Search Results (18,790)

Background: Fused deposition modeling (FDM) is one of the most well-known and often published methods for 3D-printed drug delivery systems. In early scientific reports, the active pharmaceutical ingredients were added by soaking, but later, a new milestone was established, after researchers started to manufacture their own filaments by hot-melt extrusion (HME). The number of publications covering this method has multiplied in the last decade, a wide range of natural and synthetic polymers have been tested with versatile active pharmaceutical ingredient components, and various printing parameters and their effects have been investigated. Objectives: In this review, we aim to synthesize how the available quality by design approaches and the scientific results established so far can facilitate the creation of a guideline for appropriate quality production of HME-FDM 3D-printed pharmaceuticals. Methods: Based on PRISMA 2020 guidelines, a systematic search of relevant publications from 2015 to 2025 was carried out using the PubMed database. Twenty-six articles were included, based on number of monitored parameters and methodological description. Reporting of important quality processes and material parameters was assessed. Results: HME, the FDM, and analytical testing experiences were compared and collected into three tables from the selected publications. In two different sections, the pharmacopeial dosage-form tests and the involvement of process analytical technologies (PAT) were also analyzed. We found that reporting of influential parameters is heterogenous, and lack of robust reporting schemes limits the development of QbD approaches. Conclusions: Regarding the data, trends were synthetized, and a guideline was created which is limited by inconsistent parameter reporting. Full article

Antibody–drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of action, clinical efficacy, safety profiles, biomarker strategies, and emerging resistance mechanisms. Key safety concerns, including interstitial lung disease (ILD), ocular toxicity, and peripheral neuropathy, are emphasized alongside approaches for re-challenge following toxicity. We further discuss next-generation ADC platforms, including bispecific and conditionally activated constructs, as well as combination strategies with immunotherapy. Collectively, ADCs beyond HER2 are poised to reshape treatment paradigms in NSCLC, offering hope for patients with limited therapeutic options. This review identifies current gaps, highlights ongoing research priorities, and proposes practical considerations for integrating these therapies into clinical practice. Full article

Despite the demand for personalized wound care, integrating diagnostics and therapeutics into a unified platform remains a significant challenge. To address this, we developed a 3D-printed theranostic hydrogel using vat photopolymerization, enabling precise, multifunctional wound management. The hydrogel matrix, composed of poly(acrylamide-co-hydroxyethyl acrylate) and carboxymethyl cellulose, was chemically crosslinked with poly(ethylene glycol) diacrylate. Bromocresol purple was integrated into the photosensitive resin to enhance printing fidelity and serve as a diagnostic indicator, providing a distinct colorimetric shift upon skin infection. For controlled drug delivery, graphene oxide (GO) and levofloxacin were incorporated into the system. The 3D-printed hydrogel demonstrated superior swelling capacity (>600%), ideal for absorbing wound exudate. A semi-quantitative linear colorimetric response was observed across varying pH levels, allowing for clear differentiation between healthy healing skin (pH 4.0–6.0) and infected conditions (pH 7.0 and above). Furthermore, the hydrogel exhibited infection-stimulated therapy, with a cumulative levofloxacin release of 92.63% at pH 8, significantly higher than in acidic conditions. Moreover, the incorporation of GO further optimized the delivery profile by tuning absorption and release rates. Synergizing real-time monitoring and on-demand therapeutic action, this 3D-printed system offers a scalable, robust solution for future-ready, personalized wound management. Full article

Smart hydrogel systems with stimuli-responsive properties are increasingly being investigated in combination with advanced additive manufacturing techniques for targeted drug delivery and wound healing in regenerative medicine; however, their clinical translation remains limited by challenges related to material performance, design complexity, and manufacturing scalability. This review analyzes recent developments in smart hydrogel design and 4D-printed scaffolds, with emphasis on programmable and stimuli-responsive architectures. The literature is selectively evaluated based on relevance to (i) hydrogel structure–property relationships, (ii) 3D/4D printing strategies, and (iii) demonstrated performance in drug delivery and wound healing applications. The analysis highlights design approaches enabling spatiotemporal control of drug release and dynamic scaffold behavior, while also examining how fabrication methods influence functional outcomes. Major limitations are critically assessed, including issues of reproducibility, mechanical stability, long-term performance, and the gap between experimental studies and clinical application. Challenges in defining and implementing 4D printing in biomedical contexts are discussed as well. Overall, this review identifies current design trade-offs, outlines priorities for improving reliability and translational potential, and synthesizes emerging trends in 3D and 4D printed hydrogel scaffolds for precision drug delivery and regenerative wound therapy. Full article

