Journal of Pharmacy and Pharmaceutical Sciences最新文献

Eco-friendly silver nanoparticles (eco-AgNPs) represent a promising convergence of green nanotechnology and precision medicine for cancer treatment. This minireview examines the therapeutic potential of silver nanoparticles (AgNPs) synthesized through eco-friendly methods using plant extracts and microorganisms. These eco-friendly AgNPs demonstrate enhanced biocompatibility and selective cytotoxicity against malignant cells. These nanoparticles target cancer through multiple mechanisms including reactive oxygen species generation, apoptosis induction, and cell cycle disruption. Selectivity is achieved through surface functionalization with targeting moieties such as antibodies and aptamers that recognize overexpressed tumor receptors. The integration of biomarker-guided design enables tumor-specific delivery by exploiting unique metabolic signatures and cellular markers characteristic of different cancer types. Furthermore, AgNP-based theranostic platforms offer simultaneous diagnostic imaging and therapeutic intervention, providing real-time assessment of treatment response and enabling personalized dosing strategies. However, clinical translation faces significant challenges including potential long-term toxicity, standardization of synthesis protocols, and regulatory approval pathways. Successful clinical implementation will require interdisciplinary collaboration to optimize nanoparticle design, establish safety profiles, and develop combination therapies that maximize therapeutic benefits while minimizing side effects. Eco-AgNPs thus offer a transformative approach to cancer treatment that combines environmental sustainability with precision targeting capabilities.

Background: Roflumilast, a highly selective phosphodiesterase 4 inhibitor, is used to treat with chronic obstructive pulmonary disease and psoriasis. We aim to determine potential roflumilast-associated adverse events (AEs) and the differences in AE signals among diverse populations.

Methods: Roflumilast's AE reports between the first quarter of 2011 and the fourth quarter of 2024 were obtained from the FDA Adverse Event Reporting System (FAERS) and Canada Vigilance Adverse Reaction Database (CVARD). The signal strength was measured by four disproportionality analysis methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

Results: In FAERS, population aged ≥65 years and oral medication users accounted for a predominant proportion in the reported cases. FDA-unlabeled respiratory, thoracic and mediastinal disorders was the only one signal categorized by system organ class met all four algorithms. Newly identified AEs such as dyspnea, condition aggravated, cough, and tachycardia could contribute valuable safety considerations for clinical practice. The analysis of the available time-to-onset data suggested that cases often occurred within the first 30 days post-treatment. These results were externally validated in CVARD, suggesting consistent findings. Notably, headache was more frequently reported among users of topical formulations and female patients, while suicidal ideation and weight loss were more commonly reported in male patients and oral medications, respectively.

Conclusion: This study confirmed established adverse reactions and identified novel AEs in real-world clinical practice by dual-database pharmacovigilance analysis. Clinicians should remain vigilant for AEs that differ by gender and route to enable early intervention and improve prognosis. The findings highlight personalized safety management, while underscoring the necessity of prospective studies to validate results and further characterize roflumilast's safety profile.

Bisphosphonates irritate the stomach and oesophagus and have a very limited absorption. The purpose of this study was to increase risedronate (RDN) oral bioavailability by causing a raft to form in the stomach. The creation of a raft prevents the irritation of the stomach and oesophagus caused by bisphosphonates. FTIR, TGA, and DSC were used to characterise the RDN, XLG, and the created formulation. In addition to a cell viability analysis utilising Caco-2 cells, the release of RDN was investigated in 0.1 N HCl, 0.5 N HCl, 1 N HCl, and simulated gastric fluid (SGF). For the pharmacokinetic investigation, the XR5 formulation and the Actonel® tablet were chosen as the test and reference formulations, respectively. Using a parallel design, twelve healthy albino rats were split into two groups, and blood samples were gathered for a whole day. RDN was distributed uniformly throughout the raft and demonstrated chemical stability by the FTIR. The formulation's thermal stability was demonstrated by the TGA and DSC. At 20 min, the SGF showed a 99.97% RDN release. When compared to the RDN suspension, the pharmacokinetics revealed better RDN values from the XLG raft. The RDN from the recently developed XR5 has a better bioavailability than the Actonel® tablet.

