Search Results (3,286)

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

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

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

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

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

The natural polypeptide drug hirudin, a direct thrombin inhibitor, exhibits potent anticoagulant, anti-myocardial fibrotic, and anti-inflammatory effects in the treatment of cardiovascular diseases (CVD), but its clinical application remains limited by its low bioavailability, insufficient targeting capability, and bleeding risk. In recent years, the development of nanotechnology has enabled peptide drug delivery systems to demonstrate substantial promise in medical practice. Significant progress has been made in overcoming limitations and enhancing therapeutic efficacy against CVD through the use of Hirudin-based drug delivery systems by addressing drug stability in vivo, improving targeting ability, and ultimately achieving responsive release. This paper systematically reviews the mechanisms of action, clinical applications, and novel delivery strategies of the peptide drug hirudin in the treatment of CVD, with a particular focus on recent advances in hirudin-based drug delivery systems, and it also looks forward to future research directions for hirudin delivery systems, including the development of scalable intelligent carriers, the construction of real-time feedback systems, and the establishment of standardized in vitro and in vivo evaluation systems, aiming to present novel strategies for safe and efficient treatment of CVD. Full article

Inflammation is strongly related to the development of multiple chronic diseases, such as cardiovascular and autoimmune diseases, and is considered a crucial target for new therapeutic approaches, since it significantly impacts public health, contributes to high mortality rates, and decreases the quality of life. Conventional anti-inflammatory approaches are commonly used, but they present multiple limitations, such as undesirable side effects and low target-specificity. Medicinal plants and their bioactive phytochemical compounds have been studied in recent years and are considered promising alternatives to classical therapies. They are widely recognized for their capacity to modulate inflammatory pathways, regulate inflammatory responses, and consequently reduce inflammation and related symptoms. Although they are considered a good therapeutic alternative, their application in the human body is limited by certain characteristics, such as low solubility, which leads to rapid metabolism and excretion by the organism, significantly reducing bioavailability; for these reasons, the use of medicinal plants remains a biopharmaceutical challenge. Nanotechnology represents a promising tool in this context, since it can improve several characteristics of these compounds. By incorporating plant-derived compounds in nanosystems, considerable advantages, including sustained release, protection from degradation, an increase in the specificity to target tissues, and consequent reduction in toxicity, can be achieved. Thus, nanosystems promote more favorable therapeutic outcomes. This work aims to compile scientific evidence supporting the use of medicinal plants and their bioactive phytochemical compounds, incorporated in nanosystems, in inflammatory disorders. This review enlarges knowledge by integrating both in vitro and in vivo studies involving multiple medicinal plants and bioactive phytochemical compounds, describing their mechanisms of action and the nanosystems employed for drug delivery. In the future, the need for deeper mechanistic studies, the development of targeted and stimuli-responsive systems, and advancement toward clinically translatable, sustainable, and cost-effective plant-based nanotherapies is required. Full article

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

High-energy methods dominate the development of lipid nanoparticles but often require specialized equipment that increases production costs. Low-energy approaches, particularly those free of organic solvents, offer a promising alternative. This study aimed to obtain nanostructured lipid carriers (NLCs) using a solvent-free, low-energy process combining microemulsification and phase inversion. Cetearyl alcohol and PEG-40 hydrogenated castor oil were selected as the solid lipid and surfactant, respectively; the formulation and process were optimized through a Box–Behnken Design. Incorporation of the ionic surfactant extended colloidal stability, while the poloxamer in the aqueous phase enhanced steric stabilization. Resveratrol was efficiently encapsulated (E.E. = 98%), contributing to reduced particle size (291 nm), improved homogeneity (PDI = 0.25), and positive surface charge (+43 mV). Scale-up yielded stable particles carrying resveratrol with a mean size of 507 nm, PDI = 0.24, and ZP = +52 mV. The optimized formulation remained stable for 90 days at 8 °C. In vitro release demonstrated a sustained and controlled release profile, with significantly lower resveratrol release compared to the free compound. Thermal analysis confirmed drug incorporation within the lipid matrix, while transmission electron microscopy (TEM) revealed spherical particles (~200 nm) and SAXS indicated a nanostructure of ~50 nm. Overall, this study demonstrates that solvent-free, low-energy processing can produce stable and scalable NLC formulations, successfully encapsulating resveratrol with favorable physicochemical properties and controlled release behavior. These findings highlight a simple, cost-effective strategy for developing lipid-based nanocarriers with potential applications in drug delivery. Full article

