Search Results (811)

Peritoneal metastasis (PM) is the most frequent and lethal pattern of dissemination in gastrointestinal malignancies. Despite advances in systemic chemotherapy, outcomes remain poor because the unique biology of PM, characterized by poor vascularization and the peritoneal–plasma barrier (PPB), limits drug penetration and contributes to treatment resistance. To address these challenges, several locoregional treatment strategies have been developed, including cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). However, their widespread adoption is constrained by invasiveness, strict patient selection, and inconsistent survival benefits. Normothermic intraperitoneal and systemic treatment (NIPS) has emerged as a practical and less invasive alternative, particularly in East Asia. Through an implanted intraperitoneal port, NIPS enables repeated drug administration, providing sustained regional exposure while imposing minimal procedural burden. Importantly, it can be readily integrated with systemic chemotherapy, making it suitable for long-term multimodal treatment. Among available agents, paclitaxel (PTX) is particularly well suited for intraperitoneal administration because of its prolonged retention within the peritoneal cavity and limited systemic absorption. These pharmacokinetic properties allow high local drug concentrations with relatively low systemic toxicity. Consequently, PTX-based NIPS represents a biologically rational and clinically feasible treatment strategy for PM. This review summarizes the pharmacological rationale, clinical evidence, and emerging innovations in drug formulation and delivery that may further enhance the efficacy of PTX-based intraperitoneal chemotherapy for this challenging disease. Full article

Background: Artemisia absinthium (A. absinthium) is a perennial plant valued for its antibacterial, antioxidant, and anti-inflammatory properties, exhibiting broader therapeutic potential. Given the need to deliver low doses of A. absinthium extract, mesoporous silica nanoparticles have attracted considerable attention as promising nanocarriers due to their distinctive physical and chemical properties. Methods: Physicochemical characterization of the materials was performed and biological assays were conducted to investigate the ROS, antibacterial and antioxidant activity of A. absinthium extract encapsulated within cerium- and calcium-doped mesoporous silica nanoparticles (MNSiCaCe) against both aerobic and anaerobic bacteria. Results: FTIR, SEM, and BET analysis confirmed successful synthesis of the MNSiCaCe. Phytochemical profiling of Artemisia absinthium extract using HPLC revealed the presence of artemisinin and a rich composition of phenolic and flavonoid constituents, with a total phenolic content of 182 ± 3.6 mg GAE/100 g dry plant material and a total flavonoid content of 42.5 ± 0.6 mg QE/100 g. Quantitative drug loading profiling demonstrated that while plain MNSi nanocarriers achieved a loading capacity of 16.96%, the MNSiCaCe enhanced this threshold to 43.11%. The in vitro controlled-release kinetics exhibited a highly prolonged and slow-release profile of the MNSiCaCe. The materials demonstrated excellent hemocompatibility and high mitochondrial activity with human periodontal ligament cells (hPDLCs). Elevated ROS generation was observed under conditions where antibacterial activity was most pronounced. While the artemisinin-doped nanoparticles showed notable antibacterial effects, the complete Artemisia absinthium-loaded nanoparticles achieved a significantly greater reduction in bacterial viability probably due to the synergistic interaction between artemisinin and the extract’s rich polyphenol profile. Conclusions: These findings highlight MNSiCaCe as a promising and safe nanocarrier system for drug delivery, with strong antibacterial potential, offering valuable applications in antibacterial therapies. Full article

