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Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, largely due to its dense stromal architecture and poor intratumoral drug penetration. To address this challenge, IMP305 was developed as an ultrasound-sensitive liposome for tumor-localized drug release. In particular, IMP305 is dominantly capable of release by ultrasound-mediated cavitation. Methods: This ultrasound-sensitive liposome integrates tumor-specific drug delivery with cavitation-induced loosening of the stromal architecture in PDAC, thereby enabling more efficient intratumoral drug release using PANC-1 xenografted mouse. Results: The maximal tolerance dose of exatecan was increased by encapsulation into IMP305. Cavitation-triggered structural disruption of IMP305 was 84.68 ± 6.21%, which resulted in a robust release of approximately 84.4 ± 1.95% of the encapsulated exatecan. In PANC-1 xenograft models, IMP305 exhibited a maximal tolerance dose approximately four times higher than that of free exatecan and demonstrated markedly superior antitumor ability. Especially, IMP305 combined with focused ultrasound achieved the most pronounced therapeutic benefit, demonstrating a 49.17 ± 9.00% reduction in tumor volume at day 48 and an 80% survival rate at day 60. Conclusions: In conclusion, these findings demonstrate that ultrasound-activated IMP305 significantly enhances intratumoral accumulation and release of exatecan, resulting in superior tumor suppression while mitigating systemic toxicity. Full article

Spray freeze-drying (SFD) is a novel technique for formulating dry powders, particularly for pulmonary drug delivery via dry powder inhalers (DPIs). Despite their low density and excellent aerodynamic properties, such powders are affected by high cohesiveness due to their surface properties. Sugars such as mannitol (MAN), trehalose, raffinose, and sucrose are commonly used in SFD. MAN is widely employed due to its high MAN—ice eutectic temperature—at which MAN and water (ice) form a stable eutectic mixture—and its crystallinity. However, crystallinity can impact the microparticles’ (MPs) cohesiveness, since MAN exhibits distinct polymorphs (α, β, δ) with peculiar properties. This study provides valuable insights for the development of DPI formulations by ensuring precise control over MAN polymorphism, ultimately enhancing formulation stability and performance. We introduced, for the first time, an intermediate freezing (IF) step within the SFD process to modulate MAN polymorphism, demonstrating its synergy with optimised storage temperature conditions. Furthermore, polyvinylpyrrolidone, 2-hydroxypropyl beta cyclodextrin, dextran, and polysorbate 80 were employed as polymorphism-controlling agents for MAN, contributing to the development of stable formulations with reduced particle cohesion and improved storage stability at room temperature. For the first time, this study shows that MAN polymorphism in SFD can be controlled to drive dry powder inhaler performance. Full article

Gallium-based liquid metals have been extensively studied in the field of biomedical engineering, including applications in tumor and inflammatory disease therapy, as well as targeted drug delivery. Among these, leveraging the photothermal effect of gallium liquid metals enables effective treatment of heat-sensitive cells in tumor regions and enhances the diffusion capability of liquid metal microdroplets. However, research on the active treatment of ulcerative colitis (UC) using photothermal therapy with liquid metals remains unexplored. This study focuses on constructing an active composite colloidal motor based on gallium indium liquid metal alloy, using liquid metal microdroplets as the core. Through layer-by-layer assembly of polyelectrolytes, a liquid metal active droplet loaded with the drug mesalazine (5-aminosalicylic acid), named as LMAD-A was developed. Under asymmetric light fields generated by NIR-II light source irradiation, LMAD-A exhibits autonomous locomotion, achieving an effective diffusion coefficient more than 800 times greater than that of Brownian motion in liquid metal microdroplets of similar size. Furthermore, LMAD-A demonstrates phototactic behavior, moving toward the NIR light source autonomously. Through in vitro and in vivo experiments in mice, it was verified that LMAD-A can aggregate, deform, and fuse in the mouse colon under photothermal effects, leading to enhanced release of the loaded drug. In simulated treatments, LMAD-A significantly alleviated DSS-induced colitis in mice, confirming the targeted therapeutic capability of active liquid metal microdroplets as an active therapeutic agent in UC-affected regions. Full article

