Search Results (17,258)

In this study, semi-interpenetrating polymer network (semi-IPN) hydrogels based on methacrylated dextran and native inulin were designed as biodegradable carriers for the colon-specific delivery of uracil as a model antitumor compound. The hydrogels were synthesized via free-radical polymerization, using diethylene glycol diacrylate (DEGDA) as a crosslinking agent at varying concentrations (5, 7.5, and 10 wt%), and their structural, thermal, and biological properties were systematically evaluated. Fourier transform infrared spectroscopy (FTIR) confirmed successful crosslinking and physical incorporation of uracil through hydrogen bonding. Concurrently, differential scanning calorimetry (DSC) revealed an increase in glass transition temperature (T_g) with increasing crosslinking density (149, 153, and 156 °C, respectively). Swelling studies demonstrated relaxation-controlled, first-order swelling kinetics under physiological conditions (pH 7.4, 37 °C) and high gel fraction values (84.75, 91.34, and 94.90%, respectively), indicating stable network formation. SEM analysis revealed that the hydrogel morphology strongly depended on crosslinking density and drug incorporation, with increasing crosslinker content leading to a more compact and wrinkled structure. Uracil loading further modified the microstructure, promoting the formation of discrete crystalline domains within the semi-IPN hydrogels, indicative of physical drug entrapment. All formulations exhibited high encapsulation efficiencies (>86%), which increased with increasing crosslinker content, consistent with the observed gel fraction values. Simulated in vitro gastrointestinal digestion showed negligible drug release under gastric conditions and controlled release in the intestinal phase, primarily governed by crosslinking density. Antimicrobial assessment against Escherichia coli and Staphylococcus epidermidis, used as an initial or indirect indicator of cytotoxic potential, revealed no inhibitory activity, suggesting low biological reactivity at the screening level. Overall, the results indicate that DEGDA-crosslinked dextran/inulin semi-interpenetrating (semi-IPN) hydrogels represent promising carriers for colon-targeted antitumor drug delivery. Full article

Thermosensitive nanogels undergo a volume phase transition in response to temperature changes, making them promising candidates for applications, such as water pollutant remediation and drug delivery. In this study, we investigated the thermosensitive volume phase transition of a neutral poly(N-isopropylacrylamide) (PNIPAM) nanogel using coarse-grained dissipative particle dynamics (DPD) simulations conducted using ESPResSo software with varying bead volumes. Langevin dynamics simulations were employed to compare the results. In DPD simulations, water is explicitly treated, whereas in Langevin dynamics, it is treated implicitly, and hydrophobic interactions are represented by an attractive potential between monomer beads. Our results, including the radius of gyration and various radial distribution functions, revealed a clear volume phase transition as the temperature varied, transitioning from an expanded state to a collapsed state. Notably, the volume phase transition observed in Langevin simulations is attributed to the attractive potential between the PNIPAM monomers, whereas in the DPD simulations, it arises from implicit hydrophobic interactions, obviating the need for an additional attractive potential between the monomer beads. This implicit hydrophobic effect originates from the temperature dependence of the Flory–Huggins interaction parameter. Full article

The recent development in polymer science has gone beyond the traditional linear and randomly functionalizable macromolecules to the architected polymer systems, which integrate modular synthesis and dynamic responsiveness. Although the literature related to polymer synthesis and stimuli-responsive materials and applications is widely discussed, it is common to review the aspects independently, restricting a complete picture of how architectural modularity controls adaptive performance. This gap is filled in this review with an integrated framework of relating modular polymer synthesis, stimuli-responsive design, and application-oriented functionality in a single coherent design philosophy. The scientific novelty of this review is that the focus on modular polymers is not only on synthetic constructs, but is a programmable functional scaffold where the structural precision is the direct determinant of responsiveness, multifunctionality, and performance. Controlled polymerization and post-polymerization modification regimes are mentioned to be tools that allow precise positioning of functional modules, and this allows polymers to respond in predictable ways to environmental stimuli like pH, temperature, light, redox conditions, etc. In addition, the review identifies the role of a synergistic combination of various responsive modules in the emergence of behaviours that would not be reached in conventional polymer systems. This review offers a coherent viewpoint on the future of functional polymers of the next generation by bringing together synthetic approaches to nano-responsive behaviour and real-world technologies, such as drug delivery, self-healing surfaces, adaptive surfaces, and biosensing surfaces. The framework in the present paper provides a logical route towards the development of environmentally friendly, multifunctional, and adjustable polymer structures. Full article

