tolterodine (Detrol LA / Detrusitol Neo / Detrusitol Retard)

On-demand design of controlled-release systems using an expert-mimic AI framework.

Qin Ying Y, Zhou Rushuang R, Ming Yali Y, Li Bohao B et al.

Navigating a vast formulation-preparation design space that is highly sensitive to perturbations makes trial-and-error approaches inefficient and costly for diverse clinical needs. Here, we introduce an expert-mimic AI framework called E-MAF that integrates a process-aware surrogate with an optimized genetic algorithm to emulate coarse-to-fine reasoning, autonomously generating lab-ready designs tailored to desired release profiles. We show that E-MAF delivers on-demand release and shortens design cycles from 6-12 months to approximately 1 hour. We demonstrate that in vitro release, in vivo pharmacokinetics and therapeutic effects match or surpass commercial benchmarks across 7 active pharmaceutical ingredients. We show that E-MAF also enables release profiles that are hard to achieve by conventional approaches, exemplified by ≤2% risperidone burst within 1 h and near-zero-order release over ~28 days in vivo. These results demonstrate E-MAF's potential to accelerate polymeric controlled-release system development and drug-delivery industrialization.

Emerging therapies for knee osteoarthritis.

Courties Alice A, Winkler Tobias T, Conaghan Philip G PG, Berenbaum Francis F

Knee osteoarthritis (OA) is the most prevalent form of OA and a leading cause of chronic pain and disability worldwide. Its growing burden, driven mainly by ageing and obesity, is associated with major societal costs and increased cardiovascular mortality. Knee OA is now recognized as a heterogeneous whole-joint disease involving biomechanical, metabolic, inflammatory, osteochondral and neurovascular mechanisms. This complexity helps to explain why existing analgesics have modest efficacy and why disease-modifying OA drug development has repeatedly faltered. The therapeutic landscape is nevertheless evolving rapidly. Emerging symptomatic strategies include incretin-based therapies (semaglutide is the first to show substantial benefits for pain and function), neurotrophin modulation, extended-release intra-articular glucocorticoids, lubricating injectables and image-guided neurovascular interventions. In parallel, candidate disease-modifying OA drugs target cartilage anabolism, Wnt signalling, matrix-degrading enzymes, subchondral bone remodelling, immunometabolic pathways and local gene therapy. Several treatments, including locally administered GLP1 receptor agonists, the anabolic agent TPX-100 and intra-articular IL-1 receptor antagonist gene therapy, have shown encouraging signals, whereas mesenchymal stromal cell therapies have thus far demonstrated inconsistent efficacy across phase III clinical trials, highlighting the need for further standardization of mesenchymal stromal cell products and optimization of patient selection. Recent advances signal a shift towards a more diverse therapeutic landscape for knee OA, with emerging opportunities to target both symptoms and the underlying mechanisms of disease.

Extended Dual Antiplatelet Therapy Versus Aspirin Monotherapy After Drug-Eluting Stent Implantation: A Systematic Review and Meta-Analysis With GRADE Evaluation and Trial Sequential Analysis.

Ali Muhammad Abdullah MA, Nawaz Adil A, Sethi Furqan Ahmad FA, Alam Umama U et al.

The optimal duration of dual antiplatelet therapy (DAPT) following drug-eluting stent implantation remains uncertain. We evaluated extended DAPT versus aspirin monotherapy in patients who completed approximately 12 months of uneventful DAPT after percutaneous coronary intervention. PubMed, Embase, and Web of Science were searched through August 2026 for randomized controlled trials comparing these strategies. The primary outcome was myocardial infarction (MI); secondary outcomes included all-cause mortality, cardiac death, stent thrombosis, repeat revascularization, stroke, and clinically relevant bleeding (Bleeding Academic Research Consortium type 2-5). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a Mantel-Haenszel random-effects model. Certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE), and trial sequential analysis was performed for MI. Six trials involving 28,601 patients were included. Extended DAPT significantly reduced MI compared with aspirin monotherapy (RR, 0.66; 95% CI, 0.51-0.85; P = 0.001; I2 = 37%). No significant differences were observed in all-cause mortality, cardiac death, stent thrombosis, repeat revascularization, or stroke. Clinically relevant bleeding was also not significantly different (RR, 1.19; 95% CI, 0.66-2.15; P = 0.56), although substantial heterogeneity was observed (I2 = 87%) and certainty was low. GRADE certainty was high for MI, cardiac death, and repeat revascularization; moderate for all-cause mortality; and low for stent thrombosis and bleeding. Trial sequential analysis for MI crossed the conventional significance boundary but not the trial sequential monitoring boundary or required information size. Extended DAPT may reduce MI, but individualized assessment of ischemic and bleeding risk remains important, and further adequately powered trials are warranted.

Binding-To-Release Enhances Efficacy of Small Molecule-Drug Conjugates.