Engineering polyamidoamine dendrimer nanoparticles for targeted drug delivery to proximal tubular cells after renal ischemia/reperfusion injury.

Ultrasound-responsive nanocarriers for cancer therapy: Physiochemical features-directed design.

Interstitial drug delivery system: Physiological basis and (pre)clinical progress.

Balancing oral sequential absorption barriers of semaglutide-loaded nanoparticles by optimization of surface glycocholic acid density.

Music enhances lipid nanoparticle brain delivery and mRNA transfection in brain cells.

Novel single-domain antibodies targeting a unique transferrin receptor 1 epitope for cross-species delivery of drugs in the central nervous system.

Targeting post-extraction complications with functional hydrogels: Mechanistic insights, translational strategies, and clinical prospects.

Toward intelligent immune microneedles: Strategies for sensing, therapy, and immune regulation.

Precisely targeting of engineered nanovesicles to implanted scaffolds via click chemistry for microenvironment regulation in acute spinal cord injury.

Intraocular fate of surface charge-dependent nanomicelles via topical administration: Posterior delivery and transport pathway.

Nasal-to-brain siRNA delivery based on trace amine associated receptor for improving cognitive function.

Polymeric materials have become important components in prefilled syringes, drug delivery systems, and advanced medical devices. Background/Objectives: Nitrogen dioxide gas is used for the terminal sterilization of drug delivery systems. For the implementation of sterilization methods, compatibility with materials must be demonstrated such that the materials maintain product requirements and specifications after sterilization and at the time of use (i.e., product shelf life). Methods: Commonly used polymers were selected based on their chemical structures to provide insight into the nature of reactions that occur at the temperature and NO2 concentration levels used in the sterilization process. After exposure to the NO2 process, materials were evaluated for chemical, mechanical, and biocompatibility properties. Results: In this paper, we demonstrated the compatibility of polymers comprising carbonyl, unsaturated ester, and ketone groups which have been used in medical devices sterilized with NO2. No significant chemical or physical changes were observed upon the treatment of Amorphous Polyester, Polysulfone (PSU), Polycarbonate (PC), PolyEtherEtherKetone (PEEK), PolyArylEtherKetone (PAEK), and Polypropylene (PP) with NO2 at a sterilization temperature of 20 °C. At this relatively low sterilization temperature, the reactions of NO2 with the polymer do not typically occur because the activation energies of these reactions require much higher temperatures. Conclusions: Not all materials will be compatible with NO2 sterilization, and even with the established data, many devices will need to have their polymers evaluated for compatibility before moving to NO2 sterilization. These results will provide guidance to device designers selecting materials for new drug delivery devices and to regulators that review the safety and efficacy of these devices.

Gold nanoparticles have long been explored for their potential in medical diagnostics, drug delivery, and imaging, particularly in oncology. However, successful translation to clinical applications requires a deep understanding of their biomolecular interactions and transport mechanisms across cellular barriers and within cells. In this review, we examine the current understanding of the journey of gold nanoparticles from systemic administration to tumour infiltration. Specific focus is placed on the biological barriers crossed and the mechanisms involved in traversing those barriers, including active and selective transport pathways, like transcytosis, increasingly recognised as critical for nanoparticle translocation across endothelial and tumour barriers. We stratify the nanoparticle journey into smaller stages and critically discuss the most relevant in vitro models used to study each stage in isolation. Although traditional 2D cell cultures have provided some fundamental insights, more advanced tissue culture models outlined in this review offer enhanced physiological relevance. Monitoring nanoparticle behaviour within these models cannot be achieved without sophisticated imaging and quantification techniques. Herein, we have identified the most appropriate detection methods and their suitability for being used on each in vitro model for the detection of label-free gold nanoparticles. Using label-free nanoparticles preserves their native physicochemical properties and avoids potential artefacts introduced by fluorescent or radioactive tags, and conveniently, gold lends itself well to label-free detection due to its unique optical and electronic properties. By integrating insights from advanced in vitro modelling and cutting-edge detection strategies, this review highlights the current landscape and future directions for optimising the study of gold nanoparticle delivery across barriers in cancer nanomedicine.