Lung cancer in never-smokers (LCINS) represents a distinct clinical entity driven by dominant oncogenic alterations and characterized by a low tumor mutational burden. Although tyrosine kinase inhibitors (TKIs) achieve high initial response rates, their long-term efficacy is limited by suboptimal pharmacokinetics, restricted central nervous system (CNS) penetration, tumor microenvironment barriers, and acquired resistance. In this review, we critically assess the current state of nanotechnology-assisted drug delivery systems for LCINS, with a primary focus on how rationally designed nanocarriers can overcome biological barriers, enable molecular subtype-specific therapeutic strategies, and address mechanisms that limit clinical efficacy and durability of response. We conducted a structured literature search using PubMed and Web of Science (January 2022 to November 2025), focusing on primary studies reporting the preparation, physicochemical properties, and therapeutic performance of nanocarriers in in vitro and in vivo models, as well as available pharmacokinetic and clinical data. LCINS is characterized by inefficient vasculature, high extracellular matrix density, active efflux transporters, and immunosuppressive niches, and is frequently complicated by brain metastases. Nanocarrier-based platforms can enhance aqueous solubility, prolong systemic circulation, and improve tumor or CNS targeting. Co-delivery systems combining TKIs with nucleic acid-based therapeutics, together with stimuli-responsive platforms, offer the potential for simultaneous modulation of multiple oncogenic pathways and partial mitigation of resistance mechanisms. In summary, nanotechnology provides a promising strategy to improve both the efficacy and specificity of targeted therapies in LCINS. Successful clinical translation will depend on biologically aligned carrier–payload combinations, scalable and reproducible manufacturing processes, and biomarker-guided patient selection. Full article

Lower respiratory tract infections caused by Pseudomonas aeruginosa are a global concern. Patients with chronic lung diseases such as cystic fibrosis and non-cystic fibrosis bronchiectasis often do not receive adequate antibiotic delivery through conventional routes. P. aeruginosa employs several mechanisms, including biofilm formation and efflux pumps to limit the accumulation of bactericidal drug concentrations. Direct drug delivery to the lung epithelial lining fluid can increase antibiotic concentration and reduce treatment failure rates. This review discusses current research and developments in inhaled antibiotic formulations for treating P. aeruginosa infections. Recent studies on particle engineering for the dry powder inhalers of antibiotics emphasized three fundamental principles of development: micro, nano, and nano-in-microparticles. Carrier-free microparticles showed potential for high-dose delivery but suffered from poor aerosolization, which could be improved through a drug–drug combination. Amino acids in a co-spray-dried system improved powders’ aerodynamics and reduced moisture sensitivity while incorporating the chitosan/poly(lactic-co-glycolic acid) (PLGA)-modified release of the drug. Nano-in-microsystems, embedding lipid carriers, showed improved antibiofilm activity and controlled release. We also highlight emerging biologics, including antibacterial proteins/peptides, vaccines, bacteriophages, and probiotics. Research on antibiotics and biologics for inhalation suggests excellent safety profiles and encouraging efficacy for some formulations, including antimicrobial peptides and bacteriophage formulations. Further research on novel molecules and synergistic biologic combinations, supported by comprehensive animal lung safety investigations, will be required in future developments. Full article

