Saudi Pharmaceutical Journal最新文献

Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Conventional therapies, including surgery, chemotherapy, and targeted treatments, often show limited efficacy, especially in advanced stages. Pulmonary drug delivery systems (PDDSs) have gained attention as an innovative approach for NSCLC management by enabling direct drug administration to the lungs. This method improves therapeutic outcomes while minimizing systemic side effects. Advances in nanotechnology have further enhanced the potential of inhalable chemotherapy, with nanoparticles offering notable benefits such as improved drug solubility, stability, and protection from premature degradation. Additionally, their small size and modifiable surfaces allow for targeted delivery to tumor cells, increasing treatment efficacy and reducing harm to healthy tissues. This review outlines the formulations used in PDDSs for NSCLC, evaluates suitable inhalation devices, and examines the physicochemical characteristics of nanoparticles critical for pulmonary delivery. It also discusses both passive and active targeting mechanisms and explores current challenges in inhalable nanomedicine. Emphasis is placed on recent innovations in inhalable nanomaterials, providing a comprehensive and current perspective on their application in NSCLC therapy.

Osteomyelitis (OM) is a serious bacterial bone infection and can be life-threatening if not treated promptly. A promising approach to manage OM involves using drug-loaded fibrous implants or scaffolds containing antibiotics, analgesics, or anti-osteoporosis medications to combat infection, reduce pain and promote bone healing, respectively. In this study, a coaxial electrospinning technology was employed to fabricate drug-loaded fibers encapsulating vancomycin hydrochloride (VAN), an antibiotic, and diclofenac sodium (DIC), an analgesic to prevent infection and alleviate post-surgical pain. The fibers were characterized using scanning electron microscopy (SEM) which indicated that the drug-loaded (DL) coaxial fibers had smooth surfaces and lacked beads and pores. The drug loading of the DL coaxial fibers was estimated by high-performance liquid chromatography (HPLC), and the results were calculated as 75 ± 4 µg/mL for VAN and 82 ± 3 µg/mL for DIC. The drug release was also measured by HPLC, which showed a rapid initial release, i.e., 59% for VAN and 75% for DIC within the first day, followed by a sustained slow release reaching approximately 92% and 79%, respectively after 264 h. The antimicrobial assay zone of inhibition confirmed the antibacterial activity of the DL fibers against Staphylococcus aureus. The cell viability assessments on the drugs alone against human dermal fibroblasts (HFF-1) demonstrated that the VAN and DIC combination is safe at concentrations up to 250 µg/mL but required careful dosing due to time-dependent cytotoxicity. Overall, the study highlights the potential use of VAN and DIC-loaded coaxial electrospun fibers as a localized drug delivery system for OM treatment, offering controlled drug release, effective antibacterial action, and biocompatibility.

Practically, all patients treated with Minoxidil (MXD) reported experiencing hypertrichosis, even though the original intended usage of the drug was the treatment of hypertension. This limitation supports the potential of repurposing MXD as a topical agent for the treatment of hair loss. Accordingly, the outset of the current study was to exploit the cutaneous influence of MXD and limit the drawbacks of conventional available dosage forms. This could be achieved via developing a nanocarrier, mainly; nanoemulsion (NE) for transdermal delivery of MXD. Therefore, several NEs were prepared containing MXD and optimized according to their particle size and in vitro release study using Response Surface Methodology. The optimized formulation was examined for its organoleptic properties, pH, viscosity, and drug content. Moreover, Morphology, kinetic study was investigated a long with the stability testing upon keeping in two distinct settings: room temperature and refrigerator for 12 months. Eventually, the in vivo hair growth rate was monitored and documented for 28 days in pretreated mice. The developed MXD-NEs were developed and optimized using Box Behnken Design software to obtain the most desired formula. The optimized MXD-NE demonstrated a nanosize (83.1 nm) and performs a successful in vitro release (75.6%) over a period of 6 h. Additionally, it showed ideal physical properties with pH (5.9), viscosity (26.7 cP), and drug content (99.4%). The droplets in the formula seemed to be spherical. The formula was stable when preserved for 12 months at both applied conditions. Finally, the formula demonstrated significant faster rate of hair growth that mostly owed to the value of nanocarrier in delivering drug into follicular hairs.

Colistin is an antibiotic that belongs to the polymyxin family. It has reemerged as a treatment of last resort against multi-drug resistant gram-negative bacterial infections. Nephrotoxicity remains the most daunting and limiting adverse effect of colistin therapy leading to treatment discontinuation and mortality in high-risk patients. Nephrotoxicity occurs secondary to the accumulation of colistin in the renal proximal tubular epithelial cells (RPTECs). Mechanistically, colistin exerts endoplasmic reticulum and ribotoxic stress, induces mitochondrial dysfunction and oxidative stress in the RPTECs leading to apoptosis and necrosis. Moreover, colistin activates the mitogen-activated protein kinases and perturbs the balance between survival-promoting and death-promoting growth factors. In this review we have presented and integrated the major in vitro and in vivo mechanistic studies undertaken to study colistin-induced nephrotoxicity. In addition, we have suggested a possible unifying mechanism for colistin renal toxicity based on the emerging concept of the cross-organelle stress response.