Swellable microparticles are a promising strategy for pulmonary drug delivery. They provide good aerosol performance in the dry state and enlarge after deposition in the lungs. In this study, we aimed to develop and characterize spray-dried microparticles composed of carboxymethyl chitosan (CMC), L-leucine, and suramin, a hydrophilic polyanionic drug. Microparticles were obtained by co-spray drying (Co-SD) formulations with increasing leucine content (0–10% w/w) and evaluated for morphology, thermal behavior, crystallinity, swelling, aerodynamic deposition using a Next Generation Impactor (NGI), and cytocompatibility in pulmonary epithelial cells. The 10% leucine formulation produced the highest fine particle fraction (35.2 ± 1.1%) and the lowest mass median aerodynamic diameter (1.0 ± 0.4 µm). These values indicate efficient in vitro deep lung deposition. XRPD and DSC showed that the Co-SD formulations were predominantly amorphous. Hydration studies revealed rapid water uptake and a clear increase in particle size, leading to the formation of swollen microgels. Cell viability assays demonstrated >85% viability up to 100 µM suramin, suggesting that CMC–leucine microgels enable efficient pulmonary delivery of hydrophilic drugs by combining respirable dry-state properties with in situ swelling and reducing immunological clearance. Future in vivo studies will be needed to assess long-term stability, macrophage interaction, and the translational potential of this delivery system. Full article

Carbon dots have emerged as promising nanocarriers for drug delivery due to their unique physicochemical properties and biocompatibilities. Here, the potential of leaf-derived carbon dots (named as SBL_CD), derived from Seabuckthorn (Hippophae rhamnoides L.), was illustrated as a novel nano-formulation for bioactive compound delivery. Seabuckthorn leaves, rich in flavonoids, are the waste product during the production of Seabuckthorn fruits. The wasted leaves were utilized to synthesize carbon dots via a hydrothermal method. The resulting SBL_CD, characterized by TEM, FT-IR and Raman spectroscopy, exhibited a diameter of ~5 nm in both amorphous and quasi-crystalline forms. Applications of SBL_CD in cultures demonstrated robust properties of anti-inflammation and inducing neuronal cell differentiation. Furthermore, SBL_CD was able to encapsulate luteolin, a bioactive flavonoid. The enhanced delivery efficiency translated to superior biological activity, with SBL_CD-luteolin requiring only 1.50 μg/mL in achieving the EC₅₀ efficacy, as compared to 6.82 μg/mL for free luteolin in pNF200-Luc expression assays. This approach not only valorizes Seabuckthorn leaf by-products but also potentially improves the efficacy of encapsulated flavonoids. The development of SBL_CD as a multifunctional platform for flavonoid delivery represents a promising strategy in enhancing the efficacy of neuroactive compounds, combining anti-inflammatory effects (>70% cytokine suppression) with enhanced cellular uptake (4.5-fold increase). Full article

Ceftobiprole is a novel and promising antibiotic; however, the direct pharmacological use of its native form is limited by its low water solubility. The first part of this study provides a deeper insight into the physicochemical properties of this drug. One- and two-dimensional nuclear magnetic resonance (NMR) spectra in D₂O were recorded, and a complete assignment of ¹H and ¹³C signals was achieved with the support of quantum mechanical calculations. The combined results from capillary electrophoresis and NMR confirmed the cationic nature of ceftobiprole at pH values well below 3 and the protonation of the secondary amino group, thus supporting the theoretically predicted dominant protonation states. Molecular dynamics simulations revealed that zwitterionic ceftobiprole molecules associate through hydrogen bonding, whereas in the cationic form, the attractive forces involve weaker π-π and stacking interactions. The use of ceftobiprole in its native form in pharmaceutical formulations was made possible through the development of a novel freeze-dried cyclodextrin-based delivery system. Consequently, the second part of this article focuses on evaluating the biological properties of this system (ceftobiprole/maleic acid/sulfobutylether-β-cyclodextrin in a molar ratio of 1:25:4), including its antibacterial activity against the most common pneumonia-causing pathogens and its cytotoxicity towards normal and cancer cells. Full article