Molecular metal-oxo nanoclusters with tunable redox and structural properties have emerged as powerful bio-inorganic tools in catalysis, protein crystallization, and therapeutic applications. Despite their potential, interactions between discrete clusters and proteins are predominantly driven by nonspecific intermolecular interactions, which limit precise control over binding sites and functional outcomes. In this work, we introduce a new strategy to achieve site-directed binding of vanadium-based polyoxometalate clusters (POVs) to distinct regions of Hen Egg White Lysozyme (HEWL), an archetypal antimicrobial enzyme. Three novel hybrid POVs were designed and fully characterized, starting from an azide-functionalized cluster (Na-V6-N3), which was subsequently post-functionalized with a hydrophobic hexyne group (Na-V6-Hex) to probe nonpolar interactions, and α-d-mannopyranoside (Na-V6-Man) to mimic the protein's natural substrate. Structural and spectroscopic analyses demonstrated that, in contrast to conventional nonhybrid POV clusters which bind nonspecifically to peripheral positively charged protein patches, the hybrid POVs achieve distinct binding behaviors. Specifically, Na-V6-N3 and Na-V6-Man selectively target the glycosidic pocket, resembling the binding of the protein's natural substrate, while Na-V6-Hex exhibits an unprecedented crystallization of two POV clusters in close proximity, which wrap around the protein surface. These findings highlight that strategic organic functionalization can circumvent electrostatic barriers to achieve site-selective cluster-protein interactions, thus opening new avenues for the application of metal-oxo clusters in biotechnology, drug delivery, and medicine.

Peripheral artery disease (PAD) is a disease of both atherosclerotic and thromboembolic pathology, affecting more than 230 million people globally. PAD patients are at an increased risk of thrombotic events and often require lifelong antithrombotic therapy. Thromboembolism can lead to complete occlusion of affected arteries and put patients at risk for critical limb threatening ischemia (CTLI). PAD blockages are cleared using drug-eluting stents (DES) and drug-coated balloons (DCB). However, PAD treatment below the knee (BTK) presents unique challenges. While DCB are frequently used to treat BTK disease, no DCB has gained FDA approval for this indication. However, innovation in the field has produced drug delivery systems and formulations that may yet enhance the effectiveness of these therapies. In this review, we will provide a brief overview of the pathological mechanisms associated with PAD and review the materials and drugs frequently used in DCBs with an emphasis on excipients and drug carriers. Finally, we will highlight emerging devices undergoing clinical trials to treat BTK disease and how they differ from their predecessors.

Cyclodextrin-based drug delivery systems provide a robust platform for designing targeted nanocarriers that efficiently encapsulate, stabilize, and deliver poorly soluble drugs to specific sites. Their unique ability to form host - guest complexes and construct supramolecular networks adorned with tailored ligands allows precise targeting of diseased areas, thereby enhancing therapeutic efficacy while minimizing systemic side effects. This review provides an overview of recent advances in cyclodextrin-based carriers for targeted drug delivery. It examines a wide array of ligand-functionalized systems, from conjugates and assemblies to branched polymers and nanosponges, organized according to their target organs, including the brain, eyes, lungs, gastrointestinal tract, liver, and breast. The discussion is grounded in an extensive literature search, highlighting strategies such as the incorporation of active targeting ligands, stimuli-responsive release mechanisms, and dual-function theragnostic platforms. Although cyclodextrin-based systems have demonstrated promising improvements in drug solubility, stability, and target specificity, challenges remain with regard to overcoming biological barriers and minimizing off-target effects. The authors believe that continued optimization of carrier design, combined with advances in targeting and stimuli-responsive technologies, will be crucial for translating these innovative systems into effective clinical therapies.

Retinal neovascular diseases, a leading cause of blindness, can be treated with intravitreal tyrosine kinase inhibitors (TKIs). Injectable intravitreal depots capable of sustained TKI release for more than 6 months are highly desirable. While existing platforms utilize covalently cross-linked hydrogels for prolonged release, thermoreversible hydrogels with good injectability have been deemed unsuitable for long-duration drug delivery due to rapid erosion from weak physical cross-linking. Here, we report the first injectable supramolecular hydrogel capable of 1-year sustained TKI release, prepared by codissolving an amphiphilic thermogel with the TKI. This hydrogel achieved a 12-fold longer drug-release duration compared to commercial Pluronic-F127 thermogel, arising from strong polymer-drug interactions resulting in a distinct gel microstructure and enhanced persistence. The released TKI retained bioactivity after one year, successfully resolving choroidal neovascularization (CNV) lesions in murine models. Our findings highlight the potential of supramolecular hydrogels for ultralong drug delivery to the retina.

