Introduction Tacrolimus is considered an important immunosuppressant for myasthenia gravis (MG); however, patients with MG often use multiple medications concurrently, increasing their risk of interactions with tacrolimus. The present study investigated drug-drug interactions (DDIs) and optimized the initial tacrolimus dosing in patients with MG using population pharmacokinetic (PPK) analysis.Methods Data from patients with MG receiving tacrolimus therapy were retrospectively collected between February 2023 and October 2025 from the Affiliated Hospital of Xuzhou Medical University. Inclusion criteria: (a) Patients with MG, (b) Treatment with tacrolimus, (c) Therapeutic drug monitoring (TDM) for tacrolimus. Exclusion criteria: MG patients with missing clinical medical record data, pregnancy/lactation. Nonlinear mixed-effect modeling (NONMEM) was used to build a PPK model, and the Monte Carlo method was used for simulate tacrolimus concentrations in patients with MG.Results The final model suggested that weight and vitamin D2 soft capsule significantly affected the clearance rate of tacrolimus in patients with MG. When patients with MG were not taking vitamin D2 soft capsules simultaneously, the initial tacrolimus dosing was as follows: for patients weighing 50-78 kg, 0.06 mg/kg was recommended; for patients weighing 78-100 kg, 0.04 mg/kg was recommended. When patients with MG take vitamin D2 soft capsules simultaneously, the initial tacrolimus dosage was as follows: for patients weighing 50-60 kg, 0.10 mg/kg was recommended; for patients weighing 60-100 kg, 0.08 mg/kg was recommended.Discussion Among patients with the same weight, when combined with vitamin D2 soft capsule, the clearance rate of tacrolimus in patients with MG increased by 31%, which was a very interesting finding.Conclusion This study investigated DDIs and optimized the initial dosing of tacrolimus in patients with MG based on PPK analysis and found that when patients with MG take vitamin D2 soft capsule simultaneously, the initial dosages of tacrolimus may need to be increased accordingly.
Introduction: The present study aimed to develop and comprehensively characterize Linezolid (LZD)-loaded Semi-Solid Lipid Nanoparticles (SSLNs) as a potential topical delivery system for wound management. Methods: We prepared SSLN formulations by high-shear homogenization. We characterized the formulations by physicochemical properties, encapsulation efficiency, mechanical and rheological behavior, in vitro release, ex vivo skin diffusion, radiolabeling efficiency, cellular association, and antimicrobial activity. Results: The selected formulation (F11) exhibited a particle size of 437.2 ± 38.7 nm, PDI of 0.425 ± 0.069, zeta potential of −21.8 ± 0.7 mV, encapsulation efficiency of 81.3 ± 2.7%, and a pH of 5.81, together with shear-thinning rheological behavior. In vitro release studies demonstrated sustained drug release compared to the LZD solution. Ex vivo diffusion studies showed gradual, time-dependent permeation, reaching 839.28 μg/cm² at 24 h (68.7% of the applied dose). Radiolabeling with 99ᵐTc achieved an apparent radiolabeling efficiency above 90% under the employed RTLC conditions, and the chromatographic labeling profile was maintained over 6 h. In HaCaT cells, 99ᵐTc-labeled LZD-SSLNs showed significantly higher cell-associated radioactivity (83.80 ± 6.43%-88.41 ± 0.85%) than blank SSLNs (68.81 ± 5.04%-69.37 ± 7.37%). The F11 formulation exhibited antibacterial activity against the tested Gram-positive strains, with inhibition zones of 33 mm (S. aureus), 30 mm (E. faecalis), and 45 mm (B. subtilis), while the blank formulation showed no inhibition. Discussion: The obtained findings indicate that the developed SSLN system provides sustained LZD release and a gradual, time-dependent skin permeation profile while exhibiting greater cell-associated radioactivity than the blank formulation and demonstrating antibacterial activity. Together, the sustained-release and timedependent permeation profiles, the greater cell-associated radioactivity observed for the LZD-loaded formulation, and antibacterial activity support further investigation of the SSLN system for topical delivery applications. Conclusion: Overall, LZD-loaded SSLNs demonstrated sustained release, time-dependent skin permeation, an apparent 99ᵐTc radiolabeling efficiency above 90% under the employed RTLC conditions, greater cellassociated radioactivity than the blank formulation, and antibacterial activity against the tested Gram-positive strains, supporting further investigation of this system for topical wound management.
