Search Results (681)

Metallogels constitute a rapidly expanding class of hybrid soft materials in which metal ions, metal complexes, or metal-containing nanoparticles play a decisive structural and functional role within a three-dimensional gel network. Their unique combination of supramolecular assembly, metal-ligand coordination, and dynamic network behaviour provides tunable mechanical, optical, electrical, redox, and catalytic properties that are not accessible in conventional hydrogels or organogels. This review systematically summarises current knowledge on metallogels, beginning with a classification based on matrix type, dominant metal interaction and functional output, spanning metallohydrogels, metal-organic gels, metal-phenolic gels, nanoparticle-based gels, polymer-based metallogels and low-molecular-weight metallogels. Key synthesis pathways are discussed, including coordination-chemistry-driven formation, metal-ligand self-assembly, in situ reduction, diffusion-mediated strategies, sol-gel-like polymerisation, enzyme-assisted routes, and bio-derived fabrication. Particular emphasis is placed on structure-function relationships that enable the development of catalytic, conductive, luminescent, antimicrobial, and biomedical metallogels. The examples compiled here highlight the versatility and transformative potential of metallogels in next-generation soft technologies, including sensing, energy conversion, wound healing, drug delivery, and emerging applications such as soft electronics and on-skin catalytic or bioactive patches. By mapping current progress and emerging design principles, this review aims to support the rational engineering of metallogels for advanced technological and biomedical applications Full article

Cutaneous leishmaniasis (CL) is a neglected tropical disease for which current chemotherapeutic options are limited by systemic toxicity (such as hepato-nephrotoxicity, arrhythmia, nausea, vomiting) and difficult administration regimens. Pentamidine (PTM), although effective, exhibits severe dose-limiting adverse effects. Polymeric micelles based on Pluronic^® F127 (F127) offer an attractive strategy to improve PTM delivery by enhancing solubility, reducing cytotoxicity, and enabling controlled release. Here, we developed PTM-loaded F127 polymeric micelles and performed a multidisciplinary evaluation combining physicochemical characterization, in vitro biological assays, and gene expression profiling. Dynamic light scattering, UV–visible absorption, fluorescence spectroscopy, and NMR confirmed micelle formation, PTM–polymer interactions, and temperature-dependent assembly. PTM-loaded micelles exhibited biorelevant nanoscale dimensions and preserved stability under physiological conditions. Biological assays demonstrated that F127 micelles markedly reduced PTM cytotoxicity in RAW264.7 macrophages while maintaining potent antileishmanial activity against Leishmania major promastigotes. RT-qPCR analysis revealed modulation of key pathways involved in redox homeostasis, oxidative stress, calcium regulation, apoptosis-like responses, and drug resistance, suggesting that micellar encapsulation influences both PTM bioavailability and parasite stress responses. Overall, PTM-loaded F127 micelles significantly improved the therapeutic index of PTM in vitro. These findings support the potential of F127 polymeric micelles as a promising nanocarrier platform for safer and more effective CL therapy. Full article

