Search Results (425)

Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study aimed to develop a sustained-release ocular insert containing bromfenac sodium (BS)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) with an initial 3% (w/w) free BS fraction incorporated into a poly(vinyl alcohol) (PVA) matrix designed to achieve a dual-phase release profile for improved postoperative therapy. Methods: PLGA-based MPs were fabricated using a double emulsion solvent evaporation technique and incorporated into PVA films to produce ocular inserts with varying MP content. Formulations were characterized for morphology, particle size, zeta potential, drug loading, entrapment efficiency, mucoadhesion, drug distribution, and in vitro release. Data were analyzed by an ANOVA and t-tests with p < 0.05 as significance. Results: MPs were smooth, spherical, and well-dispersed in the PVA inserts. Particle sizes ranged from 3.7 to 5.6 µm, with drug loading 7–8% and entrapment efficiencies 47–52%. Multiphoton imaging confirmed uniform drug distribution. In vitro release showed a dual-phase profile with an initial burst followed by sustained release for up to 4 days, with only negligible further release through Day 6 in one formulation (M1-7525). Conclusions: The developed BS-loaded PLGA MP/PVA insert demonstrated a dual-phase release profile relevant to postoperative ocular inflammation. Its biodegradable, single-application design holds promise for enhancing compliance and therapeutic outcomes in ophthalmic care. Full article

Drug-coated balloons (DCBs) have transformed percutaneous coronary intervention (PCI) by delivering antiproliferative drugs directly to the arterial wall, offering a stent-less approach that mitigates the risks associated with permanent metallic implants. Initially developed for in-stent restenosis (ISR), DCBs have demonstrated robust efficacy in reducing neointimal hyperplasia and target lesion revascularization (TLR) rates across diverse coronary lesions, including small vessel disease (SVD), de novo lesions, and complex anatomies such as bifurcation lesions. Paclitaxel-coated balloons have long been the cornerstone of DCB therapy due to their established clinical outcomes, but sirolimus-coated balloons are emerging as a promising alternative with potentially superior safety profiles and sustained drug release. The pharmacological mechanism of DCBs relies on rapid drug transfer during brief balloon inflation, achieving high local concentrations without residual foreign material. Landmark trials, such as BASKET-SMALL 2, RESTORE SVD, and AGENT IDE, have demonstrated comparable or non-inferior outcomes of DCBs versus drug-eluting stents (DESs) in specific settings, with lower rates of stent thrombosis and shorter dual antiplatelet therapy (DAPT) requirements. Despite these advances, challenges persist, including optimizing drug formulations, ensuring uniform delivery, and addressing calcified lesions. Ongoing research into novel coatings, dual–drug systems, and artificial intelligence (AI)-guided interventions is poised to redefine PCI strategies. This review provides a comprehensive analysis of drug-coated balloon (DCB) angioplasty, not limited to specific clinical scenarios such as in-stent restenosis, small vessel disease, or bifurcation lesions, highlighting their transformative role in coronary artery disease (CAD) management. Instead, it addresses the full spectrum of pharmacological principles, mechanisms of action, clinical indications, comparative efficacy across various coronary artery disease contexts, and future directions of DCBs. Full article