To construct a high-performance avermectin (Avm) carrier system, this study utilized the advantages of stereocomplex (SC) crystal formation between poly (L-lactic acid) (PLLA) and poly (D-lactic acid) (PDLA) to prepare Avm-loaded stereocomplex polylactic acid (SC-PLA) nanoformulations via the emulsion solvent evaporation method. The results showed the successful formation of SC-PLA after introducing PDLA into the PLLA matrix, and the influence of SC-PLA crystallinity enabled the fabrication of tunable Avm@SC-PLA nanospheres with a regular spherical morphology. Avm@SC-PLA exhibited controlled release characteristics and possessed pH-responsive properties with specific release behaviors under pH 5.5, 7.4, and 8.0 conditions. The Avm@SC-PLA sustained-release nano system had a series of advantages, including controllable particle size, efficient drug loading, excellent sustained-release performance, good UV-shielding ability, high stability, favorable spreadability, and strong affinity for different leaves. In conclusion, the Avm@SC-PLA nanoformulation not only achieves effective loading and stable encapsulation of Avm but also possesses good structural stability and environmental responsiveness. It provides a novel PLA-based carrier strategy for the efficient delivery of Avm and holds potential application value in the pesticide and pharmaceutical fields. Full article

In recent years, remarkable progress in nanomedicine has been achieved, leading to the development of several nanocarriers which aim to enhance the therapeutic efficacy in cancer treatment. Owing to their high versatility and highly tunable physicochemical properties, alumina (Al₂O₃) and silica (SiO₂) substrates represent promising and innovative nanoplatforms that are widely used in biomedical applications, such as drug-delivery, diagnosis, and biosensing in cancer. In particular, such platforms possess multiple advantageous properties, including mechanical stability, high loading capacity, tunable porosity, excellent biocompatibility, and in vitro and in vivo low toxicity. In this review article, we discuss their emerging role as biosensing platforms and drug delivery systems in oncology. As such, we describe how these substrates enable the incorporation of antibodies against various cancer biomarkers [e.g., cancer antigen 15-3 (CA15-3), serum amyloid A1 (SAA1), epithelial cell adhesion molecule (EpCAM), or human epidermal growth factor receptor 2 (HER2)] for the detection of multiple malignancies. Furthermore, we highlight the development of highly promising alumina- and silica-based platforms for drug delivery (e.g., chemotherapeutics, photosensitizers, or gene delivery agents) in cancer. Ultimately, by providing a comprehensive overview alongside a critical analysis, we demonstrate that such nanostructures represent promising platforms for potential clinical translation in cancer medicine, helping to mitigate the limitations of conventional cancer therapies. Full article

In 2025, the U.S. Food and Drug Administration (FDA) approved 44 new drugs, reflecting a slight decrease compared to previous years but maintaining the overall trends in pharmaceutical innovation. Biologics accounted for 25% of approvals, including nine monoclonal antibodies (mAbs), two antibody–drug conjugates (ADCs), and one fusion protein, with cancer remaining the primary therapeutic focus. TIDES, comprising three oligonucleotides and one peptide, continued to consolidate their presence in the market, with the three oligonucleotides featuring N-acetylgalactosamine (GalNAc) for liver-targeted delivery. Small molecules dominate the remainder, with a high prevalence of N-aromatic moieties and fluorine atoms present in most of the molecules. Peptide manufacturing and sustainability concerns, including PFAS usage, remain key challenges. Despite these advances, the high cost of innovative therapies limits access, particularly in low- and middle-income countries. This report provides a structural and chemical analysis of the newly approved drugs, highlighting trends in molecular design, therapeutic areas, and technological innovations shaping modern drug discovery. Full article