Background: gemcitabine is a cytidine analog and major anticancer drug functioning as an antimetabolite. However, its administration by systemic route is accompanied by “burst” and side effects. To limit this, drugs are encapsulated in matrices; metal–organic frameworks (MOFs) are coordination polymers with strong potential for drug encapsulation and delayed release. Methods: mechano-chemical synthesis of solid-state binary complex lag(CYCU-3)(Gem) is described from aluminum MOF (Al-MOF) CYCU-3 and gemcitabine free base (Gem). Synthesis is conducted by liquid-assisted grinding (LAG) with dimethyl sulfoxide (DMSO) followed by its outgassing. The alternative “dry” synthesis results in dry(CYCU-3)(Gem). Materials were characterized by FTIR spectroscopy and XRD, and delayed Gem release was tested to phosphate buffered saline (PBS) at 37 °C. The in vitro toxicity to pancreatic cancer PANC−1 and healthy cells hTERT−HPNE E6/E7/K−RasG12D was assessed by fluorometric assay. Results: in lag(CYCU-3)(Gem) interactions MOF-drug are via non-covalent bonds at O-H and COO⁻ groups of CYCU-3 as found by FTIR marker peak shifts and crystal structure is retained, while dry(CYCU-3)(Gem) shows significant amorphization and loss of functional groups. The lag(CYCU-3)(Gem) but not dry(CYCU-3)(Gem) shows delayed Gem release for 6000 min. The suppression of PANC−1 cells by lag(CYCU-3)(Gem) is time-dependent and it correlates with delayed Gem release. For the first time, a concept of ternary stoichiometric complex lag(CYCU-3)₁(Gem)₁(CIT)₂ is tested that also contains natural organic compound citronellol (CIT), and its structure, bonding and release of Gem are compared to those of binary complex. Bonding is at the O-H groups of CYCU-3 and this complex shows delayed Gem release. Conclusions: binary and ternary complexes of Gem with CYCU-3 yield delayed release and cytotoxicity. LAG is promising for synthesis of solid-state complexes of gemcitabine for delayed release and time-dependent suppression of cancer cells. Full article

Background/Objective: Osimertinib (OSI) is a third-generation tyrosine kinase inhibitor approved for non-small cell lung cancer (NSCLC) therapy. OSI is administered orally; this route limits the amount of OSI reaching the tumor in the lungs and is associated with serious systemic toxicity. This study aimed to develop a dry powder inhalable formulation to provide tumor-targeted delivery and minimize systemic toxicity. To the best of our knowledge, this is the first study to prepare and evaluate a dry powder inhalation formulation of OSI. Methods: Chitosan-coated PLGA nanoparticles (PLGA-C NPs) encapsulating OSI were prepared using a single emulsion-solvent evaporation technique. PLGA-C NPs were assembled into respirable nanocomposite microparticles (NCMPs) via spray drying with L-leucine as a carrier. PLGA-C NPs were characterized for particle size, zeta-potential, encapsulation efficiency, and in vitro efficacy in A-549 cell line. NCMPs were evaluated for solid-state properties, aerosolization performance, stability and in vitro release. Results: PLGA-C NPs exhibited a particle size of 145.18 ± 3.0 nm, high encapsulation efficiency and a positive zeta potential. In vitro studies demonstrated a 3.6-fold reduction in IC50 compared to free OSI, superior antimigratory effects and enhanced cell cycle arrest. Solid-state characterization of NCMPs demonstrated drug encapsulation in the polymer without chemical interaction. NCMPs exhibited excellent aerosolization (mass median aerodynamic diameter of 1.09 ± 0.23 μm, fine particle fraction of 73.48 ± 8.6%) and sustained drug release (61.76 ± 3.9% at 24 h). Stability studies confirmed the physicochemical stability integrity. Conclusions: These findings suggest that this novel dry powder inhalable OSI formulation may improve therapeutic outcomes while reducing systemic toxicity. Full article