Numerous studies on specific cannabis compounds (cannabinoids and phenolic acids) have demonstrated their therapeutic potential, with their administration methods remaining a key research focus. Transdermal drug delivery (TDD) systems are gaining attention due to their advantages, such as painless administration, controlled release, direct absorption into the bloodstream, and its ability to bypass hepatic metabolism. The thin films obtained via pulsed laser deposition consist of micro- and nanoparticles capable of migrating through skin pores upon contact. This study investigates the interaction of phenolic compounds in hemp seeds with pulsed laser beams. The main goal is to achieve the ablation and deposition of these compounds as thin films suitable for TDD applications. The other key objective is optimizing laser energy to enhance the industrial feasibility of this method. Thin layers were deposited on glass and hemp fabric using dual pulsed laser (DPL) ablation on a compressed hemp seed target held in a stainless steel ring. The target was irradiated for 30 min with two synchronized pulsed laser beams, each with parameters of 30 mJ, 532 nm, pulse width of 10 ns, and a repetition rate of 10 Hz. Each beam had an angle of incidence with the target surface of 45°, and the angle between the two beams was also 45°. To improve laser absorption, two approaches were used: (1) HS-DPL/glass and HS-DPL/hemp fabric, in which a portion of the stainless steel ring was included in the irradiated area, and (2) HST-DPL/glass and HST-DPL/hemp fabric—hemp seeds were mixed with turmeric powder, which is known to improve laser interaction and biocompatibility. The FTIR and Micro-FTIR spectroscopy (ATR) performed on thin films compared to the target material confirmed the presence of hemp-derived phenolic compounds, including tetrahydrocannabinol (THC), cannabidiol (CBD), ferulic acid, and coumaric acid, along with other functional groups such as amides. The ATR spectra have been validated against Gaussian 6 numerical simulations. Scanning electron microscopy (SEM) and substance transfer tests revealed the microgranular structure of thin films. Through the analyzes carried out, the following were highlighted: spherical structures (0.3–2 μm) for HS-DPL/glass, HS-DPL/hemp fabric, HST-DPL/glass, and HST-DPL/hemp fabric; larger spherical structures (8–13 μm) for HS-DPL/glass and HST-DPL/glass; angular, amorphous-like structures (~3.5 μm) for HS-DPL/glass; and crystalline-like structures (0.6–1.3 μm) for HST-DPL/glass. Microparticle transfer from thin films on the hemp fabric to the filter paper at a human body temperature (37 °C) confirmed their suitability for TDD applications, aligning with the “whole plant medicine” or “entourage effect” concept. Granular, composite, thin films were successfully developed, capable of releasing microparticles upon contact with a surface whose temperature is 37 °C, specific to the human body. Each of the microparticles in the thin films obtained with the DPL technique contains phenolic compounds (cannabinoids and phenolic acids) comparable to those in hemp seeds, effectively acting as “microseeds.” The obtained films are viable for TDD applications, while the DPL technique ensures industrial scalability due to its low laser energy requirements. Full article

Carbohydrate-based hydrogels represent a new advancement in the development of multifunctional biomedical systems, thanks to their intrinsic biocompatibility, structural versatility, and capacity for functional modification. This review examines the latest progress made in employing these materials as intelligent theranostic platforms, with a particular focus on their role as biosensors and therapeutic drug delivery devices. Engineered to interact dynamically with the biological environment, carbohydrate hydrogels enable the site-specific release of therapeutic agents while simultaneously supporting the monitoring of key physiological markers. Their dual functionality offers significant advantages in managing complex pathologies such as cancer, metabolic disorders, and chronic inflammation, where personalized treatment and real-time feedback are essential. By exploring their biological application, this review underscores the pivotal role played by carbohydrate hydrogels in advanced therapeutic technologies. Full article

The Maillard reaction (MR), a non-enzymatic interaction between reducing sugars and amino compounds, plays a pivotal role in developing the flavor, color, and aroma of thermally processed foods. Beyond its culinary relevance, the MR gives rise to a structurally diverse array of compounds, including a novel class of fluorescent nanomaterials known as carbon nanodots (CNDs). These Maillard-derived CNDs, although primarily incidental in food systems, exhibit physicochemical characteristics—such as aqueous solubility, biocompatibility, and tunable fluorescence—that are similar to engineered CNDs currently explored in biomedical fields. While CNDs synthesized through hydrothermal or pyrolytic methods are well-documented for drug delivery and imaging applications, no studies to date have demonstrated the use of Maillard-derived CNDs specifically in drug delivery. This review examines the chemistry of the Maillard reaction, the formation mechanisms and characteristics of food-based CNDs, and their potential functional applications in food safety, bioactivity, and future biomedical use. Additionally, it critically evaluates the health implications of Maillard reaction products (MRPs), including both beneficial antioxidants and harmful by-products such as advanced glycation end-products (AGEs). This integrated perspective highlights the dual role of MR in food quality and human health, while identifying key research gaps needed to harness the full potential of food-origin nanomaterials. Full article

