Search Results (10,176)

Background: Conventional transdermal drug delivery systems are often limited by poor skin permeability and low drug loading efficiency, necessitating the development of advanced delivery platforms. Objectives: This study aimed to develop and optimize photopolymerizable bioinks (PBs) for liquid crystal display (LCD)-based 3D printing of crosslinked hydrogel microneedles (cHMNs) to enhance transdermal delivery of estradiol valerate (E2V). Methods: A Box–Behnken design (BBD) was used to optimize the effects of Gantrez™ S-97, Jurymer™, and polyvinyl alcohol (PVA) on viscosity, exposure time, hardness, and elasticity, with strong predictive performance (R² = 0.9702–0.9907). Results: Estradiol valerate-loaded nanoparticles (E2V-NPs) were prepared via ionotropic gelation, exhibiting a particle size of 698.33 (0.78) nm, PDI of 0.50 (0.06), zeta potential of −39.09 (7.32) mV, and high encapsulation efficiency (86.87 (0.78)%). The optimized PBs enabled fabrication of uniform cHMNs (~800 µm height) with adequate mechanical strength (hardness 20.45 (1.23) N; elasticity 2.97 (0.49) MPa) and effective insertion capability. The E2V-NPs-loaded cHMNs exhibited sustained drug release over 12 days (~56.92 (4.27)%). Skin permeation studies showed a significantly enhanced flux (10.81 (4.55) µg/cm²/h) and cumulative permeation (12.94 (2.06) µg/cm²) compared to topical E2V-NPs and suspension, along with increased skin accumulation (38.55 (0.10) µg). Cytotoxicity studies confirmed that E2V and E2V-NPs were biocompatible (>80% viability), while PBs showed concentration-dependent cytotoxicity. Conclusions: Overall, this integrated platform combining design of experiment, nanoparticles, microneedles, and LCD 3D printing offered a promising strategy for enhancing transdermal drug delivery efficiency and reproducibility. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a complex etiology and a protracted disease course. Active ingredients from traditional Chinese medicine (TCM), by leveraging the holistic regulatory advantages of anti-inflammatory activity, immune barrier preservation, and gut microbiota regulation, have shown unique therapeutic potential in the intervention of UC. Although bottlenecks such as unclear targets, fragmented mechanisms of action, and poor druggability constrain the clinical translation of TCM active ingredients, current research efforts are dedicated to overcoming these obstacles. This article reviews the latest research progress (2021–2026) on TCM active ingredients for UC treatment. It analyzes the anti-UC mechanisms from three core dimensions: chemical diversity and pharmacodynamic characteristics, validation of direct targets, and indirect regulation through the “gut microbiota–metabolite” axis. Moreover, it emphasizes recent breakthroughs in druggability optimization technologies, including carrier-based nano drug delivery systems (NDDS), carrier-free NDDS, co-delivery NDDS, and prodrug design strategy. Research demonstrates that TCM active ingredients achieve therapeutic effects by modulating inflammatory signaling networks, restoring intestinal immune homeostasis, repairing the mucosal barrier, and remodeling the gut microenvironment. Simultaneously, the application of novel delivery strategies effectively resolves issues such as poor solubility, low oral bioavailability, and insufficient colon targeting. Finally, this review suggests that future research on TCM active ingredients for UC therapy should concentrate on systematically clarifying multi-level mechanisms and designing clinically translatable smart drug delivery strategies, aiming to provide a theoretical basis and practical reference for promoting TCM modernization and innovative UC drug development. Full article

Multidrug resistance (MDR) remains a major obstacle in cancer therapy, driving treatment failure and disease progression across diverse malignancies. A key determinant of MDR is the overexpression of ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (P-gp/ABCB1), which actively effluxes structurally diverse chemotherapeutic agents and reduces their intracellular accumulation. Despite extensive investigation, clinically effective strategies to overcome P-gp-mediated resistance remain limited. This review provides a comprehensive analysis of the molecular mechanisms underlying P-gp function, including its structural organization, regulation of expression, and role in cellular drug disposition. We highlight the interplay between P-gp activity, oxidative stress, metabolic reprogramming and the tumor microenvironment, emphasizing the complexity of MDR as a dynamic and adaptive process. Emerging therapeutic approaches targeting P-gp-mediated resistance are also discussed, including natural bioactive compounds, nanotechnology-based drug delivery systems, polymeric carriers and novel anticancer agents designed to evade efflux mechanisms. Integrating mechanistic insights with advanced pharmacological strategies may improve intracellular drug retention and therapeutic efficacy. A deeper understanding of P-gp-driven MDR is essential for the development of effective interventions aimed at overcoming drug resistance and improving clinical outcomes in cancer patients. Full article