Introduction: Magnetic nanoparticles are widely investigated as multifunctional platforms for drug delivery and theranostic applications, yet their biomedical implementation is hindered by aggregation, limited colloidal stability, and insufficient biocompatibility. Hybrid biopolymer coatings can mitigate these issues while supporting drug incorporation. Aim: This study aimed to develop casein–pullulan-coated Fe₃O₄ nanocomposites loaded with xanthohumol, enhancing stability and enabling controlled release for potential theranostic use. Methods: Fe₃O₄ nanoparticles were synthesized through co-precipitation and incorporated into a casein–pullulan matrix formed via polymer complexation and glutaraldehyde crosslinking. A 3² full factorial design evaluated the influence of casein:pullulan ratio and crosslinker concentration on physicochemical performance. Nanocomposites were characterized for size, zeta potential, morphology, composition, and stability, while drug loading, encapsulation efficiency, and release profiles were determined spectrophotometrically. Molecular docking was performed to examine casein–pullulan interactions. Results: Uncoated Fe₃O₄ nanoparticles aggregated extensively, displaying mean sizes of ~292 nm, zeta potential of +80.95 mV and high polydispersity (PDI above 0.2). Incorporation into the biopolymer matrix improved colloidal stability, yielding particles of ~185 nm with zeta potentials near –35 mV. TEM and SEM confirmed spherical morphology and uniform magnetic core incorporation. The optimal formulation, consisting of a 1:1 casein:pullulan ratio with 1% glutaraldehyde, achieved 5.7% drug loading, 68% encapsulation efficiency, and sustained release of xanthohumol up to 84% over 120 h, fitting Fickian diffusion (Korsmeyer–Peppas R² = 0.9877, n = 0.43). Conclusions: Casein–pullulan hybrid coatings significantly enhance Fe₃O₄ nanoparticle stability and enable controlled release of xanthohumol, presenting a promising platform for future targeted drug delivery and theranostic applications. Full article

Leishmaniasis, a widespread, neglected infectious disease with limited effective treatments and increasing drug resistance, demands innovative therapeutic approaches. In this study, we report the fabrication of pentamidine (PTM)-loaded polycaprolactone (PCL) nanofibers using solution blow spinning (SBS) as a potential topical delivery system for cutaneous leishmaniasis (CL). Homogeneous PCL fiber mats were produced using a simple SBS set-up with a commercial airbrush after optimizing several working parameters. Drug release studies demonstrated sustained PTM release profile over time, which was mechanistically modeled by utilizing the complete nanofiber diameter distribution, obtained from SEM analysis of the blow-spun material. FTIR and XRD analyses were performed to investigate the drug–polymer interactions, revealing molecularly dispersed PTM at low-proportion drug/polymers and partial crystallinity at high loadings. The released PTM exhibited significant leishmanicidal activity against Leishmania major promastigotes. Biological investigations showed that SBS-formulated PTM treatment was consistent with the downregulation of parasite genes involved in cell division and DNA replication (cycA, cyc6, pcna, top2, mcm4) and upregulation of the drug response gene (prp1). The controlled delivery of PTM within SBS-fabricated PCL nanofibers provides an effective therapeutic approach to tackle CL and, through the incorporation of additional drugs, could be extended to address a broader range of cutaneous infections. Full article

Coordination polymers (CPs) are garnering attention in the field of medicine day by day. The goal is to develop a CP with biosafe and environment-friendly characteristics. Herein, we report two such novel 3D coordination polymers of zinc-inosine-5′-monophosphate (Zn-IMP) and bpe/azpy (as linkers) which were engineered as metal–organic frameworks that can be used as drug carriers for hydroxyurea (HU). We employed SCXRD, PXRD, solid-state CD, FTIR and TGA for crystal structure characterizations; the results achieved 3D coordination polymers which contain a P2₁ space group with chiral distorted tetrahedral geometry. Solution phase studies like UV–vis and CD were carried out to understand mechanistic pathways for interaction and chirality, respectively. We have also performed computational studies to evaluate the drug delivery capacity of both 3D CPs. Molecular docking and multi-pH molecular dynamics (MD) quantify that HU binds more strongly with CP−1 (ΔG =−10.87 ± 0.12) as compared to CP−2 (ΔG = −7.59 ± 0.26 kcal·mol⁻¹), at normal and basic pH. MD simulation analysis indicated that a more compact and rigid cavity is observed by CP−1 as compared to CP−2 at physiological pH. Across acidic pH, for CP−1 the ligand RMSD increases markedly and U becomes slightly less negative, which indicated partial loss of contacts, thus releasing drugs in a tumor-like environment more easily. These result showed that CP−1 offers stronger binding, higher structural stability and a more pronounced pH-responsive release profile than CP−2, making CP-1 more promising candidate for targeted HU drug delivery, while CP−2 may serve as a weaker-binding, faster-release complement. Full article