Objectives: To evaluate the potential risk of bullous pemphigoid (BP) in patients treated with immune checkpoint inhibitors (ICIs) and to characterize ICI-related BP (irBP) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: The present study conducted a disproportionality analysis leveraging FAERS database, spanning the first quarter (Q1) of 2004-2025 Q1. To ensure robust signal detection, we employed a quadruple analytical approach incorporating: (1) reporting odds ratio (ROR), (2) proportional reporting ratio, (3) Bayesian confidence propagation neural network, and (4) multi-item gamma Poisson shrinker algorithms. These methodologies were systematically applied to assess the potential risk of BP in patients treated with ICIs. Furthermore, temporal characteristics of adverse event emergence were quantitatively assessed to delineate the time-to-onset patterns.

Results: There are 850 irBP cases identified, comprising reports associated with the following agents: nivolumab (n = 530), pembrolizumab (n = 180), ipilimumab (n = 44), atezolizumab (n = 40), cemiplimab (n = 24), durvalumab (n = 19), tislelizumab (n = 10), and avelumab (n = 3). Affected patients were predominantly males (67.8%) and over 60 years of age (70.1%). All eight ICIs showed positive disproportionality signals, with ROR values ranked descendingly as: cemiplimab > nivolumab > tislelizumab > pembrolizumab > ipilimumab > durvalumab > atezolizumab > avelumab. The median time of irBP onset was 165.2 (IQR: 56-410) days.

Conclusion: The study establishes a significant link between ICIs and BP. All ICIs increase BP risk. CTLA-4 inhibitors exhibited the most marked early risk concentration, highlighting the importance of early dermatologic evaluation after initiating CTLA-4 blockade.

Gastric cancer remains a highly prevalent and accounts for a notable proportion of global cancer mortality. Both Intrinsic and exogenous agents can exacerbate reactive oxygen species (ROS) related oxidized DNA base lesions and single stranded DNA breaks (SSBs). Base excision repair (BER) serves as the primary defense mechanism for repairing DNA damage induced by oxidative stress. DNA polymerase beta (Pol β) plays a critical role in BER and non-homologous end joining repair pathways. The Pol β is the first perform gap-filling DNA synthesis by its polymerase activity and then cleave a 5'-deoxyribose-5-phosphate (dRP) moiety via its dRP lyase activity. Furthermore, defect in POLB promotes genetic liability of the cancer cells for different targeted and synthetic lethality-based treatment strategies. In this review, we have provided a potential example to illustrate the mechanistic insight how PARP1 inhibitor (Olaparib) induces replication associated double strand breaks in POLB deficient cells and DNA mediated innate immune signal activation that likely enhances immune based therapy. Based on our previously published data and the current recent findings, POLB status of the patient likely provide genetic indicators to stratify gastric cancer patient. Overall, in this review article, we presented a new direction to highlight the opportunity to exploit POLB genetic defect in cancer cells to enhance treatment response and to explore synergistic effect to target gastric cancer cells that harbor aberrant DNA polymerase beta function with immune based therapeutic strategy.

Introduction: Azathioprine (AZA) is an immunosuppressant approved for renal transplant rejection and rheumatoid arthritis. Recent FDA alerts have raised concerns about its link to intrahepatic cholestasis of pregnancy (ICP), a condition with serious maternal and fetal risks. This study used disproportionality analysis as a hypothesis-generating approach to evaluate the reporting association between AZA and ICP during pregnancy and to compare AZA with other drugs previously implicated in ICP.

Methods: A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) reports from 1968 to Q2 2024. Disproportionality analysis was performed using reporting odds ratios (RORs), with statistical significance defined as a lower limit of the 95% confidence interval (CI) >1 and at least three unique cases. Subgroup analyses were conducted by pregnancy status and underlying autoimmune indications, and comparative analyses were performed against drugs previously reported to induce ICP.