Bacterial infections pose a serious threat to human health, and antibiotics remain the first-line therapeutic agents in clinical practice. However, the vast majority of antibiotics lack the ability to penetrate cell membranes, which severely limits the number of clinically available options for treating intracellular bacterial infections. Developing efficient intracellular antibiotic delivery strategies is therefore of considerable clinical significance, both for reducing antibiotic dosage and for expanding the repertoire of drugs applicable to intracellular infections. To address this challenge, we constructed a protein-based delivery platform mediated by a cell-penetrating miniprotein for efficient intracellular antibiotic delivery. In this system, bovine serum albumin (BSA), which possesses broad antibiotic-binding capability, was employed as the drug carrier, while the cell-penetrating miniprotein ZF5.3, which is capable of endosomal escape, served as the transmembrane delivery mediator. ZF5.3 was conjugated to BSA via a bioorthogonal reaction, and ceftriaxone (CRO) was selected as the model antibiotic to construct a nanoscale delivery system. The binding interaction between CRO and BSA was characterized using UV-Vis, HPLC, and molecular docking techniques. The assembly of the ZF5.3–BSA delivery platform was confirmed by UV-Vis absorption spectroscopy and gel electrophoresis. Intracellular delivery efficiency was evaluated by confocal fluorescence imaging and flow cytometry, and the results demonstrated that ZF5.3 conjugation enhanced intracellular protein delivery efficiency by over 5-fold. Fluorescence co-localization analysis revealed that ZF5.3-mediated cargo is mainly distributed in the cytoplasm and does not completely co-localize with lysosomal markers, suggesting its ability to effectively escape from lysosomes. An intracellular infection model using Staphylococcus aureus was established. Colony-forming unit (CFU) counting experiments confirmed that the delivery system significantly enhanced the intracellular antibacterial activity of ceftriaxone. CCK8 cytotoxicity assays confirmed that the system is non-toxic to cells. Full article

Traditional mineral drugs represent an underexploited reservoir of natural antitumor agents; however, their clinical translation has historically been hindered by poor bioavailability, non-specific biodistribution, and dose-limiting toxicity. This review comprehensively examines the pharmacological mechanisms and modern formulation strategies driving the renaissance of mineral-based oncology therapeutics. We highlight how mineral drugs exert potent anticancer effects through interconnected pathways, including regulated cell death (e.g., apoptosis, ferroptosis), cell-cycle arrest, and immunomodulation. Crucially, we evaluate recent advances in drug delivery systems, such as liposomes, polymeric nanoparticles, inorganic frameworks, and stimuli-responsive (e.g., pH, redox, enzyme) release systems that successfully overcome traditional pharmacological barriers. These bioengineering strategies not only improve solubility and tumor targeting but also significantly widen the therapeutic window, as evidenced by enhanced tumor suppression and reduced systemic toxicity in preclinical models. Despite this progress, challenges regarding in vivo chemical transformations and tumor heterogeneity remain. Ultimately, we propose a closed-loop “Composition–Mechanism–Delivery” design paradigm to guide future research, facilitating the translation of ethnopharmacological heritage into precision mineral-based therapeutics. Full article

Background/Objectives: The aim of current study was the significant improvement of both the flowability and the compressibility of mesoporous silica microparticles (MSMs), to enable the formulation a potential drug delivery system. MSMs are of emerging interest in the pharmaceutical industry, due to their numerous advantages and versatile applicability, such as improvement in aqueous solubility and epithelial permeability, thus enhancing the oral bioavailability of drugs. However, the formulation of these types of materials has been a major challenge. This problem originates from poor powder flow characteristics due to particle properties. Methods: A binder-free high-shear wet granulation (HSWG) process was performed to improve the flowability and compressibility of the model material, meanwhile preserving its porosity. The prepared granules were characterized by particle size, size distribution, yield percentage, particle morphology, porosity, powder flowability, crushing strength, and stability. Micro-CT measurements were performed to examine the structure of the granules and to see the internal segmentation resulted by the two-step granulation process. The granules were compressed into tablets to evaluate the compressibility behavior based on the models of Kawakita and Walker. The physical parameters of the compressed tablets, such as breaking hardness, tensile strength, and thickness, were tested. Results: The prepared granules were evaluated successfully according to the mentioned properties and found to be satisfactory compared to the raw materials. The binder-free method appeared to be effective, thus the use of binders may be avoided if the process is designed well and critical process parameters (CPPs) selected carefully. The granules showed good stability over a one-year testing period. The micro-CT test also verified the success of the initial concept of preparing core–shell structured granules, and enabled the determination of macropores. Nevertheless, the results were completed with BET measurements to determine specific surface area of the granules. Conclusions: The effect of the critical process parameters of the granulation process on all the mentioned attributes was investigated and since major differences were observed between the batches, the effect of the selected CPPs were also verified. Full article