Gel-based depots are increasingly recognized as platforms to extend the intratissue residence of local anesthetics (LAs) while reducing systemic exposure. Hydrogels, organogels, and emerging bigels represent three distinct architectures defined by their continuous phases and drug–matrix interactions. Hydrogels provide hydrated polymer networks with predictable injectability, tunable degradation, and diffusion- or stimulus-responsive release, enabling sustained analgesia in perineural, peri-incisional, intra-articular, and implant-adjacent settings. Organogels, formed by supramolecular assembly of low-molecular-weight gelators in lipids or semi-polar solvents, strongly solubilize lipophilic LA bases and enhance barrier partitioning, making them suitable for dermal, transdermal, and mucosal applications in outpatient or chronic pain care. Bigels integrate aqueous and lipid domains within biphasic matrices, improving rheology, spreadability, and dual-solubilization capacity, although their use in LA delivery remains at the formulation stage, with no validated in vivo pharmacology. This narrative review synthesizes the design principles, release mechanisms, and translational evidence across these platforms, highlighting domain-specific advantages and barriers related to mechanical robustness, sterilization, reproducibility, and regulatory feasibility. We propose a platform-level framework in which depot selection is aligned with LA chemistry, anatomical context, and clinical objectives to guide the development of workflow-compatible next-generation LA depots. Full article

Temperature-responsive hydrogels are sophisticated stimuli-responsive biomaterials that undergo rapid, reversible sol–gel phase transitions in response to subtle thermal stimuli, most notably around physiological temperature. This inherent thermosensitivity enables non-invasive, precise spatiotemporal control of material properties and bioactive payload release, rendering them highly promising for advanced biomedical applications. This review critically surveys recent advances in the design, synthesis, and translational potential of thermo-responsive hydrogels, emphasizing nanoscale and hybrid architectures optimized for superior tunability and biological performance. Foundational systems remain dominated by poly(N-isopropylacrylamide) (PNIPAAm), which exhibits a sharp lower critical solution temperature near 32 °C, alongside Pluronic/Poloxamer triblock copolymers and thermosensitive cellulose derivatives. Contemporary developments increasingly exploit biohybrid and nanocomposite strategies that incorporate natural polymers such as chitosan, gelatin, or hyaluronic acid with synthetic thermo-responsive segments, yielding materials with markedly enhanced mechanical robustness, biocompatibility, and physiologically relevant transition behavior. Cross-linking methodologies—encompassing covalent chemical approaches, dynamic physical interactions, and radiation-induced polymerization are rigorously assessed for their effects on network topology, swelling/deswelling kinetics, pore structure, and degradation characteristics. Prominent applications include on-demand drug and gene delivery, injectable in situ gelling systems, three-dimensional matrices for cell encapsulation and organoid culture, tissue engineering scaffolds, self-healing wound dressings, and responsive biosensing platforms. The integration of multi-stimuli orthogonality, nanotechnology, and artificial intelligence-guided materials discovery is anticipated to deliver fully programmable, patient-specific hydrogels, establishing them as pivotal enabling technologies in precision and regenerative medicine. Full article