Results: Among 35,576 AZA-related reports, 67 specifically documented ICP. A strong signal was detected for ICP ROR025 = 153.0; IC025 = 5.8; EBGM05 = 144.37), ranking among the highest AZA-associated adverse events. In pregnant women, ICP also showed a significant signal (ROR025 = 5.46; IC025 = 1.93; EBGM05 = 5.31). Subgroup analyses by indication revealed elevated risks in Crohn's disease (ROR025 = 66.99; IC025 = 4.8; EBGM05 = 64.73), and Colitis ulcerative (ROR025 = 9.01; IC025 = 1.95; EBGM05 = 9.95). Comparative analyses demonstrated that AZA had a higher proportion of ICP cases than other drugs reported to induce ICP.

Conclusion: This pharmacovigilance analysis identifies a disproportionality signal suggesting a possible association between AZA and intrahepatic cholestasis of pregnancy. These hypothesis-generating findings underscore the importance of cautious use and clinical vigilance when prescribing AZA to women of reproductive age.

Objective: Mutations in the tafazzin gene lead to impaired remodeling of cardiolipin, thereby impairing mitochondrial function and causing Barth syndrome (BTHS), a rare X-linked genetic disorder characterized by cardiomyopathy. Previous studies in a mouse model of BTHS, secondary to knockdown of Tafazzin (TazKD mice), also observed perturbations in mitochondrial substrate metabolism and a hypertrophic cardiomyopathy. BTHS may be characterized by increased cardiac ketone metabolism, as myocardial protein expression of the ketolytic enzyme, β-hydroxybutyrate dehydrogenase 1 (BDH1), was markedly increased in TazKD mice. We therefore determined whether increasing ketone supply in TazKD mice may have therapeutic utility against their cardiac abnormalities.

Methods: We treated TazKD mice and their wild-type littermates with either the sodium-glucose cotransporter-2 inhibitor, empagliflozin (10 mg/kg), or a ketone ester (KE; 1719 mg/kg) once daily for 7-week, and performed ultrasound echocardiography to assess cardiac structure and function.

Results: Treatment of TazKD mice with either empagliflozin or a KE increased circulating ketone levels. However, neither approach proved capable of alleviating the cardiac hypertrophy present in TazKD mice, as their increased left ventricular wall thickness and decreased left ventricular diameter remained comparable to that observed in vehicle control treated animals. We also observed that empagliflozin and KE treatment did not impact key markers of cardiac hypertrophy in TazKD mice.

Conclusion: Increasing circulating ketone levels did not alleviate the cardiac hypertrophy in TazKD mice, suggesting that such an approach would not improve outcomes in BTHS.

In paediatric wards, bisoprolol, betaxolol, or nadolol can be administered orally at non-licensed dosages. To provide paediatric patients with appropriate treatment, batches of beta-blocker oral suspensions must be compounded, which involves subsequent stability studies. A stability-indicating HPLC-UV method and microbiological analyses were validated. Experimental batches were compounded (betaxolol hydrochloride 1 mg.mL^-1, bisoprolol hemifumarate 0.5 mg.mL^-1 and nadolol 10 mg.mL^-1). Bisoprolol hemifumarate 0.5 mg.mL^-1 and nadolol 10 mg.mL^-1 needed the addition of citric acid (3 mg.mL^-1) and potassium sorbate (3 mg.mL^-1) to ensure preservative efficacy. Betaxolol hydrochloride 1 mg.mL^-1 was stable for 2 months when stored at 2-8  °C, for 1 month after opening at 2-8 °C, and for 15 days when stored at 25 °C/60% RH. Bisoprolol hemifumarate 0.5 mg.mL^-1 was stable for 2 months when stored at 2-8 °C, for 1 month after opening at 2-8 °C, and for 15 days when stored at 25 °C/60% RH. Nadolol 10 mg.mL^-1 was stable for 3 months when stored at 2-8 °C, for 1 month after opening at 2-8 °C, and for 15 days when stored at 25 °C/60% RH. Hospital pharmacies can compound batches of beta-blocker liquid oral suspensions and store them for secure dispensing and administration.