Background/Objectives: Despite available treatment options, glaucoma continues to be a leading cause of irreversible blindness. Current medications have multiple limitations, including rapid drainage, ocular irritation, requirement for multiple daily dosings, and systemic side effects. The current study was designed to engineer and characterize a pregabalin-containing enhanced delivery formulation (PRG-EDF) to directly address these inadequacies. Methods: PRG-EDF eye drops were prepared using ingredients that are either U.S. Food and Drug Administration (FDA)-approved for ophthalmic use or have established safety profiles. The formulation was characterized using multiple evaluations, including pH, zetasizer analyses, viscosity, in vitro drug release, transcorneal permeability, determination of dose concentration and volume, systemic exposure, and potential for tachyphylaxis. Efficacy was evaluated using both Dutch belted rabbits and baboons. Results: PRG-EDF provides extended release for up to 24 h. Ex vivo data reveal that PRG-EDF does not alter the inherent high PRG corneal permeability. An intraocular pressure (IOP) study using DB rabbits demonstrates that 40 µL of PRG-EDF, 0.6%, is the optimum dose of our formulation. Comparison of the efficacy of PRG-EDF with commercial products demonstrated its superiority in overall IOP-lowering efficacy. An extended in vivo assessment demonstrated that the potency of PRG-EDF reached maximum IOP-lowering amplitude after 4 weeks of daily dosing. Moreover, an in vivo bioadhesion assay demonstrated that EDF remained on the ocular surface for up to 24 h. Impressively, PRG-EDF is as effective in baboons as in rabbits. Conclusions: We have successfully engineered a highly promising once-daily glaucoma medication with superior efficacy, as illustrated by higher IOP-lowering ability and prolonged duration of action. Full article

Plant extracts and plant-derived bioactive compounds are considered important natural agents in cancer research due to their antiproliferative, pro-apoptotic, antioxidant, anti-inflammatory, and anti-angiogenic effects. However, the low solubility, limited bioavailability, instability, and challenges in their standardization directly limit their therapeutic use. Therefore, the development of new delivery systems has become necessary. In this context, hydrogels are among the biomaterial platforms gaining attention in cancer treatment. This review provides a comprehensive assessment of the potential of hydrogel systems containing plant extracts and plant-derived bioactive compounds in cancer treatment. The article discusses cancer types, the limitations of current treatments, mechanisms of action of plant-derived bioactive compounds against cancer, stimulus-responsive hydrogel systems, and the design criteria for extract-loaded hydrogels. In addition, hydrogel systems containing plant-derived components and combination approaches that use these components alongside anticancer drugs have been investigated. According to the literature, these compounds may increase anticancer activity through local, prolonged release, reduce the toxicity of chemotherapeutic agents in some cases, and exhibit complementary or synergistic antitumor effects with chemotherapeutic drugs. They also point out the potential of treatment strategies targeting the tumor microenvironment. However, researchers need to conduct more comprehensive studies on extraction standardization, biosafety, release kinetics, in vivo efficacy, and clinical scalability. In conclusion, hydrogel systems containing plant extracts and plant-derived bioactive compounds should be considered not as direct alternatives to cancer treatments but as rational biomaterial platforms that enable controlled release, local application, and combination therapies. Full article

Periprosthetic joint infection (PJI) remains a major clinical challenge after total joint arthroplasty because of its association with prolonged antimicrobial therapy, repeated surgery, implant failure, functional disability, and substantial socioeconomic burden. Current strategies, including systemic antibiotics, debridement with implant retention, staged revision, and antibiotic-loaded cement spacers, remain indispensable but are limited by mature biofilm tolerance, protected microbial reservoirs, insufficient local drug penetration, persistent inflammation, and compromised periprosthetic bone repair. Increasing evidence indicates that PJI is not merely bacterial colonization of an implant surface, but a dynamic prosthetic interface disorder involving biofilm persistence, immune dysregulation, inflammatory osteolysis, and failed osseointegration. This review summarizes recent advances in anti-infective prosthetic interface design, emphasizing the transition from passive antibacterial coatings toward multifunctional immuno-antibacterial osseointegrative systems. The pathogenic basis of PJI is first discussed, including conditioning film formation, bacterial adhesion, biofilm maturation, protected reservoirs, immune evasion, and osteolysis. Current clinical management limitations are then evaluated, followed by emerging biomaterial strategies, including anti-adhesive and contact-killing surfaces, active antimicrobial coatings, mature biofilm disruption, biological antibiofilm therapies, smart infection-responsive delivery systems, and osteoimmunomodulatory interfaces. Particular attention is given to balancing early antibacterial activity with cytocompatibility, immune resolution, angiogenesis, mechanical durability, and long-term osseointegration. Finally, key translational barriers are highlighted, including load-bearing and tribological constraints, insufficiently standardized mature biofilm and animal models, limited clinical evidence for advanced smart materials, manufacturing reproducibility, sterilization compatibility, regulatory complexity, and application-specific clinical readiness. Future anti-PJI interfaces should evolve beyond unidirectional bacterial killing toward stage-specific systems integrating biofilm control, immune restoration, vascularized bone regeneration, and durable mechanical performance. Full article

