/kg/day), a naturally occurring volatile organic compound known for its anti-inflammatory and antioxidant effects, in comparison with the traditional treatment sulfasalazine (SSZ; 100 mg/kg/day) in acetic acid-induced UC in rats.

Results

The results showed that PER and/or APN improved UC macroscopic and microscopic lesions, while functionally decreasing the disease activity index. PER and/or APN also improved the oxidative status by decreasing malondialdehyde and nitric oxide while increasing reduced glutathione in UC-induced colons. Compared to UC group, animals treated with SSZ, PER, APN and PER + APN had increased levels of the anti-inflammatory cytokine IL-10 by 3.0, 1.9, 2.3 and 3.8 folds, respectively. Furthermore, compared to UC group, JAK-2 was declined by 51%, 39.2%, 42.8% and 60.7% and p-STAT3/STAT3 ratio was decreased by 41.4%, 46.5%, 50.9% and 58.6%, while SOCS3 levels were increased by 2.8, 2.0, 2.2 and 3.4 folds in SSZ, PER, APN and PER + APN groups, respectively. In addition, the pro-fibrotic marker MMP-9 was decreased by 51.7%, 58.2%, 55.1% and 66.13% and the pro-apoptotic markers also were decreased by 51.9%, 51.6%, 55.8% and 68.8% for c-caspase 3 and 47.7%, 53.8%, 54% and 67.6% for cytochrome C in SSZ, PER, APN and PER + APN groups, respectively. For MIR-98-5p, a microRNA known to have a role in IBD, it was decreased compared to UC group by 61.6%, 47.2%, 52.1% and 74% in SSZ, PER, APN and PER + APN groups, respectively.

Conclusion

In conclusion, to the best of our knowledge, this is the first study to demonstrate that PER and APN can modulate the JAK-STAT3-SOCS3 signaling axis and MIR-98-5p in UC model, to levels comparable to the traditional therapy with SSZ, and can be considered novel modulators of JAK-2/STAT3/SOCS3 and miR-98-5p in colon.

Graphical abstract

Background

Inadequate selectivity, toxicity, high costs, low bioavailability, and susceptibility to drug resistance are all therapeutic limitations associated with resistant breast cancer treatments. Therefore, the present challenge is to develop highly effective anti-breast cancer targets. Within this context, the current study aims to develop amino acid-based cholesteryl ester complexes (AACE) for targeting triple-negative breast cancer cells (MDA-MB-231).

Results

The results of in vitro cytotoxicity for AACE (PHC, PRC, VAC) complexes on triple-negative breast carcinoma (MDA-MB-231), lung cancer (A549), and normal breast cells (MCF-10A) revealed significant potency and selectivity against MDA-MB-231 cells (IC₅₀ PHC = 32.58 μM, PRC = 42.76 μM, VAC = 59.23 μM) and good cytocompatibility over normal breast cells (MCF-10A) compared to erlotinib. All of the complexes demonstrated a lower cytotoxic impact on A549 cells (lung cancer) compared to erlotinib. The most cytotoxic complex, PHC, showed good DNA cleavage ability. Moreover, PHC and PRC complexes, along with erlotinib, showed hemocompatibility in the concentration range of 3.125-50 μM but revealed mild hemolytic toxicity at high concentrations (100 μM). Molecular docking analysis (3EQM-PHC = -9.16, 3EQM-PRC = − 9.55 kcal/mol; 1M17-PHC = − 8.39, 1M17-PRC = − 8.84 kcal/mol) revealed strong binding interactions of aromatase and EGFR proteins with all the complexes. Additionally, DFT studies showed a good correlation between ∆E values (PHC = 5.811 eV, PRC = 6.2563 eV), suggesting the good bioactivity of PHC. All complexes showed compliance with drug-likeness and ADMET requirements.

Conclusions

The results of cytotoxicity (MDA-MB-231), biocompatibility (MCF-10A), DNA cleavage, in vitro hemolysis, DFT, molecular docking, and ADMET evaluations indicate the significant potential of PHC as a possible target for resistant breast cancer cells (MDA-MB-231).