Background: Bladder cancer is a common and heterogeneous malignancy of the urinary tract. Traditional chemotherapy using bivalent platinum drugs such as cisplatin(CDDP) is often limited by severe side effects and acquired resistance. To overcome these limitations, we explored a novel Pt(IV) prodrug, DNP, designed to release both cytotoxic cisplatin and the anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor naproxen(NPX). Methods: We evaluated the cytotoxic activity of DNP using both two-dimensional (2D) monolayer and three-dimensional (3D) spheroid models of bladder cancer cells. Transcriptomic analysis via RNA-seq identified apoptosis- and inflammation-related signaling pathways modulated by DNP. RNA-seq-based transcriptomic profiling revealed that DNP regulates signaling pathways associated with apoptosis and inflammation. The anti-inflammatory effects were evaluated using a lipopolysaccharide (LPS)-induced macrophage model, while the in vivo antitumor efficacy was assessed in an orthotopic MB49 bladder cancer model. Results: Compared with CDDP, DNP significantly increased intracellular platinum accumulation and exhibited superior cytotoxicity. It effectively inhibited tumor proliferation, induced apoptosis, and attenuated inflammation both in vitro and in vivo. Conclusions: These findings suggest that DNP exerts dual antitumor effects through enhanced delivery of cytotoxic and anti-inflammatory agents, offering a promising strategy for bladder cancer therapy. Full article

Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article

Infection control and bleeding management in deep wounds remain urgent and unmet clinical challenges that demand innovative, multifunctional, and sustainable solutions. Unlike previously reported sodium alginate and silk fibroin-based gel formulations, the present work introduces a dual-functional system combining antimicrobial and haemostatic activity in the form of conformable aerogel beads. This dual-functional formulation is designed to absorb exudate, promote clotting, and provide localized antimicrobial action, all essential for accelerating wound repair in high-risk scenarios within a single biocompatible system. Aerogel beads were obtained by supercritical drying of a silk fibroin–sodium alginate blend, resulting in highly porous, spherical structures measuring 3–4 mm in diameter. The formulations demonstrated efficient ciprofloxacin encapsulation (42.75–49.05%) and sustained drug release for up to 12 h. Fluid absorption reached up to four times their weight in simulated wound fluid and was accompanied by significantly enhanced blood clotting, outperforming a commercial haemostatic dressing. These findings highlight the potential of silk-based aerogel beads as a multifunctional wound healing platform that combines localized antimicrobial delivery, efficient fluid and exudate management, biodegradability, and superior haemostatic performance in a single formulation. This work also shows for the first time how the prilling encapsulation technique with supercritical drying is able to successfully produce silk fibroin and sodium alginate composite aerogel beads. Full article

Inflammatory arthritis (IA) is a chronic condition marked by joint dysfunction and pain, posing significant challenges for effective drug delivery. This study separated Perilla frutescens leaf-derived exosome-like nanovesicles (PFE) to effectively penetrate the stratum corneum barrier. These nanovesicles and indomethacin (IND) were subsequently developed into a nanogel designed for topical drug delivery systems (PFE-IND-GEL). PFE exhibited a typical vesicular structure with a mean diameter of 98.4 ± 1.3 nm. The hydrodynamic size and zeta potential of PFE-IND-GEL were 129.6 ± 5.9 nm and −17.4 ± 1.9 mV, respectively. Mechanistic investigations in HaCaT keratinocytes showed that PFE significantly downregulated tight junction proteins (ZO-1 and Occludin, p < 0.01) via modulation of the IL-17 signaling pathway, as evidenced by transcriptomic analysis. In a sodium urea crystal-induced rat IA model, the topical application of PFE-IND-GEL significantly reduced joint swelling (p < 0.05) and serum levels of inflammatory cytokines (IL-6, IL-1α, TNF-α) compared to control groups. Histopathological analysis confirmed the marked attenuation of synovial inflammation and cartilage preservation in treated animals. These findings underscore the dual role of PFE as both a topical permeation enhancer and an anti-inflammatory agent, presenting a promising strategy for managing IA. Full article

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article

Background/Objectives: Leishmaniasis remains a neglected tropical disease, with nearly one million new cases annually and limited investment in research. Current treatments, primarily based on pentavalent antimonials, are associated with severe side effects and increasing resistance. This study aims to develop a novel therapeutic strategy using a nanomaterial functionalized with sialic acid (SA) and colchicine (COL) to selectively target Leishmania braziliensis parasites. Methods: A nanostructured system was engineered by functionalizing its surface with SA and COL. SA was chosen to mimic host cell surfaces, enhancing parasite attraction, while COL was selected for its known leishmanicidal properties. The nanomaterial was designed to concentrate extracellular parasites on its surface via SA-mediated interactions, thereby increasing local COL efficacy. Results: The functionalized nanomaterial demonstrated a dual mechanism: SA facilitated the selective accumulation of Leishmania braziliensis parasites on the nanostructure surface, while COL exerted a cytotoxic effect. This synergistic interaction resulted in enhanced parasite mortality in vitro, suggesting improved selectivity and potency compared to conventional treatments. Conclusions: The proposed nanomaterial offers a promising alternative for leishmaniasis treatment by combining targeted parasite attraction with localized drug delivery. This strategy may reduce systemic toxicity and improve therapeutic outcomes. Full article

Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained in solid tumors due to the immunosuppressive tumor microenvironment (TME). Reactive oxygen species (ROS), which exhibit dual regulatory roles in the TME by regulating immunogenic cell death (ICD) and reprogramming immune cell functionality, have emerged as a pivotal therapeutic target. Nano-enabled drug delivery systems present distinct advantages for TME modulation due to their structural versatility, tumor-specific targeting precision, and spatiotemporally controlled drug release. In particular, ROS-responsive nanoplatforms demonstrate multifaceted immunomodulatory potential by synergistically restoring ICD and remodeling immunosuppressive immune cell phenotypes within the TME. These platforms further amplify the therapeutic outcomes of conventional modalities including chemotherapy, radiotherapy, and photodynamic therapy (PDT) through ROS-mediated sensitization mechanisms. This review comprehensively examines recent breakthroughs in ROS-responsive nanosystems for antitumor immunotherapy, emphasizing their mechanistic interplay with TME components and clinical translation potential. Herein, we provide a framework for developing integrated therapeutic strategies to overcome the current limitations in cancer immunotherapy. Full article

Dual-drug delivery systems using hydrogel–nanoparticle composites have emerged as a versatile platform for achieving controlled, targeted, and efficient delivery of two distinct therapeutic agents. This approach combines the high loading capacity and tunable release properties of hydrogels with the enhanced stability and targeting ability of nanoparticles, providing synergistic benefits in various biomedical applications. While significant progress has been made, previous research has primarily focused on single-drug systems or simple co-delivery strategies, often lacking precise spatial and temporal control. This gap underscores the need for more sophisticated composite designs that enable programmable, multi-phase release. This review discusses representative fabrication methods, including physical embedding, covalent integration, and layer-by-layer assembly, to offer insights into practical implementation strategies. Also we present recent studies focusing on key applications—including wound healing, cancer therapy, infection prevention, transplant immunosuppression, and tissue regeneration—with an emphasis on composite design and formulation strategies, types of hydrogels and nanoparticles, and mechanisms of dual-drug release and evaluation. Recent advances in nanoparticle engineering and hydrogel formulation have enabled precise control over drug release and improved therapeutic outcomes. Dual-drug delivery systems using hydrogel–nanoparticle composites present a promising approach for overcoming the limitations of conventional monotherapy and achieving synergistic therapeutic effects. Ongoing research continues to optimize the design, efficacy, and safety of these systems, paving the way for their clinical translation. Full article

Background/Objectives: This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through a metronomic schedule using a transporter-targeted nanoemulsion (NE), with the goal of improving antitumor efficacy and immune modulation. Methods: AT and DT were co-encapsulated in a NE system (AT/DT-NE#E) incorporating deoxycholic acid–DOTAP (D-TAP), biotin-conjugated phospholipid (Biotin-PE), and d-α-tocopherol polyethylene glycol succinate (TPGS) to exploit bile acid and multivitamin transport pathways and inhibit P-glycoprotein efflux. The optimized NE was characterized physicochemically and evaluated for permeability in artificial membranes and Caco-2/HT29-MTX-E12 monolayers. Pharmacokinetics, tumor suppression, and immune cell infiltration were assessed in vivo using rat and CT26.CL25 mouse models. Results: AT/DT-NE#E showed enhanced permeability of AT and DT by 45.7- and 43.1-fold, respectively, across intestinal cell models and improved oral bioavailability by 118% and 376% compared to free drugs. In vivo, oral metronomic AT/DT-NE#E reduced tumor volume by 65.2%, outperforming intravenous AT/DT. Combination with anti-PD1 therapy achieved a 942% increase in tumor suppression over the control, accompanied by marked increases in tumor-infiltrating CD45⁺, CD4⁺CD3⁺, and CD8⁺CD3⁺ T cells. Conclusions: Oral metronomic administration of AT/DT via a dual-transporter-targeted NE significantly improves drug absorption, tumor inhibition, and immune response. This strategy presents a safe and effective approach for colon cancer therapy, particularly when combined with immunotherapy. Full article