Theranostics is a novel approach that integrates diagnostic and therapeutic efficacy on a single platform, holding great promise for precision medicine by enabling real-time monitoring of disease progression and therapeutic response. Despite significant advances, the successful development and delivery of theranostic systems are critically limited by multiple biological barriers present at systemic, tissue, cellular, anatomical, and immunological levels. These barriers restrict bioavailability, target accessibility, and therapeutic efficacy, while often increasing off-target accumulation and adverse effects. This review provides a comprehensive overview of the major biological barriers encountered in theranostic development, including physiological barriers such as plasma protein binding, renal clearance, and hepatic metabolism; anatomical barriers like endothelial linings, the blood–brain barrier (BBB), and the tumor microenvironment; cellular barriers involving membrane permeability, intracellular trafficking, and endo-lysosomal entrapment; and immunological barriers such as immune recognition, inflammatory responses, and complement activation. Special emphasis is placed on the BBB, highlighting its structural complexity, transport mechanisms, and strategies such as molecular Trojan-horse technology, receptor-mediated and adsorptive-mediated transcytosis, and nanocarrier-based approaches to enhance central nervous system delivery. The review further discusses targeted delivery challenges, including receptor heterogeneity and multidrug resistance, and critically evaluates current strategies to overcome these barriers through surface functionalization, stimuli-responsive systems, biomimetic carriers, and controlled-release mechanisms. Finally, recent advances, clinical challenges, and future perspectives—including personalized theranostics, artificial intelligence—assisted design, and next-generation barrier-penetrating systems—are explored. Overall, this review aims to provide a structured understanding of biological barriers in theranostics and highlight innovative approaches to improve their translational potential. Full article

Background: Effective strategies for delivering neuroprotective agents to the brain remain a major challenge due to the poor solubility, rapid metabolism, and low bioavailability of promising molecules, such as 7,8-dihydroxyflavone (7,8-DHF). This small-molecule TrkB receptor agonist exhibits significant antioxidant, neuroprotective properties, and additional effects on metabolic regulation, but its therapeutic potential is limited by unfavorable pharmacokinetic characteristics. Nanotechnology-based delivery systems are increasingly explored to improve drug stability, enhance bioavailability, and facilitate direct nose-to-brain transport following intranasal administration. In this study, lipid nanoparticles encapsulating 7,8-DHF were developed using a fish-oil-based lipid core enriched with ω-3 polyunsaturated fatty acids (DHA and EPA) and naturally derived excipients, including soybean lecithin and ε-polylysine. Methods: The formulation was optimized using a Design of Experiments (DoE) approach based on a 2³ full factorial design, evaluating drug concentration, lecithin concentration, and surfactant type (Pluronic^® F127 or Tween^® 80). The main formulation responses considered were particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. Results: The optimized nanoparticles exhibited nanometric dimensions (<250 nm); spherical morphology, confirmed by TEM; low polydispersity (PDI < 0.3); and adequate encapsulation efficiency. Stability studies in simulated biological fluids indicated good physicochemical stability for up to 48 h, while interaction studies with mucin suggested a good interaction within the mucus environment. ROS scavenging capacity was confirmed through the DPPH chemical assay, and in vitro experiments on olfactory ensheathing cells, selected as a biologically relevant model for their anatomical localization along the olfactory pathway, showed reduced cytotoxicity of the encapsulated drug compared with the free form. Conclusions: Collectively, these results support the potential application of the developed nanoformulation in the intranasal delivery of 7,8-DHF. Full article