Oral diseases, encompassing conditions such as periodontitis, head and neck squamous cell carcinoma, pulpitis, and mucosal infections, remain a major global health burden due to their high prevalence and complex, multifactorial pathophysiology. The unique anatomical structure of the oral cavity, together with persistent microbial challenges and dynamic immune responses, imposes substantial limitations on conventional drug delivery strategies. Biomimetic cell membrane-based materials have recently emerged as a promising class of delivery platforms, leveraging natural biological interfaces to confer inherent biocompatibility, immune evasion, prolonged circulation, specific targeting, and biofilm-interactive capabilities. These features position them as a transformative approach for improving therapeutic precision and efficacy in oral disease management. In this review, we provide a systematic and materials-oriented overview of biomimetic cell membrane-based drug delivery systems. Specifically, we discuss: (1) the biological sources, classification, and physicochemical properties of membrane-coated systems, along with their fabrication and engineering strategies; (2) the mechanistic basis of targeting, immune modulation, and nanobiointerface interactions, and their applications across representative oral diseases; and (3) current challenges, including scalable manufacturing, functional controllability, biosafety, and clinical translation. Furthermore, we highlight emerging directions such as stimuli-responsive membrane systems and multifunctional integrated platforms, aiming to provide a conceptual framework for the rational design and clinical advancement of biomimetic drug delivery systems in complex disease settings. Full article

B-cell maturation antigen (BCMA), G protein-coupled receptor class C group 5 member D (GPRC5D)-directed immunotherapies, chimeric antigen receptor T-cell (CAR-T) products, bispecific T-cell engagers (BsAbs), and antibody–drug conjugates (ADCs), have transformed the management of MM. Their adoption is now extending beyond tertiary centers following FDA modifications for CAR-T safety and the rapid uptake of off-the-shelf bispecifics suitable for community delivery. Clinicians outside specialist hubs must therefore be conversant with the full toxicity spectrum, including rare but high-consequence events, both for informed consent and for the work-up of post-therapy complications. In this narrative review, we report on the published literature around toxicities of approved and investigational BCMA- and GPRC5D-directed therapies, drawing on pivotal trial data, real-world cohorts, pharmacovigilance studies, and consensus management recommendations, with emphasis on practical recognition and risk mitigation. This review presents toxicities by a temporal pattern including acute (CRS, ICANS, infection, ocular, mucocutaneous), subacute (cranial nerve palsies, parkinsonism, myelitis, peripheral neuropathies IEC-associated enterocolitis and cardiovascular events), and long-term (prolonged cytopenias, second primary malignancies). We discuss validated risk stratification tools, such as the CAR-HEMATOTOX score, EASIX index, and multidisciplinary geriatric assessment, which predicts severe ICANS, infection, and resource utilization, supporting individualized pre-treatment planning. Safe delivery of immune therapies in community settings requires infrastructure for acute critical care, neurology, ophthalmology, infectious disease and long-term surveillance, but is achievable when paired with validated risk stratification and clear referral pathways. Full article

Background/Objectives: Corneal epithelial defects and ulcers remain a significant clinical challenge, often leading to vision impairment and requiring prolonged treatment. In this context, topical insulin has recently gained attention in ophthalmic research. However, conventional eye drops suffer from short residence time and poor bioavailability. To overcome these limitations, the present study evaluates, for the first time in vitro, multiple commercially available soft contact lenses as sustained insulin delivery platforms, analyzing how protein loading influences the essential physicochemical and optical properties of these materials. Methods: The physicochemical properties of eight different commercially available soft contact lens materials, including light transmittance, wettability, and central thickness, were examined before and after insulin loading via a soaking method. Loading efficiency and in vitro release profiles were assessed over time. Corneal cytotoxicity and permeability were evaluated using a human epithelial cell-based model (HCE-2). Results: Among the eight commercial materials screened, Nesofilcon A, Stenfilcon A, and Delefilcon A were selected due to their superior physicochemical performance after insulin loading. At initial concentrations of 1750 and 875 μg/mL, drug loading efficiency reached maximum values of up to 69.3% and 63.1%, with cumulative release values reaching up to 32.4% and 55.1% after 24 h, respectively. Permeability studies confirmed effective insulin diffusion across the HCE-2 cell layer, while cell viability assays indicated no significant cytotoxicity at the lower loading concentration. Conclusions: Insulin-loaded commercial soft contact lenses represent a promising drug–device combination product for the management of persistent epithelial defects and refractory corneal ulcers. These in vitro findings suggest that this approach may enhance drug performance by prolonging residence time and improving corneal bioavailability, while maintaining essential lens properties. However, further in vivo and clinical studies are required to confirm these potential benefits and establish therapeutic efficacy for the management of persistent epithelial defects. Full article