Medication waste is a significant global concern with environmental, economic, and healthcare implications. In Saudi Arabia, approximately 25.8% of dispensed medications are wasted, resulting in an annual cost of $150 million. Re-dispensing unused medications has been proposed to reduce this waste; however, its feasibility depends on public acceptance, regulatory frameworks, and assurances of safety. This study aimed to assess the Saudi public's willingness to accept re-dispensed medications returned unused to pharmacies and to identify factors influencing this willingness. A descriptive cross-sectional survey was conducted online across Saudi Arabia. The questionnaire, adapted from a validated tool by McRae et al. McRae et al. (Pharmacy (Basel), 2021, 9(2): 77) and translated into Arabic, explored demographics, medication practices, storage and disposal, and attitudes towards medication waste and re-dispensing. The survey was distributed via social media. Data were analyzed using SPSS version 29, including chi-squared tests and binary logistic regression. A total of 405 participants completed the survey, primarily female (64%) and aged 25-44 years (43%). About 64% reported having unused medications at home, most commonly stored in bedrooms (55.1%) and kitchens (53.6%). Disposal practices included keeping medicines for future use (62.5%), discarding them with household waste (45.7%), sharing them with others (21.5%), and returning unused medications to a pharmacy (8.4%). Approximately 60% were willing to accept re-dispensed tablets and 55% capsules, whereas fewer accepted other dosage forms. Key factors influencing acceptance included pharmacist verification of quality and integrity (79.3%), informed consent (77.3%), expiry dates (77%), and intact packaging (74.8%). Most participants (68.1%) indicated they would return unused medicines if a re-dispensing program were implemented, and half (50.6%) believed all medications, not only expensive ones, should be considered. Significant predictors of willingness included age (P < 0.001), employment status (P = 0.004), regular prescription use (P = 0.046), and concern about waste (P < 0.001). Younger participants showed higher acceptance, while employed individuals, retirees, and regular medication users were more hesitant. The findings indicate cautious yet notable public support for medication re-dispensing in Saudi Arabia, particularly for oral solid dosage forms, provided rigorous safety measures are assured. Policymakers should consider these insights to guide initiatives aimed at reducing medication waste.

Background: Hypoglycemia is a common yet underrecognized complication in patients with type 2 diabetes mellitus (T2DM), often linked with increased cardiovascular (CV) morbidity and mortality. Despite its clinical importance, there is a limited data on the association between hypoglycemia, CV events, and mortality among T2DM patients in Rwanda. This study investigated the occurrence of hypoglycemia and its association with CV diseases, morbidity, and mortality in T2DM patients attending two university teaching hospitals in Rwanda.

Methods: A retrospective study was conducted using secondary data from 267 T2DM patients attending Kigali University Teaching Hospital (CHUK) and Butare University Teaching Hospital between 2015 and 2020. Socio-demographic and clinical data, including anti-diabetic medications, hypoglycemia episodes, CV events, and comorbidities, were extracted from medical records and analyzed using Python. Binary regression was used to determine significant predictors of hypoglycemia.

Results: Hypoglycemia occurred in 112 (41.9%) patients during their hospitalization or hospital admissions. The use of insulin was significantly associated with hypoglycemia (OR = 1.590, CI: 1.100-2.290, p = 0.010). The mean age of patients who experienced hypoglycemia is 54.2 (±12.1) years. Hypoglycemia occurrence was higher in males (59.8%) group compared to females (40.2%) (p = 0.007). Cardiovascular conditions were common (73.8%), with hypertension being the most prevalent (85.4%). Insulin was the most frequently used anti-diabetic therapy (42.3%). A significant association was found between hypoglycemia and subsequent CV complications. Management of hypoglycemia predominantly involved the use of 50% dextrose solution.

Conclusion: Hypoglycemia is a frequent and clinically significant occurrence among T2DM patients in Rwanda, particularly associated with insulin therapy and CV comorbidities. Enhanced clinical monitoring and individualized treatment regimens are essential to mitigate hypoglycemia-related complications and reduce mortality. It is important to conduct a larger studies to support the evidence based findings and address the current methodological constraints.