Cancer remains one of the leading causes of morbidity and mortality worldwide, with lung, breast, and colorectal cancers among the most prevalent and lethal malignancies. In recent years, extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and promising tools in oncology. EVs are membrane-bound vesicles released by most cell types and carry diverse biomolecules, including nucleic acids, proteins, lipids, and metabolites derived from their parent cells. Their presence in biological fluids makes them attractive candidates for liquid biopsy applications and minimally invasive cancer diagnosis. In addition, EVs have gained considerable attention as therapeutic platforms due to their biocompatibility, stability, and ability to deliver functional cargo to recipient cells. Beyond mammalian EVs, plant-derived extracellular vesicles (PDEVs) are increasingly being investigated as scalable and potentially safe nanocarriers for biomedical applications. This review summarizes current advances in the use of EVs for cancer diagnosis and therapy, with particular emphasis on their role as biomarkers, drug-delivery systems, and emerging therapeutic agents. Furthermore, the review discusses current challenges and future perspectives related to EV isolation, characterization, and clinical translation in oncology. Full article

The increasing prevalence of antimicrobial resistance (AMR) has promoted the development of advanced biomaterials capable of overcoming the limitations of conventional antibiotics. In this context, metal nanoparticle hybrid hydrogels (MNHHs) have emerged as multifunctional platforms that integrate the high water-retention capacity and biocompatibility of hydrogels with the antimicrobial properties of metallic nanoparticles (MNPs). This review critically analyzes recent advances in the design, physicochemical properties, antimicrobial mechanisms, and biomedical applications of these systems. Current evidence demonstrates that MNHHs can achieve antimicrobial efficiencies above 98–99%, with minimum inhibitory concentrations as low as 0.78 µg mL⁻¹ and inhibition zones of up to 25 mm against clinically relevant pathogens. Furthermore, the incorporation of MNPs significantly improves the mechanical properties of hydrogels and enables controlled and sustained metal ion release for periods of up to 14 days. Despite these promising results, important challenges remain regarding cytotoxicity, release control, the lack of experimental standardization, and the limited understanding of long-term biological effects. Overall, MNHHs represent a promising strategy for infection control, regenerative medicine, and controlled drug delivery; however, their clinical translation still requires the development of reproducible, safe, scalable, and highly biocompatible systems. Full article

Usnic acid (UA), a prominent lichen secondary metabolite, exhibits a unique dual therapeutic profile in dermatology, though its clinical translation is limited by systemic hepatotoxicity and poor solubility. This review comprehensively evaluates the topical efficacy, molecular mechanisms, and advanced formulation strategies of UA enantiomers and UA-rich extracts. A literature search across PubMed, Scopus, and Google Scholar identified 36 original publications focusing on anti-melanoma activity, photoprotection, and tissue regeneration. In vitro studies demonstrate that UA induces apoptosis in resistant melanoma cell lines (A375, HTB-140) via extrinsic/intrinsic pathways, with (−)-UA effectively overcoming doxorubicin resistance. Conversely, in non-cancerous models, low concentrations of UA accelerate wound and burn healing by upregulating vascular endothelial growth factor (VEGF), stimulating fibroblast proliferation, and optimizing extracellular matrix remodeling while preventing hypertrophic scarring. To mitigate skin sensitization and systemic risks, advanced drug delivery systems—including liposomes, nanoemulsions, chitosan nanogels, and electrospun scaffolds—have been developed, significantly enhancing skin permeability and localized dermal retention. Ultimately, the development of bio-functionalized smart dressings and targeted nano-formulations represents the most viable path toward unlocking the full clinical potential of UA in modern dermatological and oncological care. Full article