Background/Objectives: Advanced drug delivery systems (DDSs) are essential for targeted delivery, controlled release, and reduced systemic toxicity, but their clinical adoption is limited by biological barriers, manufacturing complexities, and cost. The aim of this systematic review is to critically evaluate the quantitative relationships between platform design, overcoming biological barriers, and clinical translation outcomes for DDS developed between 2016 and 2025. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (January 2016–April 2025) in accordance with the PRISMA 2020 guidelines. Included studies focused on experimental or clinical data for nanocarrier platforms (liposomes, lipid nanoparticles, polymer systems, biomimetic carriers, extracellular vesicles). Data on platform characteristics, interactions with barriers, pharmacokinetics, manufacturing, and clinical outcomes were extracted and synthesized in narrative form due to the significant methodological heterogeneity. Results: An analysis of 77 included studies confirms that successful clinical translation depends on matching the physicochemical properties of the carrier (size, surface chemistry, material) to specific biological barriers. Liposomes and lipid nanoparticles (LNPs) remain the most clinically validated platforms, exploiting the EPR effect and liver tropism, respectively. Key engineering solutions include stealth coatings, ligand-mediated targeting, and stimulus-responsive materials to overcome barriers such as mononuclear phagocyte system clearance, the blood–brain barrier, and mucosal barriers. Microfluidic and continuous manufacturing processes enable reproducibility, but scalability, cost, and immunogenicity (e.g., anti-PEG responses) remain key translational challenges. Engineered extracellular vesicles, biomimetic carriers, and 3D/4D-printed systems combined with AI-driven design demonstrate the potential for personalized, adaptive delivery. Conclusions: Cutting-edge DDSs have validated their clinical value, but realizing their full potential requires a holistic, patient-centered design approach integrating barrier-specific engineering, scalable manufacturing, and rigorous safety assessment from the earliest stages of development. Further progress will depend on standardizing methods for new platforms (e.g., extracellular vesicles), implementing digital and AI tools, and ensuring translational feasibility as a fundamental principle. Full article

Biocompatible stimuli-sensitive hydrogels are a versatile and promising class of materials with significant potential for various biomedical applications. These ‘’smart’’ hydrogels can dynamically respond to external environmental stimuli such as pH, temperature, enzymes, or biomolecular interactions, enabling controlled drug release, tissue regeneration, wound healing, and biosensing applications. Hydrogels derived from natural polymers, including chitosan, alginate, collagen, and hyaluronic acid, offer key advantages such as intrinsic biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. Their ability to respond to environmental stimuli—including pH, temperature, redox potential, and enzymatic activity—enables control over drug release and tissue regeneration processes. This review explores the fundamental principles governing the design, properties, and mechanisms of responsiveness of natural stimuli-sensitive hydrogels. It also highlights recent advancements in their biomedical applications, discusses existing challenges, and outlines future research directions aimed at improving their functional performance and therapeutic potential for sustainable healthcare solutions. Full article

Background: Individualized care in veterinary practice optimizes pharmaceutical dose regimens, facilitates disease prevention, and supports animal health by considering the animal’s individual profile. Three-dimensional (3D) printing is a suitable technology for manufacturing both tailored drugs and supplements with enhanced efficacy and reduced adverse reactions. Zinc is used to correct deficiencies, support growth, boost the immune system, and treat specific conditions like zinc-responsive dermatosis in dogs. The purpose of the study was to develop and analyze tailored zinc-loaded filaments for the design of custom-made 3D-printed shapes. Methods: Zinc oxide (ZnO) and artificial beef flavor were incorporated into hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC), respectively, to produce tailored 5% or 10% ZnO-containing filaments for 3D printing. The obtained filaments and 3D-printed forms were characterized using sieve analysis, moisture determination, melting point, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction analysis. Results: The characterization of two placebo and four custom-made 3D-printed ZnO supplements suggested that HPMC is a polymer with poor processability, whereas HPC is suitable for incorporating artificial beef flavor and ZnO. FTIR analysis indicated no interaction between the components. Conclusion: The HPC and 10% flavor mixture can be applied as a matrix for manufacturing 3D-printed forms with ZnO for individualized animal care. Full article