Graphical Abstract

Background

Formononetin (FNT), a phytoestrogen, has shown osteogenic effects in ovariectomy-induced osteoporosis, but its therapeutic use is limited by poor bioavailability. This study aimed to compare the osteogenic potential of pure FNT and formononetin–piperine–phospholipid complex (FNT-PIP-PC) in OVX-induced osteoporosis and to quantify free FNT concentration in rat bone marrow. An in vivo study was conducted using an OVX-induced osteoporosis rat model. Adult female Sprague–Dawley (SD) rats were ovariectomized and treated orally with FNT or FNT-PIP-PC at 5mg/kg for 12 weeks. Therapeutic efficacy was evaluated using body composition analysis, µCT, L5 compression, bone markers, and pharmacokinetics parameters in the bone marrow via LC–ESI–MS/MS.

Results

FNT-PIP-PC treatment significantly restored trabecular bone volume and microarchitecture in the femur and tibia, improved uterine mass, increased osteocalcin (OCN), and reduced C-terminal telopeptide of type 1 collagen (CTX) levels. These findings aligned with enhanced mRNA expression of RUNX, RANKL, BMP2, and OPG. Additionally, FNT-PIP-PC improved pharmacokinetic parameters like C_max, AUC_0-t, and AUC_0-∞ of free FNT from FNT-PIP-PC compared to pure FNT.

Conclusion

Oral administration of FNT through complexation with PIP reduced phase II metabolism and enhanced free FNT concentrations, leading to a significant increase in its bioavailability in bone marrow, supporting the targeted delivery. Furthermore, the FNT-PIP-PC complex demonstrated a marked improvement in the osteogenic potential of FNT on OVX-induced osteoporosis rats with no significant adverse effects. Collectively, these findings support the FNT-PIP-PC potential as a safe and effective therapeutic option for postmenopausal osteoporosis.

Graphic abstract

Background

Dyslipidemia constitutes one of the foremost metabolic abnormalities contributing to cardiovascular morbidity and mortality. Washed microbiota transplantation (WMT), a refined form of fecal microbiota transplantation, has emerged as a novel therapeutic option targeting gut-liver axis dysregulation. This systematic review and meta-analysis, registered on PROSPERO (CRD42025645142), evaluated the efficacy of WMT in modulating lipid profile parameters. A comprehensive search was conducted across PubMed, Scopus, EMBASE, CENTRAL, Google Scholar, and ClinicalTrials.gov for studies assessing WMT effects on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Eligible studies included adults receiving WMT without concurrent lipid-lowering or microbiota-modifying therapies. Data were pooled using random-effects meta-analysis. MINORS tool was used to assess methodological quality.

Results

Seven studies encompassing 1,163 participants were included. Across all study groups, WMT significantly reduced short-term TC (MD = –0.18; 95% CI –0.32 to –0.03) and long-term TG (MD = –0.08; 95% CI –0.11 to –0.05). LDL-C showed a significant long-term decrease (MD = –0.24; 95% CI –0.46 to –0.02), whereas HDL-C changes were non-significant overall. In participants with baseline hyperlipidemia, WMT consistently improved TC (short- and medium-term) and HDL-C (short-term), while effects on LDL and TG remained non-significant. Meta-regression demonstrated that higher baseline TC, HDL-C, and TG levels predicted greater post-WMT improvements (all p < 0.01). The overall certainty of evidence was low for most outcomes due to heterogeneity and observational study design.

Conclusion

WMT may improve lipid profiles, especially in patients with elevated baseline lipids, offering a microbiota-based adjunct for dyslipidemia management. High-quality RCTs and optimized protocols are needed to confirm long-term efficacy.

Background

Eczema remains a challenging dermatological condition affecting millions worldwide and current treatments often present limitations and side effects. Dodder or Cuscuta reflexa has documented anti-inflammatory, antioxidant, and antimicrobial properties that may benefit skin conditions. The goal for this study was to develop and optimize a novel topical hydrogel with anti-eczema activity using C. reflexa extract for eczema management. Evaluation parameters included physicochemical characterization like viscosity, pH, spreadability, in vitro drug release, ex vivo permeation, skin irritation, and in vivo efficacy using DNCB-induced eczema model.

