Linking interfacial behavior to thermo-diffusive cisplatin release in biopolymeric nanogels.

Formulation and In vitro Characterization of Rosuvastatin Calcium Loaded Chitosan Nanoparticles for Sustained Drug Release

Boswellic Acid-Integrated Chitosan Hybrid Nanogels for pH-Responsive Sustained Sunitinib Release and Lung Tumor Suppression

Stimuli-responsive chitosan-based nanogels have attracted significant interest for drug delivery; however, many reported systems rely on synthetic crosslinkers and function primarily as passive carriers with limited control over network architecture and molecular transport. Here, we report a boswellic-acid-integrated, pH-responsive hybrid nanogel platform in which boswellic acid serves as a bioactive network modifier and hydrophobic domain-forming component within chitosan matrices. Chitosan-boswellic acid (CS-g-BOS) hydrogel precursors were first formed via formaldehyde-assisted network formation and subsequently converted into CS-g-BOS nanogels via STPP-mediated ionic condensation, yielding a shear-thinning porous hydrogel precursor and pH-responsive nanogels relevant to injectable formulation development. The triterpenoid constituents of BOS contribute to the formation of a heterogeneous network, introducing hydrophobic domains that regulate mesh size and diffusion pathways. Comprehensive physicochemical characterization (1H NMR, FTIR, SEM, AFM, DLS, zeta potential, thermal stability, and rheological analyses) showed that BOS incorporation altered nanogel morphology, swelling behavior, rheological response, and release kinetics. The nanogels exhibited high sunitinib encapsulation efficiency (95.52%) and sustained, pH-dependent drug release over 18 days, with accelerated release under acidic tumor-mimicking conditions. Among the tested kinetic models, the Korsmeyer–Peppas model provided the best fit, suggesting that sunitinib malate (SUN) release is diffusion-dominated and modulated by pH-dependent swelling of the CS-g-BOS network. In vitro studies demonstrated cytotoxic and apoptosis-inducing activity against A549 human lung cancer cells, while hemolysis assays indicated favorable blood compatibility. Mouse xenograft studies showed tumor growth suppression, and the chick CAM assay demonstrated antiangiogenic activity; however, histological alterations in the liver, lungs, and kidneys indicated that systemic safety requires further optimization. Overall, this work presents a bio-derived hybrid-network strategy that integrates nanogel network engineering, transport control, and therapeutic functionality, offering a scalable alternative to conventional chitosan nanogels for tumor-responsive drug delivery applications.

Structural reinforcement of Pluronic F127/chitosan thermoresponsive hydrogels through polydopamine incorporation for controllable drug transport.

Thermoresponsive Pluronic-based hydrogels are promising injectable drug delivery platforms but are often limited by weak mechanical integrity and control over drug transport. In this study, we report a polydopamine (PDA)-reinforced Pluronic F127/chitosan composite hydrogel, PCP-DOX, designed to strengthen network integrity and enable near-infrared (NIR)-responsive release without chemical crosslinkers. We have characterized the composite hydrogel for microstructure, rheology, and release kinetics, with photothermal performance and in vitro therapeutic efficacy evaluated under 808 nm NIR irradiation. We found a progressive network densification observed by electron microscopy together with a threefold increase in elastic modulus from approximately 11 kPa to 29 kPa. PCP-DOX exhibited a DOX entrapment efficiency of 98.24 ± 0.20%, indicating effective drug retention. Cumulative doxorubicin (DOX) release at 72 h decreased from 85.5% to 73.3% in the composite relative to the Pluronic-only system. Korsmeyer-Peppas modeling provided the best fit for the release kinetics, suggesting Fickian diffusion-governed transport, with the diffusion exponent increasing from 0.2975 to 0.4531 in the composite system, indicating enhanced diffusional resistance within the network. NIR irradiation at 1.0 W/cm2 enabled transient photothermal modulation of the composite network, producing stepwise release enhancement across repeated irradiation cycles. In vitro studies confirmed cytocompatibility of the blank hydrogel carrier, and combined NIR and DOX treatment yielded greater cytotoxicity than either modality alone, where the predominant cell death mechanism was determined to be apoptosis. These results establish PDA-mediated non-covalent reinforcement as an effective crosslinker-free strategy for engineering thermoresponsive hydrogels with tunable network mechanics and controllable NIR-responsive drug transport for localized chemo-photothermal therapy.