Artemisia sieberi Besser (A. sieberi) has shown promise as a natural source of safe cytotoxic agents for breast cancer therapy. However, its effects on triple-negative breast cancer (TNBC), a very aggressive subtype lacking targeted treatments, remain poorly studied. This study evaluates the anticancer activity of A. sieberi extracts against the MDA-MB-231 TNBC cell line, comparing results with hormone receptor-positive MCF-7 cells. Aerial parts of A. sieberi were extracted using ethanol and methanol and then chemically characterized via gas chromatography/mass spectrometry (GC/MS) to identify bioactive compounds. Cytotoxic effects were assessed using cell viability assays, while apoptosis induction was examined through flow cytometry (Annexin V/propidium iodide staining), caspase-3/-7 activation assays, and mitochondrial membrane permeabilization visualized using confocal microscopy. Western blotting analyzed the expression levels of apoptotic proteins. In silico molecular docking simulations explored the interactions between phytochemicals and apoptosis-regulating proteins. A. sieberi extracts exhibited higher cytotoxicity against MDA-MB-231 cells than against MCF-7 cells, with lower IC₅₀ values. Treatment of TNBC cells induced apoptosis, evidenced by increased caspase activity, mitochondrial membrane permeabilization, elevated Bax, and decreased Bcl-2 expression. Additionally, colony formation assays demonstrated a significant reduction in tumorigenic potential. Computational analyses indicate that β-sitosterol and stigmasterol, among the main compounds, exhibited strong interactions with apoptosis regulators by docking with Bcl-2, supporting their promising anticancer potential. A. sieberi extracts induce potent apoptosis and exert anti-tumour effects in TNBC cells, highlighting their potential as sources of novel anticancer agents. Further isolation and characterization of active constituents are warranted for therapeutic development.

There is a need for assessing the impact of current drug availability regulations across the various stages of the pharmaceutical supply chain and among different stakeholders involved. This mixed methods survey assessed the impact of pharmaceutical availability regulations across the drug supply chain in Saudi Arabia. This research utilized a cross-sectional study design involving a survey conducted at a single point in time to collect data from key stakeholders across the various stages of the pharmaceutical supply chain. Various metrics, such as availability ratings, accessibility issues, and stakeholder perspectives on regulatory effectiveness were examined. Mixed methods analysis combined survey statistics with qualitative insights. The data source for this study comprised an online survey targeting key stakeholders involved along the pharmaceutical supply chain (n = 27), including drug manufacturers (n = 10), distributors (n = 4), and healthcare settings, such as hospitals (n = 9) and pharmacies (n = 4). The data were collected in September 2023. Manufacturers (mean availability rating of 3.8) and distributors (mean availability rating of 3.5) viewed regulations to be more effective versus hospital/pharmacies (mean availability rating of 3.3) citing lack of harmonization and transparency as key efficiency deterrents. Centralized inventory monitoring and unified availability benchmarks were strongly advocated as enhancements alongside improved communication flows. Ultimately, a collaborative, yet guided approach is imperative for balancing industrial priorities and access imperatives to attain synchrony across the pharmaceutical value chain in order to augment both health and economic outcomes.