The global prevalence of autoimmune diseases ranges from 3% to 8%, with women at a significantly higher risk than men. The core mechanisms underlying these diseases include impaired T-cell and B-cell immune tolerance, abnormal cytokine production, and aberrant activation of related signaling pathways. Conventional treatments primarily focus on suppressing immune responses, but their efficacy remains limited and they are often associated with substantial side effects. Nanomedicine leverages nanoscale materials to enable precise diagnosis and targeted therapy. Nanocarriers can penetrate biological barriers, enhance cellular uptake, and prolong circulation time in vivo, demonstrating considerable potential for drug delivery. Common nanoscale drug delivery platforms include nanoparticles, polymeric micelles, liposomes, dendrimers, mesoporous materials, hydrogels, and exosomes. Each carrier type possesses distinct characteristics in terms of drug-loading capacity, stability, responsiveness, and biocompatibility, thereby enabling targeted delivery and controlled release. This review summarizes recent advances in nano-delivery technologies for three representative chronic autoimmune diseases: diabetes mellitus (DM), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Nano-delivery systems can improve therapeutic outcomes by optimizing drug delivery, targeting complications, and modulating the pathological microenvironment. They enhance drug bioavailability, reduce off-target and systemic adverse effects, and provide novel strategies for the precise and efficient treatment of chronic autoimmune diseases. Full article

Background: Polymeric drug-eluting films are promising platforms for local antibacterial delivery, but their release profiles depend strongly on the permeability and morphology of the barrier layer. Here, the previously proposed concept of additively manufactured PLACE (Printed Layered Adjustable Cargo Encapsulation) coatings was extended from "single orifice"-defined release toward porosity-assisted barrier control. Two conventional water-soluble porogens, polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), were compared with poly(2-ethyl-2-oxazoline) (PEOx), a hydrophilic polymer proposed as an alternative to PEG in biomedical formulations, but whose use as a leachable porogen has received little attention. Methods: Each porogen was introduced into the upper PLGA barrier of multilayer PLACE films. The resulting films were characterized for film formation, post-hydration morphology by SEM, release of methylene blue and vancomycin, and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Results/Conclusions: PEG was poorly compatible with PLGA and mainly produced surface-localized defects rather than a barrier with controlled permeability suitable for prolonged delivery. PVP K17 provided sustained release at 10 wt.%, whereas 20 wt.% PVP caused burst-dominated release and stronger morphological disruption. PEOx formed developed porosity at lower loading and produced release regimes ranging from several days to approximately two weeks. Vancomycin-loaded films containing 5 wt.% PEOx enabled near-complete release over two weeks while preserving film integrity and showed pronounced early anti-MRSA activity. These results identify porogen selection as a key formulation step and support PEOx as a useful porogen for early high-output antibacterial PLACE coatings. Full article

Mucoadhesive drug delivery systems have emerged as a promising strategy to enhance the therapeutic efficacy of pharmaceuticals by improving drug residence time, bioavailability, and site-specific targeting. Among various materials investigated, biopolysaccharides have gained significant attention due to their biocompatibility, biodegradability, non-toxicity, and inherent mucoadhesive properties. Natural polymers such as chitosan, alginate, pectin, hyaluronic acid, and cellulose derivatives exhibit strong interactions with mucosal surfaces through hydrogen bonding, electrostatic interactions, and polymer chain entanglement. These properties enable prolonged drug retention at mucosal sites, controlled drug release, and enhanced permeation across biological barriers. Mucoadhesive biopolysaccharides have been explored for diverse routes of administration, including oral, buccal, nasal, ocular, vaginal, and pulmonary delivery. Furthermore, chemical modification and nanostructuring of these polymers have expanded their functionality, enabling targeted delivery of small molecules, proteins, peptides, and nucleic acids. This review highlights the mechanisms of mucoadhesion, key biopolysaccharides used in drug delivery, formulation approaches, and recent advances in their application as versatile platforms for novel therapeutic delivery systems. The continued development of mucoadhesive biopolysaccharide-based carriers holds substantial potential for improving treatment outcomes and patient compliance. Full article