Background: Solid microneedles (MNs) are effective transdermal delivery devices but are commonly fabricated from metallic or non-biodegradable materials, raising concerns related to sustainability, waste management, and processing constraints. This study aimed to evaluate the suitability of the biodegradable biopolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBHVHHx) as a structuring material for solvent-free fabrication of solid MN arrays and to assess their mechanical performance, insertion capability, and drug delivery potential. Methods: PHBHVHHx MN arrays were fabricated by solvent-free micromolding at 200 °C. The resulting MNs were morphologically characterized by scanning electron microscopy. Mechanical properties were assessed by axial compression testing, and insertion performance was evaluated using a multilayer Parafilm skin simulant model. Diclofenac sodium was used as a model drug and applied via surface coating using a FucoPol-based formulation. In vitro drug release was assessed in phosphate-buffered saline under sink conditions and quantified by UV–Vis spectroscopy. Results: PHBHVHHx MN arrays consisted of sharp, well-defined conical needles (681 ± 45 µm length; 330 µm base diameter) with micro-textured surfaces. The MNs withstood compressive forces up to 0.25 ± 0.03 N/needle and achieved insertion depths of approximately 396 µm in the Parafilm model. Drug-coated MNs retained adequate mechanical integrity and exhibited a rapid release profile, with approximately 73% of diclofenac sodium released within 10 min. Conclusions: The results demonstrate that PHBHVHHx is a suitable biodegradable thermoplastic for the fabrication of solid MN arrays via a solvent-free process. PHBHVHHx MNs combine adequate mechanical performance, reliable insertion capability, and compatibility with coated drug delivery, supporting their potential as sustainable alternatives to conventional solid MN systems. Full article

Folate receptor alpha is expressed at low levels in normal tissues, but is elevated in aggressive breast cancer types and can be utilized for targeted nanoparticle delivery. Hence, we prepared a hybrid nanocarrier based on in-house synthesized mesoporous silica nanoparticles (MSNs) which were further lipid-coated and reinforced with folic acid (FA). Thorough physicochemical evaluation was performed including dynamic light scattering (DLS), powder x-ray diffraction (PXRD), thermogravimetric analysis (TGA), and nitrogen physisorption. In vitro dissolution of the model drug doxorubicin was carried out in release media with pH 7.4 and pH 5.5. The cytotoxic potential and cellular uptake were investigated in MCF-7 breast cancer cells via the MTT assay, doxorubicin fluorescence measurement, and microscopy. The potential amelioration of doxorubicin’s cardiotoxicity was evaluated in vitro on the H9c2 cell line. The results showed MSNs with significant pore volume (1.38 cm³/g) and relatively small sizes (98.05 ± 1.34 nm). The lipid coat and FA attachment improved the physicochemical stability and sustained release pattern over 24 h. MSNs were non-toxic, while when doxorubicin-loaded, they caused moderate cytotoxicity. The highest cytotoxic activity was observed with folate-functionalized, doxorubicin-loaded nanoparticles (NPs). Even though non-loaded folate-functionalized NPs exhibited significant cytotoxicity, their physical mixture with doxorubicin was inferior in MCF-7 cytotoxicity as opposed to the corresponding loaded nanocarrier. Fluorescence-based quantification showed a higher intracellular accumulation of doxorubicin when delivered via NPs. These results demonstrate the potential to use folate-functionalized NPs as carriers for doxorubicin delivery in breast cancer cells. Its cardiotoxicity was significantly reduced in the case of loading onto the folic acid-functionalized lipid-coated MSNs. All these findings provide a promising proof-of-concept, although further experimental validation, particularly regarding targeting selectivity and safety, is required. 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