Over the past 200 years (1820–2020), global life expectancy has nearly tripled, increasing from 26 to 72.91 years, due to factors such as poverty reduction and public health initiatives. Today, society faces different challenges than it did centuries ago. In patient care and healthcare system priorities, the goal is to develop smart, feasible, long-lasting, cost-effective, readily available, adverse-reaction-free, adaptable, and personalized solutions that minimize patient discomfort, reduce caregiver effort, and decrease hospitalization duration and costs. In this context, biomaterials serve as versatile tools capable of performing a wide range of diagnostic, therapeutic, and theragnostic functions. Thanks to their biocompatibility, biodegradability, surface chemistry, and responsiveness, biomaterials are currently addressing issues such as patient compliance (through controlled drug-delivery systems and smart wound dressings), long transplant waiting lists, transplant rejection, non-adaptable prosthetics (artificial organs), oncology treatment efficacy (nano-formulations for theragnostics and multiple tumor targeting), and inconsistent in vitro drug-testing models (organs-on-a-chip). In this review, we focus on biomaterials’ smartness, then explore databases for efficient product design, and finally highlight their applications in the biomedical field, especially in drug delivery, tissue engineering, and regenerative medicine. Full article

Dexamethasone induces systemic toxicity, including oxidative stress, inflammation, hematological disturbances, and organ damage, particularly in the lungs and thyroid. Taurine exhibits antioxidant and anti-inflammatory properties, but poor bioavailability limits its efficacy. Nanoparticle delivery may enhance stability and tissue targeting. This study aimed to evaluate the protective effects of taurine-loaded chitosan nanoparticles (Tau–CS NPs) against dexamethasone-induced tissue injury in rats. Forty-eight male Wistar rats were allocated into control, DEXA, DEXA + silymarin, DEXA + taurine, and DEXA + Tau–CS NPs groups. Tau–CS NPs were characterized by TEM, UV–vis, FTIR, encapsulation efficiency, and drug loading. Hematology, oxidative stress markers (CAT, SOD, GSH, MDA), thyroid hormones (T3, T4, TSH, calcitonin), protein profile, lung and thyroid histopathology, and MPO expression were assessed. Tau–CS NPs showed uniform spherical morphology (11–60 nm), high encapsulation (98.2%), and substantial loading (50.36%). Dexamethasone caused hematological, oxidative, thyroidal, and histological disturbances. Tau–CS NPs markedly restored hematological indices, antioxidant defenses, thyroid function, protein profile, and tissue architecture, outperforming free taurine and silymarin. MPO expression was significantly reduced, indicating decreased inflammation. Taurine nanoparticles effectively mitigate dexamethasone-induced systemic and organ-specific toxicity, offering improved bioavailability and targeted delivery, highlighting their therapeutic potential. Full article

This review comprehensively examines magnetic nanomaterials, ferrofluids, and their integration into ferrogel systems, systematically exploring their structural characteristics, dynamic behaviors, preparation techniques, and applications across medical and engineering fields. Structural characterization reveals that particle size and dispersibility directly influence functional efficiency in fluid and gel matrices, such as SAR (specific absorption rate) values in hyperthermia applications. For ferrofluids and magnetic gels, macroscopic behaviors and microscopic mechanisms are governed by key parameters like the magnetic Bond number. Preparation encompasses green synthesis, chemical reagent synthesis, and the cross-linking of these nanoparticles into hydrogel networks. Applications span diverse areas: in medicine, these include targeted hyperthermia, pH-responsive magnetic gel drug delivery, and MRI (magnetic resonance imaging); in engineering, applications range from efficient extraction and triboelectric power generation to magnetically regulated heat transfer and soft gel robotics. The paper also discusses current challenges, including material stability and unclear micro–macro correlations in complex fluid–gel systems, outlining future research directions for multifunctional magnetic materials. Full article

Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based 3D bioprinting. The films incorporated cannabidiol (CBD) and tetrahydrocannabinol (THC) as cyclodextrin inclusion complexes with HPMC or Carbopol as mucoadhesive hydrogel-forming polymers, while terpenes were evaluated as permeation enhancers. Terpenes including 1,8-cineole, d-limonene, α-pinene, and L-menthol were investigated individually and in combinations to assess their ability to enhance buccal cannabinoid permeation. Hydrogel bioinks were prepared and characterized for viscosity, pH, and drug content prior to printing under optimized conditions. The printed films were evaluated for mechanical properties, swelling behaviour, mucoadhesion, in vitro drug release, and ex vivo buccal mucosal penetration. Ex vivo penetration studies demonstrated that combinations of natural terpenes significantly improved CBD penetration compared with individual terpenes and the synthetic enhancer Azone. HPMC-based hydrogel films exhibited superior mechanical strength, cohesive gel matrices, and sustained non-Fickian cannabinoid release, while enhancing transmucosal penetration compared with unformulated drugs. Carbopol-based films showed higher mucoadhesion but weaker mechanical properties and faster erosion-driven release. These findings demonstrate the potential of 3D-printed mucoadhesive hydrogel films as gel-based systems for transmucosal cannabinoid delivery. Full article

