Search Results (283)

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

Antioxidant nanomaterials, particularly mesoporous silica nanoparticles (MSNs) functionalized with polyphenols, offer innovative solutions for protecting oxidation-sensitive components and enhancing bioavailability in pharmaceuticals or extending the shelf life of nutraceutical and food products. This study investigates the influence of MSNs functionalized with caffeic acid (MSN-CAF) on powder flow properties and their tableting performance. Aminated MSNs were synthesized via co-condensation and conjugated with caffeic acid using EDC/NHS chemistry. Antioxidant capacity was evaluated using DPPH^●, ABTS^●+, ORAC, and FRAP assays. Powder blends with varying MSN-CAF concentrations (10–70%) were characterized for flow properties (angle of repose, Hausner ratio, Carr’s index), tablets were produced via direct compression, and critical quality attributes (weight uniformity, hardness, friability, disintegration, nanoparticle release) were assessed. MSN-CAF exhibited reduced antioxidant capacity compared with free caffeic acid due to pore entrapment but retained significant activity. Formulation F1 (10% MSN-CAF) showed excellent flowability (angle of repose: 12°, Hausner ratio: 1.16, Carr’s index: 14%), enabling robust tablet production with rapid disintegration, low friability, and complete nanoparticle release in 10 min. Additionally, the antioxidant nanomaterial demonstrated biocompatibility with the HepG2 cell line. MSN-CAF is a versatile nanoexcipient for direct compression tablets, offering potential as an active packaging agent and delivery system in the nutraceutical and food industries. Full article

Peripheral nerve injuries (PNIs) present a significant clinical challenge due to the inherently limited regenerative capacity of the adult nervous system. Conventional therapeutic strategies, such as nerve autografting and systemic pharmacological interventions, are often limited by donor site morbidity, restricted graft availability, and suboptimal drug bioavailability. In this context, gelatin-based hydrogels have emerged as a promising class of biomaterials due to their excellent biocompatibility, biodegradability, and structural similarity to the native extracellular matrix. These hydrogels could offer a highly tunable platform capable of supporting cellular adhesion, promoting axonal elongation, and enabling localized and sustained release of therapeutic agents. This narrative review synthesizes recent advances in the application of gelatin-based hydrogels for peripheral nerve regeneration, with a particular focus on their use as delivery vehicles for neurotrophic factors, stem cells, and pharmacologically active compounds. Additionally, this review provides a foundation for extending our ongoing preclinical study, evaluating the neuroregenerative effects of alpha-lipoic acid, B-complex vitamins, and a deproteinized hemoderivative in a murine PNI model. Although systemic administration has demonstrated promising neuroprotective effects, limitations related to local drug availability and off-target exposure highlight the need for site-specific delivery strategies. In this regard, gelatin hydrogels might represent an excellent candidate for localized, controlled drug delivery. The review concludes by discussing formulation techniques, manufacturing considerations, biological performance, and key translational and regulatory aspects. Full article

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. Full article

Hydroxypropyl methylcellulose (Hypromellose, HPMC) is a well-known excipient used in the pharmaceutical and nutraceutical fields due to its versatile physicochemical properties. HPMC (derived from cellulose and obtained through etherification) varies in polymerization degree and viscosity, factors that both influence its functional applications. Usually, an increased polymerization degree implies a higher viscosity, depending also on the amount of polymer used. Hypromellose plays a crucial role in solid dosage forms, serving as a binder in the case of controlled-release tablets, a film-forming agent in the case of orodispersible films and mucoadhesive films, and a release modifier due to its presence in different polymerization degrees in the case of extended or modified release tablets. However, its compatibility with other excipients and the active ingredient must be carefully evaluated to prevent formulation challenges via several analytical methods such as differential scanned calorimetry (DSC), Fourier Transformed Infrared spectroscopy (FT-IR), X-Ray Particle Diffraction (XRPD), and Scanning Electron Microscopy (SEM). This review explores the physicochemical characteristics, and diverse applications of HPMC, emphasizing its significance in modern drug delivery systems. Full article