Atrial fibrillation (AF), the most common form of cardiac arrhythmia, is closely associated with atrial fibrosis and electrophysiological remodeling, both of which contribute to its persistence and recurrence. Current treatment strategies remain limited in effectiveness and safety, highlighting the need for novel therapeutic approaches. Nanocarrier-mediated delivery systems represent a promising approach, enabling targeted delivery of drugs and genes to modulate fibrotic pathways and restore electrical homeostasis. The review examines the molecular mechanisms driving AF-related fibrosis, including dysregulation of the TGF-β/Smad and Wnt/β-catenin signaling cascades, as well as the influence of neuro-cardiac interactions, lipid metabolism abnormalities, and oxidative stress. We systematically evaluate nanocarriers, such as lipid nanoparticles (LNPs), polymeric systems (PLGA/PEG), and metal-based nanomaterials (AuNPs, AgNPs), to enhance cardiac targeting, prolong circulation, and mitigate off-target effects. Notably, CRISPR-Cas9-loaded nanoparticles and siRNA/mRNA delivery systems demonstrate efficacy in suppressing extracellular matrix deposition and restoring connexin 43-mediated electrical coupling. In addition, stem cell-derived extracellular vesicles (EVs) integrated with nanocarriers provide cell-free therapeutic options for myocardial repair. Key challenges, including biocompatibility, delivery precision, and long-term biosafety, are critically discussed, alongside emerging research directions involving artificial intelligence-guided nanodrug design and hybrid systems combining bioelectronic interfaces with nanoscale platforms. The integration of nanobiotechnology with molecular cardiology offers a path toward precision nanomedicine, enabling mechanism-based interventions that may transform the prevention and treatment of AF and facilitate the translation of preclinical advances into clinical application.

The worst of the COVID-19 (coronavirus disease 2019) pandemic may be over, but its impact continues to be felt worldwide. During the outbreak, medical regulatory authorities introduced several principles for outbreak control, with the World Health Organization emphasizing three key strategies: prevention, early detection, and treatment. In this context, technological advancements have played a critical role, particularly nanotechnology, which has emerged as a promising platform for medical innovation. Its applications span multiple sectors, including healthcare, environmental protection, and diagnostics. These applications offer unmatched potential to enhance personal protective equipment, develop antiviral surface coatings, and engineer rapid point-of-care diagnostics. Nanotechnology contributed significantly to combating COVID-19, enhancing prevention through nanofiber-enhanced masks and nanoparticle-based disinfectants; facilitating diagnosis via gold nanoparticles (AuNPs) and magnetic nanoparticle biosensors, quantum dots, and artificial intelligence-integrated nanosensors; and supporting treatment efforts through lipid nanoparticle (LNP) vaccines, virus-like particles, and targeted drug delivery systems. We highlight key nanomaterials such as silver nanoparticles, copper nanoparticles, AuNPs, zinc oxide nanoparticles, and selenium nanoparticles, alongside advanced formulations like LNPs and polymeric nanocarriers, exploring their mechanisms of viral inactivation, sensitive detection, and controlled delivery of therapeutics. Furthermore, this review addresses critical regulatory and translational challenges and post-pandemic adaptations of nanotechnologies for emerging viral threats.

Delivery of therapeutics to the middle and inner ear for the treatment of various otological pathologies is often inefficient using conventional methods. Systemic treatments may fail to reach therapeutically effective concentrations at the target site and can result in off-target effects, while local treatments typically require invasive methods such as intratympanic injections due to low tympanic membrane (TM) permeability. In this study, a series of TM transpermeation devices for topical delivery of ototherapeutics were designed, prototyped, and characterized. The devices were generated via high-precision, 2-photon polymerization 3D printing and feature tailorable tissue residence times achieved by varying design features and materials. Type 1 devices, manufactured from hyaluronic acid, rapidly dissolve after generating an initial TM perforation and should allow for quick healing and short-term treatments (several days). Type 2 and 3 devices, two variants of the same design which were either directly printed with a biocompatible photoresin or cast from poly(lactic acid), are more stable and intended for slightly longer treatments (weeks). Finally, Type 4 and 5 feature nondegrading materials and barbed designs which should significantly increase their residence time for long-term, repeat-dosing drug treatments (months). Results show that all the devices effectively insert into TM tissue analogs with minimal force. Devices applied to in vitro TM tissue models showed no tissue toxicity and substantially increased drug permeation. Finally, in-silico modeling was used to predict minimal to no expected impact on hearing. Together, this work introduces a new concept for increasing the efficacy of topical ototherapeutic delivery which could improve patient outcomes and compliance over current methods.