Designing chitosan-coated niosomes: advanced encapsulation strategies to control drug release, enhance stability, and improve therapeutic efficacy.

Nanocarrier-based drug delivery systems have gained considerable attention for enhancing the therapeutic efficacy of bioactive compounds with poor physicochemical properties. Polyphenols such as quercetin and resveratrol exhibit potent antioxidant, anti-inflammatory, and anticancer activities; however, they suffer from poor bioavailability. To address this limitation, we prepared cholesterol-based niosomes using the Tween 20, Tween 40, and Tween 80 surfactants via thin-film hydration, followed by chitosan coating for enhanced stability. The formulations were characterised using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and FTIR spectroscopy, which together confirmed the formation of spherical, nanoscale vesicles, successful chitosan deposition, and physical (non-covalent) entrapment of both drugs. Encapsulation efficiencies exceeded 70% across all systems. Among the formulations, the Tween 40 formulation consistently produced the smallest, most uniform vesicles and showed the highest cumulative drug release, while the Tween 20 and Tween 80 systems favoured stronger drug retention and more gradual release, suggesting the key role of the surfactant tail in controlling drug release. Encapsulation preserved the bioactivity of the polyphenols. Consequently, the drug-loaded niosomes retained strong radical-scavenging activity and reducing capacity, inhibited both Escherichia coli and Staphylococcus aureus (with stronger activity against Gram-negative E. coli), and markedly suppressed the oxidative stress-induced aggregation of γD-crystallin, a key event in cataract formation. MTT assays confirmed their good biocompatibility. Collectively, these findings establish chitosan-coated, cholesterol-Tween niosomes as versatile, biocompatible carriers that provide sustained release and preserve bioactivity, with promising potential for ocular drug delivery and broader biomedical applications.

Formulation and Physicochemical Characterization of ChitosanCoated Simvastatin Nanoparticles

Simvastatin is an effective antihyperlipidemic agent whose clinical utility is limited by poor aqueous solubility, low gastrointestinal absorption, and extensive first-pass metabolism, resulting in reduced oral bioavailability. This study aimed to formulate and characterize chitosan-coated simvastatin nanoparticles as a strategy to improve its physicochemical performance and controlled release properties. Nanoparticles were prepared using the ionic gelation method involving electrostatic interaction between chitosan and sodium tripolyphosphate. The developed formulation was evaluated by in vitro drug release studies, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The release profile demonstrated a biphasic pattern with an initial burst release during the early phase, followed by sustained drug release reaching approximately 70–75% over 300 minutes, indicating effective controlled-release behavior. SEM analysis showed clear morphological transformation from loosely aggregated crystalline simvastatin particles to denser and more cohesive nanoparticulate structures after chitosan coating, confirming successful encapsulation. FTIR spectra retained the characteristic peaks of both simvastatin and chitosan with only minor shifts in band positions, suggesting structural integrity of the drug and absence of significant chemical incompatibility between formulation components. The combined findings indicate that chitosan coating improved the physicochemical characteristics of simvastatin while providing sustained release potential. Therefore, chitosan-coated simvastatin nanoparticles represent a promising oral nanocarrier system for enhancing simvastatin delivery and therapeutic performance. 

Tuning the Network Structure of Crosslinked Chitosan Nanocarriers for Sustained Release of Divalent Micronutrients

Biopolymer‐based nanocarriers have become promising systems for sustained ion delivery due to the tunability of their polymeric network structure. In this study, crosslinked chitosan‐tripolyphosphate (CS‐TPP) nanocarriers were formulated and optimized using a Box‐Behnken design to test how different formulation parameters affect the properties of the nanoparticles. The improved formulation made nanoparticles that were less than 452 nm in size and had high entrapment efficiencies (>87%). FTIR, XRD, DSC, SEM‐EDX, and DLS all showed that a crosslinked polyelectrolyte network had formed and that divalent metal ions (Fe 2 + , Cu 2 + , Zn 2 + ) had been successfully added. We used swelling analysis and release experiments to look into the connection between network structure and transport behavior. The nanocarriers showed a biphasic release pattern, with an initial burst followed by steady diffusion over eight days. Kinetic modeling with the Korsmeyer–Peppas equation showed that transport was controlled by Fickian diffusion (n < 0.45). The differences in release behavior were due to differences in the strength of the metal‐polymer interaction, which changes the network's compactness and diffusion pathways. These results show that process parameters control the structure and transport properties of the network, which allows for tunable sustained release behavior.