Results

The hydrogel was formulated using varying concentrations of Carbopol 934 as the gelling agent. Response surface methodology optimized the formulation, yielding ideal physicochemical properties: viscosity (14,872 cP), pH (6.32), and spreadability 76%. In vitro studies demonstrated sustained release with 64.00% cumulative release over 14 h. Ex vivo permeation study optimized formulation showed 9% permeation and 48% retention in 4 h. Skin irritation study indicated that the optimized hydrogel formulation is safe for topical application without causing skin irritation. In vivo evaluation in an eczema model induced by 2,4-dinitrochlorobenzene (DNCB) in ICR mice showed significant improvement in clinical symptoms and histopathological parameters.

Conclusion

The developed C. reflexa hydrogel formulation represents a promising natural alternative for eczema management, demonstrating optimized formulation, exhibits favorable physicochemical properties, sustained release characteristics, and therapeutic efficacy in eczema models.

Graphical Abstract

Background

Migraine is a neurological disorder and major cause of disability globally, especially in women and young adults. This study aimed to investigate the beneficial effects of polydatin (PD), a natural compound, against nitroglycerin (NTG) induced migraine like headache in mice.

Materials and methods

Behavioural paradigms included Von Frey filament test, tail flick test, light aversion test and assessment of migraine-associated pain like behaviour. In addition, biochemical investigations were undertaken to determine the effect of PD on migraine associated markers including oxidative stress, nitric oxide (NO) and calcitonin gene related peptide (CGRP). Integrated in vivo, in silico, and network pharmacology approaches were employed to evaluate PD’s antimigraine effects. Statistical significance was set at p < 0.05.

Results

Treatment with PD attenuated NTG-induced migraine like headache and related behavioural changes. PD-subjected animals exhibited enhanced levels of catalase, glutathione-S-transferase, and glutathione, as well as reduced lipid peroxidation, compared to NTG-only treated animals. Reduction in CGRP and nitrite levels along with reduced expression of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was also observed in mouse cortex and trigeminal nucleus caudalis (TNc) after treatment with PD compared with disease controls. Histological sections from PD treated animals from these regions resembled closely with those of controls with improved cell viability. Molecular docking studies suggested that PD docked in the similar binding pocket as that of CGRP, Rimegepant (a CGRP receptor blocker) and Sumatriptan. Network pharmacology revealed potential interaction of hub genes with PD, with proteins like NOS1 (nNOS), NOS2 (iNOS), NOS3, PDE5A, GATM, ARG1 and ARG2 having significant role in network functionality and the potential mediation of PD therapeutic effect.

Conclusion

PD ameliorated NTG-induced migraine like headache through modulation of NO, CGRP and oxidative stress dependant mechanisms.

Background

The genus Cynanchum, family Apocynaceae is a group of climbing vines that have long been in folk medicine used as antitussives, analgesics, anticonvulsants, expectorants, diuretics, antifebriles, and tonics.

Results

Cynanchum acutum crude extract was investigated to determine its chemical composition through LC-ESI-TOF-MS/MS technique, where 46 hits were observed. Among these compounds, quercetin-3-O-β-galactoside was previously reported within the plant as a major component. This compound was isolated and purified using different chromatographic techniques, and its concentration was estimated using high-performance thin-layer chromatography (HPTLC). Two semi-synthetic derivatives were synthesized from this compound, namely 7-benzyl- and 7-bromoethyl quercetin-3-O-β-galactosides. Both analogs, which are more hydrophobic, were developed as an attempt to improve the physiochemical properties and, in turn, the pharmacokinetics of the parent compound. Our study also includes the determination of antiviral activity against COVID-19 of Cynanchum acutum crude extract along with quercetin-3-O-β-galactoside in addition to the two semi-synthesized derivatives. The antiviral assay revealed that the synthetic benzyl derivative of quercetin-3-O-β-galactoside demonstrated promising activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The potential molecular aspects of the parent and semi-synthetic analogs were highlighted through molecular modeling simulation of docking the compounds at the viral main protease (Mpro) binding pocket. In silico findings demonstrated significant affinity and residue-wise binding interactions in relation to the co-crystallized small molecule Mpro inhibitor.

Conclusion

Collectively, our study adds to the current knowledge of SARS-CoV-2 pharmacotherapy by introducing drug-like small molecules with potential activity profiles.

Graphical abstract