This research successfully developed novel hydrogels composed of methacrylated dextran and inulin for targeted drug delivery in colorectal cancer therapy. The formulation exploits the natural degradation of both biopolymers by the large intestine’s microflora. A key achievement was the development of a room-temperature free radical polymerization synthesis method. The study thoroughly investigated how varying inulin content (10 and 20 wt%) influenced the hydrogels’ properties. The formulation with 20 wt% inulin exhibited the highest swelling ability at both pH 3 and pH 6, and consequently the lowest elastic modulus, measured by a newly established technique for granulated hydrogels. Using uracil as a model drug, in situ incorporated, confirmed that the greatest drug release occurs in the colorectal region for the neat dextran-based hydrogel, triggered by specific microbial enzymes. Notably, the addition of inulin did not enhance biodegradation-driven drug release in combination with dextran; instead, inulin primarily acted as a protective component against premature hydrolysis in the gastric medium. These findings strongly confirm that the targeted action is predominantly governed by the dextran component. The synthesized hydrogels, particularly the dextran-only formulation, therefore show strong potential as effective carriers for colon-targeted drug delivery. The primary objective of this study was to evaluate the feasibility of modified and unmodified dextran and inulin as biodegradable carriers for enzyme-triggered, colon-targeted drug delivery. Full article

Skin scars represent a complex therapeutic challenge, with significant functional, aesthetic, and psychological implications. Despite advances in laser therapy, monotherapy has significant limitations, particularly for patients with complex scars with atrophic, hypertrophic, vascular, and pigmentary components. The combined use of multiple laser sources, in sequential or simultaneous mode, allows for the selective targeting of specific tissue components and improves clinical efficacy while maintaining a good safety profile. This narrative review critically analyses the available evidence on combination therapies for atrophic, hypertrophic, keloid, and post-surgical and burn scars. Protocols combining ablative lasers (CO₂, Er:YAG), non-ablative lasers (1540–1550 nm), vascular lasers (PDL, Nd:YAG) and intense pulsed light (IPL) are reported. Possible integrations with adjuvant techniques, such as radiofrequency, platelet-rich plasma (PRP), and laser-assisted drug delivery, are also mentioned as areas for future development. The available data suggest a promising role for multimodal strategies, but the literature remains limited by small cohorts, heterogeneous protocols, and short follow-up periods. Although adverse events are generally mild and transient, typically involving erythema, oedema, or temporary dyschromia, an awareness of safety considerations remains essential, particularly in higher phototypes and when using ablative modalities. Further prospective and multicentre studies are needed to define standardised protocols and consolidate the role of combination therapies in the management of scars. Full article

Lipid-based nanomedicines are already widely used in antitumor therapy and gene delivery. However, their complex structural features demand advanced mesoscopic structural characterization tools for effective research and development (R&D) and quality control. Synchrotron small-angle X-ray scattering (SAXS) is a powerful, non-invasive technique for probing nanoscale membrane organizations, monitoring in situ dynamic membrane assembly, and exploring the interactions of components in lipid-based drug delivery systems, including liposomes, lipoplexes, lipid nanoparticles (LNPs), and lyotropic liquid crystals (LLCs). Recent advances in high-flux synchrotron facilities, high-frequency detectors, and automated SAXS data processing pipelines permit a detailed structural characterization of lamellarity, bilayer spacing, internal phases, core–shell morphology, as well as “pump-probe” dynamic process studies for lipid nanomedicines. Though major challenges remain in sample polydispersity and model fitting, the advances in time-resolved synchrotron SAXS, high-throughput automation, and artificial intelligence (AI)-assisted modeling are rapidly reducing this barrier. This review summarizes SAXS methodology and introduces representative case studies in the field of lipid nanomedicines. The performance of BioSAXS beamline BL19U2 in the Shanghai synchrotron radiation facility (SSRF) and prospects of AI-guided drug screening at BL19U2 are highlighted to advance intelligent R&D and quality control for lipid nanomedicines. Full article