Introduction/Objective: Cancer comprises heterogeneous diseases driven by genetic and epigenetic alterations that enable uncontrolled proliferation, survival, and metastasis. Drug resistance remains a principal cause of treatment failure and recurrence. This review evaluates nanotherapeutic strategies designed to overcome resistance mechanisms and improve therapeutic outcomes in oncology. Methods: We conducted a narrative synthesis of peer-reviewed literature and clinical data on resistance pathways and nanocarrier platforms. Mechanisms examined include transporter-mediated efflux (P-gp, BCRP, MRP1), enhanced DNA repair, apoptosis evasion, epigenetic reprogramming, and cancer stem cell persistence. Advances in spatial and single-cell profiling informing tumor heterogeneity and microenvironmental influences were integrated. Nanocarrier systems assessed include liposomes, polymeric nanoparticles, dendrimers, and stimuli-responsive platforms. Results: Over two decades, nanomedicines such as Doxi and Onivyde have demonstrated clinical utility in surmounting biological barriers to drug delivery. Targeted nanotherapies enable passive and active targeting, controlled release, and rational combination regimens that mitigate multidrug resistance and enhance selective cytotoxicity. Emerging AI-guided design, tumor microenvironment remodeling, STING pathway activation, and immunogenic cell death induction are accelerating next-generation nano-immunotherapeutics. Discussion: These findings indicate that rational nanocarrier engineering, informed by high-resolution tumor biology, can meaningfully improve drug bioavailability, targeting specificity, and therapeutic index. However, variability in tumor biology, incomplete understanding of nano-bio interactions, and challenges in biomarker discovery, manufacturing scale-up, and regulatory pathways constrain translation. Conclusion: Nanotherapy holds substantial promise for overcoming cancer drug resistance, yet realizing its potential requires interdisciplinary collaboration, mechanism-driven design, and rigorous clinical validation to ensure scalable, biomarker-guided, and regulatory-compliant applications.
Introduction: Tuberculosis (TB) is a transmissible disease caused by Mycobacterium tuberculosis, which continues to be a major public health issue worldwide. The situation has become more alarming with the increasing cases of multidrug-resistant (MDR) strains, which makes treatment difficult. Nitrofurans, a class of heterocyclic compounds known for their antimicrobial potential, have gained renewed attention as scaffolds for anti-TB drug design. This study aimed to investigate the structural features governing the antitubercular activity of 5-nitrofuranyl derivatives using 2D-QSAR modeling and molecular docking analysis and to identify new compounds that inhibit the biosynthesis of the Mycobacterium tuberculosis cell wall. Method: Twenty-eight 5-nitrofuranyl derivatives were studied by means of 2D-QSAR analysis employing descriptors from the Dragon software suite within the framework of CP–MLR methodology. Statistically significant models were selected based on r², Q² (LOO and L5O), and test set predictivity. Molecular docking was performed using AutoDock Vina against Galactofuranosyltransferase 2 (GlfT2), a validated target involved in the cell wall biosynthesis of M. tuberculosis. Result: Robust QSAR models were obtained with up to R² = 0.912 and Q²LOO = 0.839. Key descriptors influencing activity included topological descriptors (IC1, JGI2, JGI5), mass-weighted Burden eigenvalues (BELm2, BELm6), molecular weight (MW), and selected atom-centered fragments such as C-006 and C-031. Docking studies revealed that several compounds (notably 27, 25, and 3) exhibited high binding affinity to GlfT2 (−9 to −6.7 kcal/mol), correlating well with QSAR predictions. Discussion: The obtained QSAR parameters suggested the importance of molecular topology, electronic features, and particular structural fragments in modulating antitubercular activity. Molecular docking to the GlfT2 protein showed that the binding affinity of compounds 27, 25, and 3 was found to be more favorable for their binding in the active site of the enzyme. Moreover, the results from the ADME study demonstrated that compound 3 acquired the best pharmacokinetic properties compared to the other molecules. Conclusion: This integrated QSAR and molecular modeling study highlights the structural determinants of 5- nitrofuranyl-based antituberculosis agents. Compounds with favorable descriptor profiles and strong GlfT2 binding affinity represent promising leads for further development. This approach demonstrates the effectiveness of combining ligand- and structure-based strategies for rational antitubercular drug design.
Introduction/Objective: Opioids remain indispensable analgesics for acute, cancer-related, and selected chronic pain, yet their use is increasingly constrained by the opioid crisis and by opiophobia, an excessive, often irrational fear of opioid prescribing and use. This review synthesises evidence on opioid pharmacology, clinical applications, adverse effects, and opiophobia. Methods: This structured narrative review followed the SANRA criteria; PRISMA and PRISMA-ScR frameworks were not applied. Five databases (Google Scholar, PubMed, Scopus, Web of Science, MEDLINE; 2010-2026) were searched, prioritising systematic reviews, meta-analyses, randomised trials, and guidelines. Sixty-nine sources were synthesised. Results: Opioids act mainly via μ-opioid receptors, suppressing ascending nociceptive transmission and enhancing descending inhibition. Agents differ in potency, onset, duration, metabolism, and adverse-effect profiles. Constipation, nausea, and sedation are common; respiratory depression, although uncommon at titrated doses, is the most serious hazard. Opiophobic attitudes were reported in up to 80.2% of emergency physicians, and up to 64.4% of cancer patients held extreme addiction concerns. The pooled prevalence of opioid use disorder or dependence during long-term opioid therapy for chronic non-cancer pain was 9.3% (95% CI 5.7-14.8%). Discussion: Attitudinal barriers, rather than pharmacological limitations alone, drive undertreatment of pain, and regulatory overcorrection after the opioid crisis has created a secondary burden of inadequate analgesia. Risk stratification, multimodal analgesia, and structured monitoring can limit opioid exposure while preserving effective analgesia. Conclusion: Opioids remain effective and manageable under appropriate supervision. Balanced, evidencebased prescribing frameworks, combined with prescriber and patient education, are essential to reduce harm from both opioid misuse and inadequate analgesia.