Background: Combating antimicrobial resistance and developing dressings that match all aspects of wound healing will always be challenging. Methods: In this study, hydrogel membranes composed of sodium alginate (SA), polyvinyl alcohol (PVA), and Pluronic-f-127 (F-127) loaded with colistin (C) were formulated. The formulations were divided into two groups: group 1 (SA-PVA-C) and group 2 (SA-PVA-F127-C). Results: The membranes were characterized using multiple techniques, which confirmed component compatibility, physical cross-linking, an amorphous structure, and suitable surface morphology with acceptable porosity. Mechanical testing showed that both groups were suitable for wound-dressing applications. Differences in drug release across media (water, normal saline, and phosphate) were non-significant (p value > 0.05). Drug-loaded membranes (n = 3) from both groups showed antibacterial activity against multidrug-resistant Gram-negative Pseudomonas aeruginosa (ZOI = 20.33 ± 2.51 mm, 21.66 ± 2.08 mm). Conclusions: Overall, the developed hydrogel membranes (both group 1 and group 2) demonstrated promising in vitro potential as colistin delivery systems for wound infection management. Full article

Background/Objectives: MHY498, a tyrosinase inhibitor, exhibits poor water solubility, which limits its topical delivery. Despite the importance of solubility data in rational formulation design, comprehensive information on its solubility behavior in various solvents and across a range of temperatures remains limited. Thus, this study aimed to systematically evaluate the solubility characteristics of MHY498 and to develop a nanosuspension formulation using an antisolvent precipitation approach to facilitate the development of an optimized topical formulation. Methods: In this study, we measured the solubility of MHY498 in various monosolvents and diethylene glycol monoethyl ether (DEGME) + water solvent mixtures at 293.15–313.15 K using a solid–liquid equilibrium technique. Based on these solubility data, MHY498 nanosuspensions were prepared via antisolvent precipitation guided by a Box–Behnken design matrix. In vitro skin permeability was also assessed using a Franz diffusion cell system to assess the topical delivery potential of the MHY498 nanosuspensions. Results: Among the investigated monosolvents, MHY498 exhibited the highest solubility in dimethylformamide, dimethylacetamide, DEGME, while the lowest solubility was observed in water. The solubility increased with temperature and DEGME content in solvent mixtures, and the experimental data were well described by thermodynamic and semi-empirical models, indicating an endothermic and spontaneous dissolution process. Solvent–solute interaction analysis revealed that hydrogen-bonding and nonspecific polarity interactions played key roles in enhancing MHY498 solubility. All nanosuspensions prepared within the design space exhibited particle sizes below 150 nm, and the optimized formulation achieved an average particle size of 28.1 nm. The optimized nanosuspension demonstrated a 3.3-fold increase in the cumulative permeated amounts compared with the conventional microsuspension. Conclusions: These findings demonstrate that a rational solvent selection strategy based on thermodynamic solubility analysis and antisolvent precipitation enables effective nanosuspension formulation of MHY498. The DEGME–water system was identified as a formulation-relevant solvent environment that supports both adequate drug solubilization and reproducible formation of nanosized particles. The resulting nanosuspension exhibited favorable particle size characteristics and enhanced formulation feasibility for topical applications. Therefore, it was shown that the developed nanosuspension system, established through a solubility-driven systematic approach, represents a promising strategy for improving topical delivery of MHY498. Full article

The combination of gold nanoparticles (AuNPs) with hydrogels has drawn significant interest in the design of smart materials as advanced platforms for biomedical applications. These systems endow light-responsiveness enabled by the AuNPs localized surface plasmon resonance (LSPR) phenomenon. In this study, we propose a nanocomposite hydrogel in which gold nanorods (AuNRs) are included in an agarose–carbomer–hyaluronic acid (AC-HA)-based hydrogel matrix to study the correlation between light irradiation, local temperature increase, and drug release for potential light-assisted drug delivery applications. The gel is obtained through a facile microwave-assisted polycondensation reaction, and its properties are investigated as a function of both the hyaluronic acid molecular weight and ratio. Afterwards, AuNRs are incorporated in the AC-HA formulation, before the sol–gel transition, to impart light-responsiveness and optical properties to the otherwise inert polymeric matrix. Particular attention is given to the evaluation of AuNRs/AC-HA light-induced heat generation and drug delivery performances under near-infrared (NIR) laser irradiation in vitro. Spatiotemporal thermal profiles and high-resolution thermal maps are registered using fiber Bragg grating (FBG) sensor arrays, enabling accurate probing of maximum internal temperature variations within the composite matrix. Lastly, using a high-steric-hindrance protein (BSA) as a drug mimetic, we demonstrate that moderate localized heating under short-time repeated NIR exposure enhances the release from the nanocomposite hydrogel. Full article