Tea polyphenols (TP) offer health benefits, but their stability is compromised by sensitivity to environmental factors, limiting their applications. Developing stimulus-responsive delivery systems that precisely control TP release is essential. This study prepared novel hydrogel beads encompassing carboxymethyl chitosan (CMC), sodium alginate (SA), and MXene (Ti₃C₂T_x) using a blending method for the sustained release of TP. After being exposed to 808 nm near-infrared (NIR) radiation, the beads demonstrated excellent stability in simulated gastric conditions, resulting from the pH-dependent solubilization, facilitating controlled TP release under simulated intestinal conditions. The drug release kinetics conformed to the Ritger–Peppas model. Notably, CMC-SA-MXene@TP exhibited strong antioxidant activity and antimicrobial properties, effectively inhibiting the growth of S. aureus (ATCC 6538) and E. coli (ATCC 25922). Additionally, according to in vitro cellular assays, they exhibited good biocompatibility with normal liver cells (HL-7702) and could effectively inhibit hepatocellular carcinoma cells (HepG2). These hydrogel beads, featuring excellent pH and NIR responsiveness, biocompatibility, drug loading efficiency, antioxidant capability, and antibacterial activity, represent promising candidates for advanced wound dressings or oral drug delivery systems for modulating intestinal flora. Full article

The characterization and biomedical modification of bentonite clays from the Kalzhat deposit (Kzh), which is situated in Kazakhstan’s Zhetysu region, are the main objectives of this work. In order to improve the raw material’s structural qualities, the montmorillonite fraction was enriched, and coarse impurities were eliminated using the Salo method. The presence of meso- and micropores that guarantee high dispersity and specific surface area, as well as the prevalence of montmorillonite and kaolinite, was all confirmed by physicochemical analysis. Particle size measurements indicated finely dispersed structures with a propensity to aggregate, whereas thermal analysis demonstrated resilience under heating. After effective functionalization with silver nanoparticles, a porous hybrid system with improved surface reactivity was produced. These enhancements demonstrate the modified bentonite’s usefulness as a multifunctional carrier for the immobilization and controlled release of pharmaceuticals, with potential uses in drug delivery systems, antimicrobial coatings, and wound-healing materials. The material has potential use in sorption and environmental protection technologies in addition to its biomedical application. Overall, Kzh’s structural and functional performance is greatly improved by the combination of purification and functionalization with silver nanoparticles, highlighting its promise as a useful element in the development of next-generation polymer–composite systems. Full article

Brain aging is a progressive process marked by cellular dysfunction, chronic inflammation, and increased susceptibility to neurodegenerative diseases. A growing body of evidence identifies cellular senescence, the accumulation of non-dividing, metabolically active cells with a pro-inflammatory secretory profile (SASP), as a key contributor to cognitive decline and brain aging. This review explores the emerging field of senotherapeutics, which includes senolytics (agents that eliminate senescent cells) and senomorphics (agents that suppress SASP without killing cells), as potential strategies to manage brain aging. We summarize recent preclinical studies demonstrating that senotherapeutics can reduce neuro-inflammation, improve synaptic plasticity, and enhance cognitive function in aged animal models. Additionally, we highlight early-phase clinical trials investigating senolytic compounds in Alzheimer’s disease and discuss key challenges, including the delivery of drugs to the brain, biomarker development, and long-term safety. The review concludes that senotherapeutics, particularly when combined with personalized and multimodal approaches, represent a promising avenue for mitigating age-related cognitive decline and promoting healthy brain aging. Full article