Global crop yield is stagnant due to quick release of N from fertilizers and its lower availability at critical growth stages of crops. Urea impregnation of aluminosilicate minerals, especially zeolites, holds NH₄⁺ and delays its release for later crop stages. limited information is available in the literature about the effect of zeolite-based urea fertilizer on soil nitrogen dynamics. Zeolitic urea formulation was prepared and tested in a field experiment under a wheat–rice cropping system. Sources of N were urea and zeolitic urea formulation. N was reduced up to 50% in the treatments from zeolitic urea. Soil parameters (NH₄-N, NO₃-N, available N and total N) and plant parameters were recorded by following the standard procedures. Zeolitic urea retained the highest contents of NH₄-N and NO₃-N at critical growth stages (booting and maturity) of wheat crop. Zeolitic urea retained the highest NO₃ in 0–30 cm soil depth, while these were highest at 60–90 cm depth with urea. Grain yield of wheat crops with N_100%U were similar to that of with N_75%ZU, where 25% less N was applied and nitrogen use efficiency was improved to 25.82% by zeolitic urea. Zeolite-based N fertilizer retains N in soil for an extended period of time and maintains crop yield even with less applied N as compared with urea. Full article

Springback represents the deflection of a workpiece after releasing the forming tools or dies, which influences the quality and precision of the final products. It is basically governed by the elastic strain recovery of the material after unloading. Most approaches only implement reverse bending to determine the final shape of the formed product. However, stretch plays significant role whe the blank is held by a blank holder. In this paper, an algorithm is presented to calculate the contributions of both stretch loads and bending moments to elastic deformation during springback for each element, and to combine them mathematically and geometrically to achieve the final shape of the product. Comparing the results of this algorithm for different sheet metal forming processes with experimental measurements demonstrates that this technique successfully predicts a wide range of springback with reasonable accuracy. The advantage of this approach is its accuracy, which is not sensitive to hardening and softening mechanisms, the magnitude of plastic deformation during the forming process, or the size of the object. The application of the proposed formulation is limited to long profiles (plane-strain cases). However, it can be extended to more general applications by adding the effect of torsion and developing equations in 3D space. Due to the explicit nature of the calculations, data-processing time would be reduced significantly compared to the sophisticated algorithms used in commercial software. Full article

Cellulose acetate butyrate (CAB) and cellulose acetate propionate (CAP) are biobased materials that are insoluble in water and present a potential alternative to fossil-based plastics. Solvent removal-induced in situ matrices are gaining attention as an innovative dosage form for localized drug delivery for periodontitis therapy. This study aims to develop levofloxacin hemihydrate (Lh)-loaded in situ matrices formed through solvent removal, incorporating various molecular weights (MWs) and concentrations of CAB and CAP. Increased MWs and higher concentrations of these cellulosic esters significantly improved formulation viscosity and injection force, contributing to enhanced phase inversion and greater matrix toughness. Microscopic analysis of interfacial phase changes revealed progressive thickening of the matrix over time, which was influenced by polymer concentration and limited solvent movement. The transformed matrices with high MW CAP and elevated CAB content demonstrated prolonged drug release, predominantly following first-order kinetics, suggesting drug dissolution and diffusion through the scaffold structure. CAB-based in situ matrices containing 15% and 20% polymer exhibited low viscosities suitable for injection, along with optimal gel formation for maintaining their shape, and adhered effectively to periodontal pockets. These matrices provided extended Lh release for up to 120 h and inhibited the growth of periodontopathic bacteria for over 15 days. Therefore, the developed Lh-loaded in situ matrices show promise as an effective treatment for periodontitis, warranting further research to explore their therapeutic potential. Full article

