Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) caused by the aberrant attack of the immune system on its own joint tissues. Genetic and environmental factors are the main reasons of immune system impairment and high incidence of RA. Although there are medications on the market that lessen disease activity, there is no known cure for RA, and patients are at risk in varying degrees of systemic immunosuppression. By transporting (encapsulating or surface binding) RA-related self-antigens, nucleic acids, immunomodulators, or cytokines, tolerogenic nanoparticles—also known as immunomodulatory nano-preparations—have the potential to gently regulate local immune responses and ultimately induce antigen-specific immune tolerance. We review the recent advances in immunomodulatory nano-preparations for delivering self-antigen or self-antigen plus immunomodulator, simulating apoptotic cell avatars in vivo, acting as artificial antigen-presenting cells, and based on scaffolds and gels, to provide a reference for developing new immunotherapies for RA.

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease. Activated macrophages in arthritic joints play a prominent role in the initiation and persistence of RA. Despite great progress in the clinical treatment of RA, poor response and high discontinuation due to systemic toxicity remain unsolved issues, especially the well-known methotrexate (MTX). Therefore, active targeted delivery of therapeutic drugs to pathogenic cells in arthritic joints is essential to increase in situ activity and decrease systemic toxicity. Here, we developed an MTX-loaded macrophage-targeted nano-emulsion (NE) based on the over-expression of folate receptor (FR) on activated macrophages, the inherent high affinity of FR for folate (FA), as well as the property of MTX and phospholipids to form complexes (MTX@PC). Intravenous injection of DID-labeled MTX@PC-FA NEs into adjuvant-induced arthritis (AIA) mice, in vivo images and flow cytometry results revealed that the NEs were highly targeted to inflamed joints and macrophages, respectively. Therapeutic studies suggested that this strategy was conducive to achieve high efficacy and low toxicity of MTX in the treatment of RA. Our research highlights MTX@PC-FA NEs as a potential treatment option for RA targeting the FR-expressed activated macrophages.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and joint destruction. Insufficient apoptosis of fibroblast-like synoviocytes (FLSs) significantly contributes to the pathogenesis of RA by promoting hyperplasia and inflammatory cytokine secretion. Celastrol (CLT), a pentacyclic triterpene derived from Tripterygium wilfordii, has shown promise in inducing apoptosis via endoplasmic reticulum (ER) stress-mediated pathways. However, its clinical application is limited by poor solubility and off-target effects. Targeted delivery of CLT to FLSs and their ER could enhance therapeutic efficacy while minimizing toxicity. We engineered CLT-loaded, enzyme-responsive liposomes (CLT-FELipos) functionalized with hyaluronic acid (HA), oligopeptide GPA (for FAP-α recognition on FLSs), an ER-targeting KDEL peptide, and cleavable PEG chains. In vitro, CLT-FELipos were evaluated for FLS-specific uptake (via FAP-α/GPA and CD44/HA interactions), ER accumulation, and apoptosis induction. In vivo, adjuvant-induced arthritis (AIA) rats were treated with various formulations. Joint distribution was assessed using near-infrared imaging, and therapeutic efficacy was evaluated through measurements of paw swelling, histological analysis, and micro-CT for bone erosion. CLT-FELipos demonstrated selective binding to FAP-α on FLSs, followed by PEG cleavage and CD44-mediated cellular uptake. Confocal microscopy confirmed specific accumulation within the ER. In AIA rats, CLT-FELipos showed joint-specific distribution and effectively reduced FLS numbers in arthritic joints. Treatment with CLT-FELipos brought about inflammatory remission, bone erosion repair, and minimal adverse effects. Notably, CLT-FELipos caused minimal systemic toxicity, as evidenced by stable body weight and normal liver and kidney function tests results. CLT-FELipos represents a novel drug delivery system that specifically targets FLS and ER, which enhances CLT's therapeutic index in RA by inducing apoptosis in hyperplastic FLSs. The dual-targeting strategy (FAP-α/CD44 for FLSs and KDEL for ER) ensures precise drug delivery while reducing inflammation and joint destruction with improved safety. This innovative approach holds potential for RA treatment and warrants further clinical investigation.