While several anti-tumor biosimilars have been approved in China, comprehensive nationwide analyses of their real-world utilization patterns remain limited, particularly regarding cross-regional adoption and indication-specific usage. We collected information on patients treated with bevacizumab, rituximab, trastuzumab and their biosimilars at 109 hospitals in nine Chinese cities from 2019 to 2023. Analysis of 264,527 prescriptions revealed rapid biosimilar adoption for bevacizumab (2023 originator share: 20.0%, -25.1%/year), moderate for rituximab (32.1%, -16.8%/year), and limited for trastuzumab (70.0%, -8.3%/year). Geographic variation was substantial (2023 city ranges: bevacizumab 2.3-43.0%; rituximab 6.7-70.3%; trastuzumab 42.4-92.4%). Tertiary hospitals showed faster biosimilar uptake than secondary hospitals (bevacizumab: + 23.7%). Free medical care patients preferred originators (bevacizumab: 64.1% vs 38-39% for other payers). Off-label use demonstrated significantly higher biosimilar adoption (bevacizumab: 69.0%; rituximab: 52.1%) versus approved indications (p < 0.00625). Cost distributions mirrored prescription trends but consistently favored originators. All trends were statistically significant (p < 0.05). The biosimilar market share showed steady annual growth, however the growth rates vary across different products. However, Patients with lower out-of-pocket costs remained more likely to choose original products. Enhanced regulatory oversight of both approved and off-label/extrapolated indications is needed to ensure appropriate biosimilar utilization.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a novel group of oral medications used to treat type 2 diabetes mellitus (T2DM). Nonalcoholic fatty liver disease (NAFLD), a complication of T2DM, is now recognized as one of the most frequent causes of chronic liver disorders. We aimed to investigate the effects of SGLT2is on hepatic function and glucose homeostasis in patients with T2DM and comorbid NAFLD. To our knowledge, this is the first study in the Arab region to compare the effects of SGLT2is and other antidiabetic medications and to evaluate the outcomes after a 6-month follow-up period in this patient cohort. This cohort study involved 100 patients with T2DM. The patients were divided equally into two groups. The exposed group comprised 50 patients receiving any of the SGLT2is (empagliflozin or dapagliflozin); the non-exposed group comprised 50 patients taking any other oral antidiabetic medication (other than glucagon-like peptide-1 receptor agonists or SGLT2is). The outcomes investigated were glycemic control, hepatic function, and liver fibrosis parameters, investigated at baseline and after 6 months. Significant improvements in glycemic control, hepatic function, and fibrosis parameters were observed in the SGLT2i group after 6 months, as evidenced by laboratory and clinical data (p < 0.001). Significant improvements were observed in hemoglobin A1c, Fibrosis-4 index, gamma-glutamyl transferase level, alanine aminotransferase level, and NAFLD fibrosis score (p < 0.05). The findings indicate that 6 months of SGLT2i therapy improved fibrosis and glucose homeostasis in patients with T2DM and NAFLD. Therefore, SGLT2is are effective therapeutic agents in this patient population.

Antimicrobial resistance (AMR) is rising alarmingly in Saudi Arabia, as evidenced by surveillance data. This retrospective cohort study evaluated the association between parenteral antimicrobial use and bacterial resistance at King Khaled Hospital, Al-Kharj, using electronic health records. Linear regression analyzed antibiotic exposure-resistance relationships over 36 months (January 2022-December 2024). Eligible participants were hospitalized ≥ 48 h and received ≥ 1 parenteral antimicrobial. The required sample size was 384 (calculated via Cochran's formula). Inclusion mandated laboratory-confirmed bacterial infections (positive cultures with susceptibility testing). Investigated pathogens included Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Among 4,007 participants, 59.02% were female, and 73.07% were Saudis. Findings revealed severe AMR, particularly in Escherichia coli and Klebsiella pneumoniae, with high resistance to multiple antibiotic classes. Acinetobacter baumannii exhibited near-pan-drug resistance (> 90% resistance to most antibiotics). Imipenem use strongly correlated with Escherichia coli resistance (R² = 1.000, p-value = 0.009), indicating significant carbapenem-driven selection pressure. Meropenem exposure also closely linked to Klebsiella pneumoniae resistance (R² = 0.994, p-value = 0.050). Widespread resistance to β-lactams, fluoroquinolones, and aminoglycosides-combined with near-pan-resistant Acinetobacter baumannii-highlights escalating treatment challenges. Crucially, carbapenem usage (imipenem/meropenem) strongly predicted resistance in Escherichia coli and Klebsiella pneumoniae, reinforcing antimicrobial pressure's role in resistance development. These results emphasize the urgent need for antimicrobial stewardship at King Khaled Hospital to curb carbapenem overuse and combat resistant infections.

A novel class of antidiabetic drugs known as sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) prevents the renal proximal tubules from reabsorbing glucose. While a recent study showed that SGLT2-Is may be able to slow the proliferation of cancer cells that express SGLT2, limited evidence exists regarding their effects on renal cell carcinoma (RCC). Here, we examine the ability of the SGLT2-I canagliflozin (Cana) to prevent experimentally induced kidney carcinogenesis in male rats. A total of twenty-four rats were divided into four groups, six in each: negative control, DEN/TAA control; rats (60-70 g) were fed a choline-deficient diet (CDD) for 4 weeks, then rats were subjected to four doses of 50 mg/kg diethyl nitrosamine (DEN) over 8 weeks followed by thioacetamide 100 mg/kg (TAA) intraperitoneal injections twice weekly for 15 weeks, treated groups: rats were given canagliflozin (10 and 20 mg/kg b.wt.) orally starting from the 24th week of the experiment till the end of the 29th week. The obtained findings showed that treatment with canagliflozin reduced renal oxidative stress and toxicity indicator levels and considerably reinforced renal antioxidant capacity. The histological changes further supported the biochemical findings. In addition, canagliflozin therapy activated AMPK and inhibited Nrf2, NLRP3 and IL-6/STAT3 pro-inflammatory pathway. Immunohistochemistry exhibited upregulation of pro-apoptotic protein caspase-3 and downregulation of PCNA expression in Cana-treated groups. Conclusion: the results showed that canagliflozin has anti-carcinogenic efficacy against renal carcinogenesis via activating AMPK and suppressing NLRP3/IL-6/STAT3 signaling pathways.