Nucleopeptides (NPs) are unnatural hybrid polymers designed by coupling nucleobases to the side chains of amino acid residues within peptides. In this study, we present the synthesis of an Fmoc-protected nucleobase amino acid (NBA) monomer (Fmoc-1,4-TzlNBA_A) with adenine attached to the side chain of L-homoazidoalanine (Aha) through a 1,4-linked-1,2,3-triazole. The coupling was accomplished by a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of Fmoc-Aha and N9-propargyladenine. Subsequently, a homotrinucleopeptide (HalTzl_AAA) containing three 1,4-TzlNBA_A residues was synthesized, using different solid-phase peptide synthesis (SPPS) approaches, and its ability to recognize U-rich motifs of RNAs involved in the HIV replication cycle was studied using circular dichroism (CD) and fluorescence spectroscopy. CD curves confirmed the binding of HalTzl_AAA to U-rich motifs of the transactivation responsive element (TAR UUU RNA HIV-1) bulge and the anticodon stem–loop domain of human tRNALys3 (ASLLys3) by a decrease in the positive ellipticity band intensity around 265 nm during the complexation. 5′-(FAM(6))-labeled TAR UUU and hASLLys3 were used for fluorescence anisotropy binding studies. Fluorescence data revealed that HalTzl_AAA bound TAR’s UUU bulge with a moderate affinity (K_d ≈ 38 µM), whereas the ASLLys3 UUUU-containing loop sequence was recognized with 2.5 times lower affinity (with K_d ≈ 75 µM). Both the standard SPPS method and its variants, which involved the attachment of adenine to the L-Aha side chain using the click reaction during the synthesis on the resin or after the nucleopeptide cleavage, were characterized by a similar efficiency and yield. The CD and fluorescence results demonstrated that HalTzl_AAA recognized the U-rich sequences of the RNAs with moderate and varied affinities. It is likely that both the hydrogen bonds associated with the complementarity of the interacting sequences and the conformational aspects associated with the high conformational dynamics of U-rich motifs are important in the recognition process. The nucleopeptide represents a new class of RNA binders and may be a promising scaffold for the development of new antiviral drugs. Full article

The removal of water pollutants with high selectivity and efficiency is still a huge challenge owing to the complex composition of contaminated water. The preparation, modification of Pickering emulsion microspheres, and their application in the adsorption and removal of non-steroidal anti-inflammatory drugs (diclofenac) in water were studied. Poly(2-(diethylamino)ethyl methacrylate-divinylbenzene), (P(DEAEMA-DVB)) microspheres were prepared by Pickering emulsion polymerization. The P(DEAEMA-DVB) polymer was modified with glycidyl trimethylammonium chloride (GTAC) and phenyl glycidyl ether (PGE) to prepare the adsorbent poly(quaternized and phenyl-functionalized) (P(QP-DVB)) with a substantial quantity of quaternary ammonium functional groups. The non-steroidal anti-inflammatory drugs in aqueous solution was mainly adsorbed by the anion exchange interaction with quaternary ammonium species. The adsorption kinetics coincided with the pseudo-second-order kinetic model, and the adsorption isotherm conformed to the Langmuir isotherm model. The optimized P(QP-DVB) particles exhibited well-defined spherical morphology and a uniform particle size distribution ranging from 15 to 30 µm. Nitrogen adsorption/desorption characterization revealed a high specific surface area of 674 m² g⁻¹ and a pore size distribution from 2 to 25 nm. In addition, the aforementioned microsphere underwent chemical regeneration and exhibits good reusability, thereby reducing both the economic costs and environmental impacts. Full article

The rapid emergence of drug-resistant bacteria demands alternative antimicrobial strategies that extend beyond conventional drugs. In this study, we present the synthesis, structural characterization, and antibacterial evaluation of two new 2-chloro-5-nitrobenzoic acid (2Cl5NBH) derivatives: a methylethanolammonium salt (compound 1) and a 2D coordination polymer (compound 2). Structural characterization by single-crystal X-ray diffraction, complemented by Hirshfeld surface analysis, revealed the supramolecular architectures and highlighted the key intermolecular interactions, providing essential insights into the potential role of these compounds in modulating their physicochemical and biological behavior. Antibacterial assays demonstrated that compound 1 exhibited a broad inhibitory profile against both Gram-positive and Gram-negative bacteria. In contrast, compound 2 exhibited selective inhibition against methicillin-resistant Staphylococcus aureus (MRSA) comparable to that of gentamicin. Full article