The design of multitargeted drug candidates has recently emerged as a highly attractive area of research. Numerous heterometallic compounds have been developed to enhance both the biological efficacy and physicochemical properties of monometallic metallodrugs. Combining classical transition metals with established antitumor activity, such as Pt, Ru, and Au, with other metal-based fragments offers the potential to generate complex compounds with improved pharmacokinetic and pharmacodynamic profiles. Incorporating different bioactive metal cations within a single molecular framework may enhance anticancer activity through metal-specific interactions with distinct biological targets or through improved physicochemical characteristics of the resulting heteronuclear complexes. Recent studies have underscored the significant progress and promising impact of this multitargeted strategy, particularly in systems that combine ruthenium with other biologically active metal centers. This approach may enable selective biological targeting and help overcome drug resistance. This review compiles and analyzes reported ruthenium-based heteronuclear complexes, offering a comprehensive and critical assessment of recent advances in the rational design and synthesis of novel multinuclear compounds as potential chemotherapeutic agents. Particular emphasis is placed on understanding structure–activity relationships, mechanistic pathways, and the role of metal–metal and metal–ligand interactions in modulating biological responses. The findings summarized herein highlight the remarkable efficacy of a wide range of multinuclear ruthenium anticancer complexes and support the hypothesis that synergistic and/or cooperative interactions between distinct metal-based fragments can significantly enhance pharmacological performance, including improved selectivity, stability, and cellular uptake. Furthermore, emerging insights into their modes of action, resistance profiles, and potential for targeted delivery underscore their promise as viable alternatives to conventional therapies. Overall, this dynamic and rapidly evolving field is poised to inspire continued interdisciplinary research and drive the development of next-generation metallodrugs with improved therapeutic indices and clinical potential. Full article

The treatment of skin diseases remains a significant clinical challenge. Cellulose and its derivatives have emerged as research hotspots in skin-related applications due to their excellent biocompatibility, structural modifiability, and biomimetic properties. This review systematically summarizes the diverse construction forms of cellulose-based materials, including films, nanofibrous scaffolds, hydrogels, and aerogels, with a focus on smart responsive systems tailored to various microenvironmental conditions. Their application progresses in acute/chronic wound healing, bacterial infections, burns, scar prevention, immunomodulation, and smart wearable monitoring are highlighted. The underlying mechanisms involving anti-infection, pro-regeneration, microenvironment modulation, and sensing are analyzed, aiming to provide insights for further exploration of cellulose-based materials in skin disease therapy and even smart wearable devices. Full article

Background: Prefilled syringes (PFSs) are increasingly used for self- and assisted administration of high-value parenterals, yet design verification (DV) planning remains challenging due to overlapping drug, device, and combination product expectations, as well as limited harmonization of device components. To the best of our knowledge, there is no publication providing an end-to-end DV approach for developers. This work aims to provide a best-practice template for structuring and justifying DV programs for PFSs, with the explicit intent of improving transparency and offering practical clarity to development teams navigating regulatory and technical complexity. Methods: A risk-based DV approach is presented for an exemplary 1 mL long staked needle glass PFS intended for subcutaneous administration of a surrogate solution representative of a high-concentration biologic. The approach starts with the design inputs which were derived from intended use, user requirements, and the drug’s quality target product profile (QTPP), then translated into design outputs including Essential Drug Delivery Outputs (EDDOs). These outputs were proven by executing drug-independent and simulated drug-dependent DV tests using ISO- and pharmacopeia-aligned methods, including defined sampling, and real-time/accelerated aging. Results: A best-practice DV approach is presented, including test results across the evaluated functional, mechanical, and integrity endpoints. Conclusions: The presented approach provides a transferable DV template linking intended use to acceptance criteria, sample size rationale, and test selection. As a best-practice contribution, it supports more consistent, defensible DV planning for PFSs and may reduce ambiguity in the interface between drug and device development expectations. Full article