In the context of the circular economy, the valorization of bio-derived waste has become a priority across various production sectors, including food processing and packaging. Gelatin (Gel), a protein which can be recovered from meat industry byproducts, offers a sustainable solution in this regard. In this study, pork-derived gelatin was used to develop novel edible active packaging films, designed for meat products. Glycerol (Gl) was used as a plasticizer. Two types of montmorillonite-based nanohybrids were employed as both reinforcing agents and carriers of antioxidant/antibacterial compounds: eugenol-functionalized montmorillonite (EG@Mt) and citral-functionalized montmorillonite (CT@Mt). The active films were formulated as Gel/Gl/xEG@Mt and Gel/Gl/xCT@Mt, where x = 5, 10, or 15 wt.%. Controlled-release kinetics showed that EG@Mt released up to 95% of its adsorbed eugenol, whereas CT@Mt released up to 55% of its adsorbed citral. The films were evaluated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and tested for antibacterial activity against Escherichia coli and Listeria monocytogenes. Results demonstrated that the Gel/Gl/xEG@Mt films exhibited superior antioxidant and antibacterial performance compared to the Gel/Gl/xCT@Mt films. All formulations were impermeable to oxygen. Although the incorporation of EG and CT slightly reduced cell viability, values remained above 80%, indicating non-toxicity. In conclusion, the film containing 15 wt.% EG@Mt achieved an oxygen transmission rate of zero, an effective concentration (EC₆₀) of 9.9 mg/L to reach 60% antioxidant activity, and reduced E. coli and L. monocytogenes populations by at least 5.8 log CFU/mL (p < 0.05), bringing them below the detection limit. Moreover, it successfully extended the shelf life of fresh minced pork by two days. Full article

Cisplatin, a widely used chemotherapeutic agent, is limited by its poor bioavailability, rapid systemic clearance, and severe side effects. To overcome these limitations, hydroxyapatite–gelatin composite microspheres were developed to improve drug entrapment efficiency (DEE) and provide sustained drug release. Various formulations were prepared by incorporating chitosan either by mixing once or through a sequential coating strategy. By adjusting the loading procedure, the DEE increased from 58% to 99%. The composite microsphere effectively controlled the total drug release duration, extending it from one month to over 5 months. Moreover, the MTT assay demonstrated that all samples effectively inhibited cell growth, with cell viability reduced to less than 20% after 2 weeks of experimentation. These findings demonstrate that the sequential chitosan coating method offers superior drug entrapment and prolonged release compared to mixing chitosan once, exhibiting its potential as a sustained drug delivery system for cancer treatment. Full article

Microplastics (MPs), particularly fibrous MPs, have emerged as a significant environmental concern due to their pervasive presence in aquatic and terrestrial ecosystems. The textile industry is a significant contributor to MP pollution, particularly through the production of synthetic fibers and natural/synthetic blends, which release substantial amounts of fibrous MPs. Among the various types of MPs, fibrous MPs account for approximately 49–70% of the total MP load found in wastewater globally, primarily originating from textile manufacturing processes and the domestic laundering of synthetic fabrics. MP shedding poses a significant challenge for environmental management, requiring a comprehensive examination of the mechanisms and strategies for the mitigation involved. To address the existing knowledge gaps regarding MP shedding during the textile production processes, this brief review examines the current state of MP shedding during textile production, covering both dry and wet processes, and identifies the sources and pathways of MPs from industrial wastewater treatment plants to the environment. It further provides a critical evaluation of the existing recycling and upcycling technologies applicable to MPs, highlighting their current limitations and exploring their potential for future applications. Additionally, it explores the potential for integrating sustainable practices and developing regulatory frameworks to facilitate the transition towards a circular economy within the textile industry. Given the expanding application of textiles across various sectors, including medical, agricultural, and environmental fields, the scope of microplastic pollution extends beyond conventional uses, necessitating urgent attention to the impact of fibrous MP release from both synthetic and bio-based textiles. This brief review consolidates the current knowledge and outlines the critical research gaps to support stakeholders, policymakers, and researchers in formulating effective, science-based strategies for reducing textile-derived microplastic pollution and advancing environmental sustainability. Full article