Breast cancer is one of the most prevalent malignant tumors worldwide, with the highest incidence and mortality among women. Early precise diagnosis and the development of efficient treatment regimens remain major clinical challenges. Harnessing the programmable size, surface chemistry, and tumor microenvironment (TME) responsiveness of nanomaterials, there is tremendous potential for their applications in breast cancer diagnosis and therapy. In the diagnostic arena, nanomaterials serve as core components of novel contrast agents (e.g., gold nanorods, quantum dots, superparamagnetic iron oxide nanoparticles) and biosensing platforms, substantially enhancing the sensitivity and specificity of molecular imaging modalities—such as magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging (FLI)—and enabling high-sensitivity detection of circulating tumor cells and tumor-derived exosomes, among various liquid biopsy biomarkers. In therapy, nanoscale carriers (e.g., liposomes, polymeric micelles) improve tumor targeting and accumulation efficiency through passive and active targeting strategies, thereby augmenting anticancer efficacy while effectively reducing systemic toxicity. Furthermore, nanotechnology has spurred the rapid advancement of emerging modalities, including photothermal therapy (PTT), photodynamic therapy (PDT), and immunotherapy. Notably, the construction of theranostic platforms that integrate diagnostic and therapeutic units within a single nanosystem enables in vivo, real-time visualization of drug delivery, treatment monitoring, and therapeutic response feedback, providing a powerful toolkit for advancing breast cancer toward personalized, precision medicine. Despite challenges that remain before clinical translation—such as biocompatibility, scalable manufacturing, and standardized evaluation—nanomaterials are undoubtedly reshaping the paradigm of breast cancer diagnosis and treatment. Full article

Organ fibrosis is a progressive and often irreversible pathological process characterized by excessive deposition of extracellular matrix, leading to tissue dysfunction and failure. Despite its significant impact on various organ systems, available antifibrotic therapies remain limited. This review focuses on novel therapeutic approaches to inhibit fibrosis and improve clinical outcomes. Current strategies include small molecule inhibitors, monoclonal antibodies targeting fibrosis mediators, gene therapies, and cell-based approaches, including mesenchymal stem cells and induced pluripotent stem cells. In addition, the development of innovative drug delivery systems and combination therapies involving pulsed magnetic fields (PMFs) opens new possibilities for increasing the precision and efficacy of treatment. In recent years, multiomic approaches have enabled a better understanding of fibrosis mechanisms, facilitating the personalization of therapy. The role of artificial intelligence in drug discovery has also increased, as exemplified by models that support the design of small-molecule inhibitors currently undergoing clinical evaluation. This review discusses key signaling pathways involved in fibrosis progression, such as TGF-β, p38 MAPK, and fibroblast activation, as well as novel therapeutic targets. Although clinical trial results indicate promising potential for new therapies, challenges remain in optimizing drug delivery, considering patient heterogeneity, and ensuring long-term safety. The future of fibrosis therapy relies on integrating precision medicine, combination therapies, and molecularly targeted strategies to inhibit or even reverse the fibrosis process. Further intensive interdisciplinary collaboration is required to successfully implement these innovative solutions in clinical practice. Full article

Lipid nanocarriers present an opportunity to improve conventional drug delivery. In addition, the concomitant use of naturally occurring products with conventional medicines is garnering traction in therapeutic and cosmetic applications. Despite these advances, the rational design of lipid nanoparticles, including lipid selection, remains a challenge. We previously validated the use of Hansen solubility parameter (HSP) predictions for selecting synthetic lipids for utilization in lipid nanocarrier manufacture. Herein, we aimed to validate the use of HSP data to predict minoxidil solubility in natural and/or essential oils with known hair growth activity. We employed a dual-tiered screening strategy that integrated HSP predictions and experimental validation. Experimentally, minoxidil showed the highest solubility in shea butter, stearic acid, and rosemary oil. Further, the latter two lipids exhibited the lowest drug-lipid solubility parameter differences (ΔδT = 6.8 and 6.1 MPa^1/2, respectively) and Relative Energy Difference values (1.28 and 1.61, respectively), aligning with the abovementioned laboratory experimental determinations. These findings provide a platform for the streamlined selection of natural oils which can enhance the solubility of minoxidil, in turn having implications for drug loading and/or encapsulation efficiency in formulation of lipidic carriers with potential synergistic hair growth potential. Moreover, this work adds to our understanding of reduced empirical excipient selection for potential decreased associated material costs during formulation development of lipid nanocarriers. Full article