Background: Three-dimensional (3D) printing has been established in pharmaceutical sciences for preparing customized dosage forms with intricate release profiles. However, realizing this potential requires complex design strategies and the careful use of various excipients. This study was designed to evaluate the utility of hypromellose acetate succinate (HPMC-AS) as a singular release-modifying excipient for manufacturing oral solid dosage forms via fused deposition modeling (FDM) 3D printing. Methods: The scope of work encompassed comprehensive material characterization, formulation and production of drug-loaded filaments using hot-melt extrusion (HME), subsequent FDM 3D printing of tablet geometries, and in vitro dissolution studies using mebeverine hydrochloride (MebH) as the model drug. Results: Initial HME processing indicated that the HPMC-AS-based filaments were brittle, presenting technical challenges for direct 3D printing. This issue was successfully overcome by incorporating an additional preheating stage into the FDM printing process, which enabled production of the tablets. Dissolution analysis demonstrated that the 3D-printed mebeverine hydrochloride tablets exhibited delayed and sustained-release characteristics. Conclusions: These results confirm the viability of HPMC-AS as a standalone functional excipient in FDM 3D printing to produce tailored, complex drug delivery systems. Full article

Due to its amphiphilicity, the natural fibrous structural protein, silk fibroin (SF), can adsorb at the oil/water interface, form protective viscoelastic layers, and stabilize emulsions. Biocompatible SF-stabilized emulsions can be used in different fields of cosmetics, food, drug delivery, and biomedicine. Depending on the silk processing method, various emulsion types can be obtained, such as film-stabilized emulsions stabilized by SF molecules and Pickering emulsions stabilized by nanostructured SF or SF particles. Nanostructured SF and SF particles, with β-sheet dominated secondary structures, can overcome the drawback of SF molecules with unstable conformation transition during application, and thus endow higher emulsion stability than SF molecules. The emulsions stabilized by SF nanoparticles can endure heat and high ionic strength, while the emulsions stabilized by SF nanofibers show superior stability at high temperature, high salinity, and low pH due to the strong interfacial entangled nanofiber networks. In this review, the recent progress in research on SF-stabilized emulsions is summarized and generalized, including a systematic comparison of the stabilization mechanisms for different SF morphologies, and the influences of the emulsion fabrication technique, component type and proportions, and environmental conditions on the microstructures and properties of SF-stabilized emulsions. Understanding the stabilization mechanism and factors influencing the emulsion stability is of great significance for the design, preparation and application of SF-stabilized emulsions. Full article

Background/Objectives: Despite the clinical success of immune checkpoint blockade (ICB), its efficacy remains limited in immunologically “cold” tumors, primarily due to poor immunogenicity and an immunosuppressive tumor microenvironment (TME). Chemo-immunotherapy offers a potential strategy to enhance ICB response, yet its application is often hindered by inadequate tumor-targeted delivery and systemic immunosuppressive side effects. Biomimetic nanotechnology represents a promising approach to overcoming these limitations by improving drug delivery and facilitating effective combination regimens. Methods: We developed a biomimetic nanosystem (NVs@DOX) through genetic engineering of cellular membranes and optimized nanoformulation techniques, enabling co-delivery of doxorubicin (DOX) and ICB agents. This design aims to maximize synergistic antitumor effects while minimizing adverse impacts. Results: In vitro studies demonstrated the potent cytotoxicity of NVs@DOX, including significant inhibition of cancer cell proliferation and complete suppression of colony formation. In a 4T1 murine breast cancer model, NVs@DOX treatment led to substantial tumor growth inhibition (approximately 72%) without notable body weight loss, underscoring a favorable safety profile alongside enhanced therapeutic efficacy. Conclusions: The NVs@DOX platform effectively integrates doxorubicin with ICB within a biomimetic nanocarrier, significantly improving chemo-immunotherapy outcomes. This strategy highlights the potential of genetically engineered cellular nanoparticles as a promising combinatorial approach for the treatment of breast cancer. Full article