The effectiveness and uses of chitosan nanoparticles (CNPs) in drug delivery systems are examined in this work. Important results include the improved drug encapsulating efficiency: CNPs showed up to 90% encapsulation for different therapeutic agents. Furthermore, the research shows that CNPs provide extended-release patterns, greatly enhancing medication bioavailability especially for hydrophobic compounds. One interesting outcome was the greater drug stability in acidic surroundings, which are common in the stomach, where CNPs turn into a gel and later inflate in the intestine where the drug is released. Moreover, CNPs showed a 2–3-fold improvement in the absorption of encapsulated pharmaceuticals relative to traditional formulations, therefore indicating their capacity to overcome the problems of low oral bioavailability. These nanoparticles’ pH-sensitive character produced a 50–70% increase in drug release at certain pH values, hence maximizing therapeutic results. Significantly less systemic toxicity was seen in the in vivo tests, and at therapeutic dosages there were no noted side effects. Histological study confirmed the biocompatibility and non-toxicity of CNPs, therefore attesting their fit for long-term usage. These results highlight the great potential of CNPs in providing effective, focused, continuous drug release, hence improving therapeutic effectiveness and patient compliance. Full article

Antifungal composite beads were prepared using a methylcellulose, alginate, and ethanol solution with the ionic gelation method and ethanol beads (E). A total of 1.0 mL of clove essential oil (CEO) and 1.0 g of vanillin were added to provide an antifungal effect against Aspergillus flavus and Rhizopus stolonifera. Four bead formulations were prepared: ethanol beads (E), ethanol beads containing CEO (EC), ethanol beads containing vanillin (EV), and ethanol beads containing vanillin and CEO (EVC). Ethanol beads were transparent and spherical, whereas those containing CEO or vanillin were spherical and opaque, with diameters ranging from 2.1 to 2.4 mm. The surface and pores in the polymer matrix were investigated in relation to the encapsulation and release of antifungal agents. The bursting release of ethanol and CEO occurred on the first day. Antifungal assays on potato dextrose agar against Aspergillus flavus and Rhizopus stolonifera showed that beads containing CEO (EC and EVC) provided superior inhibition, particularly at a dosage of 1.0 g. In butter cake preservation tests, packaging the butter cake with a sachet containing 1.0 g of EC or EVC beads can extend the shelf life by two days, delaying visible mold growth from day 5 to day 7 compared to the control. Full article

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by low-grade inflammation, cartilage breakdown, and persistent pain. Despite its prevalence, current therapeutic strategies primarily focus on symptom management rather than modifying disease progression. Monoclonal antibodies and cytokine inhibitors targeting inflammatory pathways, including TNF-α and IL-1, have shown promise but remain limited by inconsistent efficacy and safety concerns. Long-acting biologic therapies—ranging from extended-release formulations, such as monoclonal antibodies and cytokine inhibitors, to gene therapy approaches—have emerged as promising strategies to enhance treatment durability and improve patient outcomes. Extracellular vesicles (EVs) have gained particular attention as a novel delivery platform due to their inherent stability, biocompatibility, and ability to transport therapeutic cargo, including biologics and immunomodulatory agents, directly to joint tissues. This review explores the evolving role of EVs in OA treatment, highlighting their ability to extend drug half-life, improve targeting, and modulate inflammatory responses. Additionally, strategies for EV engineering, including endogenous and exogenous cargo loading, genetic modifications, and biomaterial-based delivery systems, are discussed. Full article

Opacity, an important property of the information flow in discrete-event systems (DESs), characterizes whether the secret information in a system is ambiguous to a passive observer (called an intruder). Observation models play a critical role in the analysis of opacity. In this paper, instead of adopting a fully static observation model or a fully dynamic observation model, we use a novel Orwellian-type observation model to study the verification of the current-state opacity (CSO), where the observability of an unobservable event can be re-interpreted once certain/several specific conditions are met. First, a K-delay Orwellian observation mechanism (KOOM) is proposed as a novel Orwellian-type observation mechanism for extending the existing Orwellian projection. The main characteristics of the KOOM are delaying the inevitable information release and narrowing the release range for historical information to protect the secrets in a system to a greater extent than with the existing Orwellian projection. Second, we formulate the definitions of standard and strong CSO under the KOOM. Finally, we address the verification problem for these two types of opacity by constructing two novel information structures called a standard K-delay verifier and a strong K-delay verifier, respectively. An analysis of the computational complexity and illustrative examples are also presented for the proposed results. Overall, the proposed notions of standard and strong CSO under the KOOM capture the security privacy requirements regarding a delayed release in applications, such as intelligent transportation systems, etc. Full article