Background: Interest in advanced wound dressings for clinical applications is increasing, with biopolymer-based formulations emerging as an effective strategy for wound management. Objectives: This study aimed to develop and characterize sponge-like biopolymeric matrices for the topical delivery of indomethacin as a model anti-inflammatory drug. Methods: Matrices were prepared by combining collagen and methylcellulose (MC) gels in varying ratios, followed by lyophilization. Physicochemical characterization included FT-IR, SEM, contact angle, and water absorption analysis. Biological evaluation involved enzymatic degradation, while biopharmaceutical and pharmacological assessments included in vitro drug release and in vivo testing in Wistar rats with experimentally induced burns. Results: FT-IR analysis confirmed that collagen’s triple-helical structure was preserved in the presence of MC and indomethacin for the samples with maximum 25% methylcellulose. SEM analysis revealed a microporous network with integrated cellulose fibers, where pore size decreased with higher MC content. Compressive strength measurements demonstrated enhanced mechanical resistance with increasing MC content, indicating improved structural stability of the matrices. Moreover, increased MC content led to higher contact angle values but maintained hydrophilicity, while formulations with up to 25% MC exhibited good absorption capacity and structural integrity. Enzymatic degradation studies confirmed that matrices with at least 75% collagen content maintained their structural integrity over time, favoring prolonged application and sustained drug delivery. In vitro drug release followed a biphasic profile, supporting rapid initial anti-inflammatory action followed by gradual release of the drug. In vivo animal studies demonstrated accelerated wound healing in treated rats for all tested matrices. Conclusions: Overall, the developed indomethacin-loaded biopolymeric matrices showed promising structural, functional, and therapeutic properties for effective wound treatment. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) remains difficult to treat because systemic therapy is constrained by limited selectivity, resistance, and toxicity. This study aimed to engineer selenium–chitosan nanoparticles loaded with sunitinib (SeNPs-Ch-SUN) to enhance hepatic delivery and improve anticancer activity against HCC. Methods: The developed system was characterized for particle size (PS), zeta potential (ZP), loading efficiency (LE%), in vitro release, and storage stability. Their cytotoxicity was evaluated in parental HepG2 and Huh-7 cells, multidrug-resistant HepG2 cells, SUN-resistant Huh-7 cells, and THLE-2 normal hepatocytes. In vivo hepatic distribution after intravenous administration was also assessed in rats. Results: SeNPs-Ch-SUN exhibited a mean PS of 93.62 ± 1.06 nm, positive ZP of +24.47 ± 1.31 mV, and LE of 83.8 ± 2.16%. FTIR supported drug association with the chitosan-stabilized selenium system. Compared with free sunitinib, SeNPs-Ch-SUN exhibited sustained drug release, with 51.17 ± 1.26% released at 24 h, whereas the free drug was almost completely released within 3 h. This controlled-release behavior translated in vivo into prolonged hepatic retention and superior liver exposure after intravenous administration. SeNPs-Ch-SUN significantly increased liver AUC_0–24 to 77.23 ± 10.56 µg/g·h, compared with 36.39 ± 9.66 µg/g·h for free SUN, corresponding to an approximately 2.1-fold increase in hepatic exposure. SeNPs-Ch-SUN enhanced cytotoxicity in parental and resistant HCC models, lowered IC₅₀ values, improved selectivity toward malignant cells, and reduced resistance index (RI) in MDR-HepG2 cells, while maintaining reduced toxicity toward normal hepatocytes relative to the free SUN. Conclusions: SeNPs-Ch-SUN represents a promising liver-directed nanoplatform for sunitinib delivery. Full article