Introduction: Antimicrobial Stewardship programs are crucial for reducing overall antibiotic consumption, but in practice, there are often issues with unclear responsibilities and ambiguous tasks. Pharmacists play a critical role in AMS due to their combined management functions and professional expertise.Objective: To investigate the impact of a Pharmacist-Driven Antimicrobial Stewardship program on the consumption of antibiotics in a hospital.Methods: Under the support of a hospital top-level design, we implemented a Pharmacist-Driven Antimicrobial Stewardship program led by pharmacists and involving multiple disciplines. The program focused on revising the antibiotic formulary and optimizing key points of antibiotic management, using the inpatient Antibiotic Use Density as the core control indicator. This was conducted through three phases: program initiation, implementation, monitoring and control. Clinical pharmacists ensured the long-term operational quality of the program. We evaluated the impact of the program on relevant indicators of antimicrobial consumption in inpatient.Results: Compared to the pre-implementation year of 2020, the annual Antibiotic Use Density for inpatients across the hospital decreased by 22.28% in 2024, reaching 36.26 defined daily doses/100 patient days. Additionally, the monthly inpatient Antibiotic Use Density in 2024 was significantly reduced (p < 0.001), along with the antibiotic usage rate (p < 0.05), expenditure on antibiotics per inpatient (p < 0.001), and the proportion of antibiotic expenditure relative to total for inpatients (p < 0.001). The rational use of antimicrobial agents in inpatient wards has been enhanced. Through targeted management, some antibiotics showed trends of increased or decreased usage. The detection rates of Methicillin-Resistant Staphylococcus aureus and Extended-spectrum β-lactamase-producing Escherichia coli did not show a significant decrease.Conclusion: The Pharmacist-Driven Antimicrobial Stewardship program effectively leveraged the managerial roles and professional skills of pharmacists in rational drug use management, resulting in a significant reduction in hospital antibiotic consumption. However, to further validate its effectiveness in reversing bacterial resistance, the program requires longer-term operation and could be considered for regional expansion.

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production. Aim: The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2. Methods: A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model. Results: Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN. Conclusion: NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.

Objective: To explore the current status of therapeutic drug monitoring (TDM) research on anticancer drugs, analyze research hotspots and trends, and provide insights and references for future studies. Methods: Data were retrieved from the Web of Science Core Collection (1990–2024) using keywords related to “anticancer drugs” and “therapeutic drug monitoring.” Bibliometric analyses were performed using VOSviewer, CiteSpace, R, and Scimago Graphica to visualize trends in publications, keywords, collaborations, and citation networks. Results: A total of 1474 articles were included. Global research output on TDM for anticancer drugs has grown steadily, with an accelerating trend in recent years. Key research themes include drug-specific monitoring, analytical methodologies, and clinical safety and efficacy. Busulfan remains the most studied agent in hematologic malignancies, while tyrosine kinase inhibitors, particularly crizotinib and nilotinib, along with monoclonal antibodies, have emerged as focal points of recent citation bursts. The keyword “pediatric patients” also shows a strong burst signal, reflecting growing attention to developmental pharmacokinetics and individualized dosing in vulnerable populations. The majority of influential studies were published in clinical oncology and pharmacology journals, with chemotherapy and targeted therapy dominating among the most cited papers. The United States, China, Japan, and Western European countries, notably the Netherlands and France, account for the majority of global publications. Among these, the Netherlands, Switzerland, and France demonstrate not only the highest research intensity, as measured by the Relative Importance Index (RII), but also a gradual increase in RII over time. Institutional-level RII analysis further highlights sustained contributions from leading European academic and clinical networks. International collaboration is highly concentrated among these high-output regions, forming a tightly interconnected research network. Conclusion: This study maps the evolving landscape of TDM in oncology. Accelerating research on tyrosine kinase inhibitors, monoclonal antibodies, and pediatric populations highlights TDM’s clinical value in optimizing therapy for narrow-therapeutic-index drugs. Rising research intensity in Europe and strong international collaboration underscore a coordinated global effort, supporting TDM’s integration into precision oncology, especially for vulnerable patients.