In medicine, nanoparticles are used for various purposes, including theranostics, imaging, diagnostics, drug delivery, tissue regeneration and targeted cancer treatments, and to minimize the harmful side effects associated with conventional therapies. Target-specific biomolecules, such as silica nanoparticles (SiNPs) labeled with metallic radionuclides, are becoming increasingly popular. The choice of radionuclide is based on its nuclear properties. Silica has several advantages for nanoparticle synthesis, including high biocompatibility, the capacity for drug encapsulation due to its porous structure, and the potential for extensive surface functionalization, including radiolabeling for imaging and therapeutic applications. A radionuclide can be attached to a silica nanoparticle either directly or through the use of chelators or polymers. Additionally, the capability to encapsulate therapeutic agents within such systems offers significant potential for the development of targeted therapies. This study aims to provide a comprehensive overview of recent developments in the radiolabeling of silica-based nanoparticles, with a focus on their application in nuclear medicine, particularly in diagnostic imaging and targeted radionuclide therapy. Theranostics employs a range of imaging modalities to guide and monitor therapeutic interventions. Principal techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and Optical Imaging (such as fluorescence and bioluminescence). These imaging methods enable precise visualization of pathological sites, facilitate tracking of therapeutic agent distribution, and permit real-time assessment of treatment efficacy. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis, biological heterogeneity, and persistent challenges in staging and treatment selection. This narrative review summarizes current and emerging applications of AI across lung cancer screening and early detection, imaging-based staging and prognostication, tissue and liquid biopsy-based tumor characterization, treatment planning, surgical and intraoperative guidance, and drug discovery. In imaging, deep learning models have demonstrated high performance in pulmonary nodule detection, risk stratification, and prediction of molecular alterations, while also showing promise in improving screening efficiency and reducing interpretive variability. In pathology and liquid biopsy domains, AI enables prediction of driver mutations, immunotherapy response, and survival outcomes directly from histopathology slides, circulating tumor DNA, and other blood-based biomarkers, facilitating minimally invasive precision oncology approaches. In treatment planning and delivery, AI systems are being developed to support clinical decision-making, surgical planning (through advanced image segmentation and delineation of operative anatomy), and intraoperative navigation through robotic and computer vision-enabled platforms. Despite these advances, significant barriers remain, including limited real-world validation, algorithmic biases, workflow integration issues, and unresolved ethical and legal concerns. Future progress will depend on the development of transparent, clinically validated, and generalizable AI systems that augment rather than replace the expertise of clinical providers and healthcare teams. Active engagement from pulmonologists, oncologists, radiologists, and thoracic surgeons will be essential in guiding safe implementation and ensuring that AI-driven innovations translate into meaningful improvements in patient outcomes. Full article

The combination of chemotherapy and immunotherapy represents a promising approach that leverages their complementary benefits. However, the side effects resulting from off-target effects and the low efficiency of immune activation remain a significant concern. Herein, we developed a zinc-doped calcium phosphate (ZCP) nanocarrier for the delivery of the chemotherapeutic drug doxorubicin (DOX). By further encapsulating whole proteins from 4T1 breast cancer cells, we constructed a novel nanodrug delivery system named ZCPDM. This system enables specific targeting of tumor cells and undergoes intracellular degradation to release DOX, Zn²⁺, and Ca²⁺. As a chemotherapeutic agent, DOX induces apoptosis while significantly elevating intracellular reactive oxygen species (ROS), thereby enhancing cytotoxicity. This leads to DNA damage and the release of chromosomal fragments. These DNA fragments, together with Zn²⁺, activate the cGAS-STING signaling pathway and trigger pyroptosis, which promotes more efficient recognition and clearance of tumor cells by the immune system. Through these dual mechanisms, ZCPDM effectively combines chemotherapy and immunotherapy. The anti-tumor efficacy and underlying mechanisms were validated at the cellular level. Furthermore, studies in tumor-bearing mice demonstrated its robust anti-tumor performance and ability to suppress tumor recurrence, along with good biosafety. This targeted drug delivery system achieves safe and synergistic chemo-immunotherapy through homologous targeting-mediated pyroptosis and activation of the cGAS-STING pathway, offering a novel and promising strategy for cancer treatment. Full article

This research analyzes the wavy, axisymmetric flow of a Ree–Eyring non-Newtonian nanofluid, infused with motile microorganisms, within a porous, tapered cylindrical channel under a transverse magnetic field. This investigation presents a theoretical framework that may inform the improvement of energy efficiency and thermal management in biomedical engineering applications, such as drug delivery systems and microfluidic biosensors. The work provides an extended insight by a contribution to the evaluation of entropy generation, explicitly considering the influence of motile microorganisms, thereby bridging a gap in the existing literature. The comprehensive physical model further incorporates the combined effects of Joule heating, viscous dissipation, nonlinear thermal radiation, and chemical reactions. Methodologically, the governing nonlinear equations of the system were rendered tractable under long-wavelength and low-Reynolds-number assumptions and subsequently solved using the numerical Runge–Kutta–Fehlberg technique. The key conclusion is that, based on the present numerical model, careful selection of magnetic field strength and microorganism motility parameters may reduce irreversible energy losses, potentially improving the net usable work in advanced nanofluid transport systems for biomedical applications, subject to experimental validation. The most significant finding reveals that the magnetic field serves as a dual-purpose control parameter: increasing its strength boosts total entropy generation by 20–30% while simultaneously raising the Bejan number, confirming heat transfer as the dominant irreversibility mechanism in the system. Additionally, nanoparticle concentration diminishes substantially with elevated chemical reaction rates and Schmidt numbers, while microorganism density is highly sensitive to the Péclet number, which causes flow disruptions. Full article