Background/Objectives: Curcumin (CUR) is a potent anticancer agent whose clinical application is hindered by its extremely poor aqueous solubility. This study reports the development of enzyme-responsive whey protein isolate (WPI) nanoparticles for CUR targeted delivery. Methods: To overcome the initial solubility barrier, CUR was first formulated as a solid dispersion with WPI using freeze-drying. This process resulted in a significant enhancement in aqueous solubility (up to 1478-fold), with CUR existing in molecular dispersion or in an amorphous state within the protein matrix as confirmed by Differential Scanning Calorimetry (DSC) and Fourier-transform infrared (FT-IR) spectroscopy. The solubilized CUR-WPI solid dispersion was subsequently used to generate nanoparticles via a thermal gelation method, avoiding the use of organic solvents or toxic chemical crosslinkers. Results: The resulting nanoparticles exhibited a high drug loading efficiency of 85%. In vitro release studies demonstrated minimal CUR release in physiological buffer (pH 7.4) over 24 h, whereas exposure to trypsin, a nonspecific serine protease used as an in vitro model for tumor-associated proteolytic activity, triggered rapid nanoparticle degradation and released 95% of CUR within 3 h. Conclusions: These findings suggest that WPI-based nanoparticles developed from solid dispersions offer a promising, biocompatible platform for the solubility enhancement and protease-triggered delivery of hydrophobic anticancer drugs. Full article

Human serum albumin (HSA), as a natural protein carrier, possesses excellent biocompatibility and drug binding capacity. Due to the synergistic effects of the enhanced permeability and retention (EPR) effect and Gp60/SPARC-mediated active targeting, this drug carrier demonstrates favorable tumor selectivity and can be enriched in tumor tissues to achieve long-term therapeutic effects. Particularly, HSA undergoes pH-dependent recycling through the neonatal Fc receptor (FcRn), which significantly prolongs its half-life and enhances its feasibility as a drug delivery platform. In practical clinical applications, the regulation of HSA release rates requires multiple strategies to work synergistically. Additionally, the targeting efficiency of delivery systems due to tumor heterogeneity remains a major bottleneck limiting its universality. This article systematically reviews the unique advantages, clinical applications, challenges, and future perspectives of HSA as a prodrug carrier in tumor therapy. Full article

Rational design of smart nanogels for drug delivery requires molecular-level understanding of how structural evolution and drug–carrier interactions couple under multiple stimuli. Here, pH/temperature dual-responsive P(NIPAM-co-AAc) nanogels containing 0–20 mol% AAc were investigated by combining all-atom molecular dynamics simulations with in vitro ibuprofen (IBU) release experiments under acidic (pH 2.75) and weakly basic (pH 7.4) conditions at 298 and 310 K. The simulations identified CA-5-L-298 as the most retained system, with the lowest IBU diffusion coefficient (0.92 × 10⁻⁷ cm² s⁻¹) and no dissociated molecules under the adopted criterion, whereas CA-15-H-310 showed the highest diffusivity (8.61 × 10⁻⁷ cm² s⁻¹) and dissociated fraction (22%). Consistently, in the urea-free release experiments, CA-15-H-310 exhibited the highest 24 h cumulative release (69.4%), while CA-5-L-298 remained among the low-release systems (35.9%). Pore analysis, hydrogen-bond statistics, MM/PBSA calculations, and urea-competition experiments together support the view that IBU release is influenced by both mesh steric sieving and polymer–drug affinity switching, and correlation analysis provides quantitative support for linking the MD descriptors with the experimental release behavior. Overall, the simulations reproduce the qualitative trends in the experiments and provide a molecular-level framework for rationalizing the observed release behavior in dual-responsive nanogels. Full article

Poly(lactic-co-glycolic acid) (PLGA) is one of the most extensively investigated biodegradable polymers for biomedical applications, owing to its tunable degradation kinetics, established biocompatibility, and regulatory approval. In implantology, PLGA-based systems have emerged as versatile platforms for scaffolds, coatings, and localized drug delivery, aimed at enhancing osseointegration and tissue regeneration. This review provides a focused and up-to-date analysis of PLGA applications in dental and orthopedic implantology, with particular emphasis on advances reported over the past decade. Unlike previous reviews that predominantly address general drug delivery or broad tissue engineering applications, this work establishes a direct correlation between polymer composition (LA:GA ratio), processing strategies, and biological outcomes, including degradation behavior, mechanical performance, and host response. Special attention is given to multifunctional PLGA systems incorporating antibiotics, growth factors, and bioactive nanoparticles, highlighting their role in improving antibacterial efficacy and osteogenesis. Emerging technologies such as nanostructured composites, additive manufacturing, and stimuli-responsive delivery platforms are critically evaluated. Key limitations—including acidic degradation by-products, burst release kinetics, and translational barriers—are discussed in the context of clinical applicability. By integrating physicochemical design with biological performance and recent clinical trends (2024–2025), this review proposes a framework for the rational development of next-generation PLGA-based implant systems. Full article