Objectives: this study aimed to develop and optimize an intranasal delivery system for Eplerenone (EPL) by incorporating Eplerenone-loaded liposomes (Elip) into an in situ gel system (Elip-GG). The goal was to prolong the residence time of the drug in the nasal cavity and ensure sustained release. Methods: Elip and unloaded liposomes were prepared using the thin-film hydration method. Key formulation variables such as encapsulation efficiency (EE%), mean particle size (MPS), polydispersity index (PDI), and zeta potential (ZP) were optimized. The Elip was then incorporated into a gellan gum (GG) in situ gel to form Elip-GG. The Elip-GG formulation was evaluated based on parameters such as pH, viscosity, rheological behavior, mechanical properties, and in vitro release. Results: the optimal Elip formulation exhibited an EE of 86.3%, a mean particle size of 86.56 nm, a PDI of 0.29, and a ZP of −29.86 mV. The cumulative drug release from the Elip-GG formulation exceeded 93% after 2.5 h. The Elip-GG formulation significantly increased the sustained release of Eplerenone when administered intranasally, offering a promising alternative to oral and parenteral delivery methods for hydrophilic antihypertensive drugs. Full article

Background: While maternal obesity is a well-established risk factor for labor induction failure, the specific impact of regional fat distribution and its direct influence on prostaglandin dose–response profiles remain under-investigated. Relying solely on generalized anthropometric metrics like Body Mass Index (BMI) may obscure the true physiological variations in tissue bioavailability. Therefore, this study aimed to compare dinoprostone-induced labor outcomes between obese pregnant women and non-obese controls, and to evaluate whether ultrasonographically measured abdominal subcutaneous fat thickness (ASFT) can serve as a more precise, independent predictor of induction success and cumulative prostaglandin dose requirements. Methods: This prospective two-center observational study was conducted with 200 single-term pregnant women, comprising an obese study group (n = 100, BMI ≥ 30 kg/m²) and a symmetrical non-obese control group (n = 100, BMI 18.5–29.9 kg/m²). Maternal ASFT was measured via high-resolution ultrasonography at the infraumbilical midline prior to labor induction. All participants initially received a 10 mg dinoprostone vaginal insert governed by a standardized institutional induction protocol. Primary outcomes included successful labor induction (defined as achieving vaginal delivery within 24 h) and cumulative prostaglandin dose requirements. Secondary analyses involved comparative evaluation stratified by obesity classes (Class 1 vs. Class 2–3) and an exploratory ASFT threshold (<30 mm vs. ≥30 mm). Results: Obese women demonstrated significantly lower successful labor induction rates (defined as vaginal delivery within 24 h) compared to the non-obese control group (59.0% vs. 86.0%, p = 0.001). The cumulative dinoprostone dose required for cervical ripening was significantly higher in the obese cohort than in controls (16.8 ± 4.5 mg vs. 12.4 ± 2.2 mg, p < 0.001). Similarly, induction-to-delivery intervals were significantly prolonged in obese parturients (19.2 ± 6.1 vs. 14.6 ± 4.8 h, p < 0.001). Subgroup analysis within the obese cohort revealed that patients with ASFT ≥ 30 mm required higher prostaglandin doses (18.08 ± 3.40 mg vs. 14.14 ± 3.08 mg, p < 0.001) and exhibited lower vaginal delivery rates (45.7% vs. 70.4%, p = 0.012) than those with ASFT < 30 mm. Multivariate logistic regression analysis encompassing the entire study population (n = 200) confirmed that ASFT remained a strong independent predictor of induction failure (Adjusted OR: 1.14; 95% CI: 1.05–1.24, p = 0.002). Conversely, generalized obesity metrics via BMI did not maintain independent significance in the multivariate model (p = 0.420). Conclusions: Increased maternal ASFT is directly associated with blunted drug responsiveness, higher cumulative dinoprostone requirements, and a lower likelihood of successful labor induction. Compared with generalized metrics such as BMI, ultrasonographic measurement of ASFT provides a more precise and clinically relevant assessment of regional maternal adiposity. These findings suggest that incorporating pre-induction ASFT evaluation into routine obstetric practice could improve risk stratification and help clinicians design individualized, precision-based dosing strategies for obese parturients. Full article