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic alternatives. In recent years, marine ecosystems have garnered increasing attention as a promising source of bioactive compounds with unique structural and pharmacological properties. Marine-derived toxins and venoms, including tetrodotoxin, ω-conotoxins, anthopleurins, palytoxin, brevetoxin, aplysiatoxin, and asterosaponins, exert cardioprotective effects through diverse mechanisms such as modulation of ion channels, inhibition of sympathetic overactivity, antioxidative actions, and enhancement of myocardial contractility. These properties make them potential candidates for addressing various CVD manifestations, including arrhythmia, hypertension, ischemia–reperfusion injury, and heart failure. However, despite their therapeutic promise, the clinical application of these marine compounds remains limited due to poor tissue selectivity, narrow therapeutic indices, proinflammatory activity, and limited metabolic stability. Structural modifications, advanced drug delivery platforms, and in vivo validation studies are crucial for overcoming these challenges. This review highlights the pharmacological actions, molecular targets, and cardiovascular relevance of selected marine toxins and venoms while also addressing key translational barriers. Advances in biotechnology and peptide engineering are enabling the safer and more targeted use of these compounds. Collectively, marine-derived toxins and venoms represent a largely untapped but highly promising frontier in cardiovascular drug discovery. Strategic research focused on elucidating mechanisms, optimizing delivery, and translating clinical applications will be critical to unlocking their full therapeutic potential. Full article

Cyclodextrins and chitosan are biomaterials largely used as pharmaceutical excipients due to their biocompatibility, biodegradability, and low/absent toxicity, associated with a number of favorable properties. In particular, cyclodextrins complexation is mainly utilized to improve the physicochemical and biological properties of drugs, including solubility, stability, and bioavailability, and to reduce their irritating effect. Nevertheless, some disadvantages related to the fast removal of the complex from blood circulation after in vivo administration, and possible competition effects for interaction with cyclodextrin between the complexed drug and other molecules present in the biological environment, can reduce their efficacy as drug carriers. On the other hand, chitosan is widely employed to take advantage of its mucoadhesive, controlled/targeted release, and permeation-enhancing properties. However, its almost complete insolubility in water and poor affinity towards hydrophobic molecules (as most drugs are) are considered its main drawbacks, which could strongly limit its applicability. Due to the several beneficial properties of both cyclodextrins and chitosan, their joint use could provide additional favorable effects in drug delivery and help overcome their disadvantages, in particular by combining the complexing/solubilizing ability of the former towards hydrophobic molecules with the mucoadhesive and controlled/targeted release properties of the latter. The present review is intended to provide a critical and comprehensive summary of the main relevant investigations performed in the last twenty-five years regarding the applications and possible advantages that can be obtained by the combined use of cyclodextrins and chitosan in the development of more effective drug delivery systems. Full article

Background/Objectives: Alveolar macrophages represent the main path of defense in the peripheral pulmonary tissue, though their role in chronic inflammatory lung diseases shows that their protective function can turn pathological. This study focused on developing a system to passively target the release of the pro-inflammatory cytokine TNF-α through the local delivery of siRNA. Methods: An inhalable aspherical microparticle made up of mesoporous silica nanoparticles, crosslinked by an electrostatic LbL-system embedding the siRNA, was developed. Results: Through testing with the NGI, adequate aerodynamic properties with an MMAD as low as 3.37 µm could be determined, with a GSD as low as 1.46, suggesting a relatively small size distribution even during inhalation. To further understand the interaction of the microrods with the lung parenchyma and the resident cells, the disintegration of the rods in different simulant body fluids, their toxicity, and the cell uptake through dTHP-1 and A549 were observed. This showed slow but continuous disintegration, no toxicity in A549 cells, and high microrod uptake by dTHP-1 cells. To demonstrate the effect of the delivered siRNA on the release of TNF-α, ELISAs were carried out, establishing an inhibitory effect of the siRNA-carrying microcarrier system compared to those without siRNA or loaded with scrambled siRNA. To increase the efficacy of the siRNA, chloroquine as an endosomal escape-enhancing compound was loaded onto the mesoporous silica nanoparticles. This resulted in a significant improvement in siRNA inhibition. Conclusions: The developed formulation is able to reach the targeted structure and inhibit the secretion of TNF-α, with CQ increasing the inhibitory effect of the siRNA. Full article