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Three-dimensional printing is one of the emerging technologies that is gaining interest from the pharmaceutical industry as it provides an opportunity to customize drugs according to each patient's needs. Combining different active pharmaceutical ingredients, using different geometries, and providing sustained release enhances the effectiveness of medicine. One of the most innovative uses of 3D printing is producing fabrics, medical devices, medical implants, orthoses, and prostheses. This review summarizes the various 3D printing techniques such as stereolithography, inkjet printing, thermal inkjet printing, fused deposition modelling, extrusion printing, semi-solid extrusion printing, selective laser sintering, and hot-melt extrusion. Also, discusses the drug relies profile and its mechanisms, characteristics, and applications of the most common types of 3D printed API formulations and its recent development. Here, Authors also, summarizes the central flow of 3D food printing process and knowledge extension toward personalized nutrition., Competing Interests: Declaration of competing interest There is no conflict of financial interest among the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) presents a significant global health burden, necessitating innovative therapeutic strategies to address its multifaceted challenges. This study explores the potential of Citrus trifoliata extract-loaded chitosan nanoparticles (CTECNPs) as a novel treatment modality for OA. The encapsulation of Citrus trifoliata extract (CTE) within chitosan nanoparticles offers advantages such as enhanced bioavailability, sustained release kinetics, and targeted delivery to affected joints. In vitro evaluations demonstrate the biocompatibility and anti-inflammatory properties of CTECNPs, with significant anti-inflammatory and antioxidative effects observed. Moreover, in vivo studies in an OA-induced mouse model reveal promising therapeutic outcomes, including improvements in histological features and locomotor function. These findings highlight the potential of CTECNPs as a promising therapeutic approach for OA, offering hope for improved patient outcomes and quality of life. Further research is warranted to elucidate additional signaling pathways and potential synergistic effects of CTECNPs in OA management., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.

Nanomaterials cannot only act as active ingredients (AIs), but also adjuvants to encapsulate or attach AIs to improve their fungicidal activity. Herein, a hydrophilic and lipophilic diblock polymer (HLDP) is designed and synthesized to prepare a series of HLDP nano-protectants to explore the best HLDP nano-protectant for anthracnose management. These results demonstrate that the HLDP-CS nano-protectant displays the best control effects on mango anthracnose via the direct pathogen inhibition and amplified plant immune responses. The HLDP can be spontaneously conjugated with CS into nanoscale spherical particles through hydrophobic interaction. The complexation of CS with HLDP remarkably improves the deposition and adhesion of CS droplets on mango leaves. The HLDP can interact with mycelium via electrostatic interaction to damage the cell wall/membrane, which can act as an AI to directly suppress the spore germination and mycelial growth. Meanwhile, HLDP can be applied as an adjuvant for CS to amplify the plant immune responses via accelerating the biosynthesis of secondary metabolites and plant hormones. This work reports the multiple missions for nanomaterials in pathogen control, which proposes a novel strategy for designing nano-protectant with dual-synergistic mechanism., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The lymphatic system plays a crucial role in immune function and the removal of cellular waste. Recent studies have highlighted the presence of primo vessels (PVs) inside lymphatic vessels, distinct from conventional lymphatic tissues, yet their structural and functional characteristics remain poorly understood, particularly PVs inside deep cervical lymphatic vessels (dcLVs) connected to the meningeal lymphatics. We used a combination of Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Alcian Blue (AB) and H&E staining techniques to identify and characterize PVs inside the dcLVs of mice. PVs were identified inside the dcLVs, revealing distinct bundle structures composed of 3 to 5 primo subvessels (sub-PV), with diameters of 5.4 ± 2.4 μm. AFM analyses confirmed the presence of nm-sized pores on the sub-PVs, which may facilitate the absorption and retention of nanoparticles. Rod-shaped nuclei were also observed, further distinguishing PVs from other vascular structures. Our study provides new insights into the structural characteristics of PVs inside dcLVs, suggesting their potential role in targeted drug delivery. However, further research is required to explore the functional implications of these structures, especially their therapeutic applications and roles in various lymphatic regions, including the meningeal lymphatics., Competing Interests: Declarations Competing interests The authors declare no competing interests.All authors have no conflicts of interest relevant to this study to disclose. Approval for animal experiments This research was approved by the Wonkwang University Animal Experiment Ethics Committee (WKU23-48)., (© 2024. The Author(s).)

Microneedle technology has emerged as an advanced method for transdermal drug delivery, which focuses on diverse fabrication techniques to develop microneedles with various models and geometries. This study explores the application of Computer Numerical Control (CNC) milling technology to create microneedle master molds with extremely sharp tips. We examined the effects of two key machining parameters, feed rate and ramp angle, on the tip sharpness of the microneedles. Our results showed that increasing both the feed rate and ramp angle could significantly reduce machining time. However, a higher feed rate also led to larger tip diameters and notable tip defects. Conversely, changes in the ramp angle at a constant feed rate had minimal impact on tip size. We identified an optimal condition balancing cutting time and tip sharpness at a feed rate of 100 mm/min and a ramp angle of 1.5°. Additionally, we assessed the CNC's capability to produce needles with different tip angles. The findings confirm that needles with varying tip angles maintained tip diameters below 10 μm, with needles having a 50° tip angle exhibiting the sharpest tips at approximately 3.3 μm. Further compression, insertion and diffusion tests were conducted to evaluate the performance of needles with different geometries., Competing Interests: Declarations Consent for publication The authors declare that they have provided their consent for publishing this manuscript. Competing interests The authors report no conflicts of interest in this work., (© 2024. Controlled Release Society.)

Introduction: Diabetic retinopathy, a significant trigger for blindness among working age individuals with diabetes, poses a substantial global health challenge. Understanding its underlying mechanisms is pivotal for developing effective treatments. Current treatment options, such as anti-VEGF agents, corticosteroids, laser photocoagulation, and vitreous surgery, have their limitations, prompting the exploration of innovative approaches like nanocapsules based drug-delivery systems. Nanoparticles provide promising solutions to improve drug delivery in ocular medicine, overcoming the complexities of ocular anatomy and existing treatment constraints., Areas Covered: This review explored advanced therapeutic strategies for diabetic retinopathy, focusing on current medications with their limitations, drug delivery methods, device innovations, and overcoming associated barriers. Through comprehensive review, it aimed to contribute to the discovery of more efficient management strategies for diabetic retinopathy in the future., Expert Opinion: In the next five to ten years, we expect a revolutionary shift in how diabetic retinopathy is treated. As we deepen our understanding of oxidative stress and metabolic dysfunction, antioxidants are poised to take center stage in prevention and treatment strategies. Our vision is to create a more integrated approach to diabetic retinopathy management that not only improves patient outcomes but also reduces the risks associated to traditional therapies.

Fibrous scaffolds capable of delivering natural drugs and herbs show great promise for tissue regeneration and wound care, particularly in personalized medicine. This study presents the fabrication and characterization of drug-eluting antibacterial core-shell mats composed of polycaprolactone (PCL) and pectin nanofibers produced through coaxial electrospinning. Berberine chloride (BBR), an herbal compound with antineoplastic, anti-inflammatory, antilipidemic, and antidiabetic properties, served as the model drug. Poly(vinyl alcohol) (PVA) was blended with pectin to enhance the mechanical properties of the core fibers. The shell was modified with two-dimensional Ti 3 C 2 T x (MXene) nanosheets and subjected to covalent and ionic cross-linking. Structural analysis confirmed the successful production of bead-free fibers with diameters ranging from 160 to 350 nm, depending on composition. The PCL core fibers were uniformly coated with a pectin/PVA shell approximately 90 nm thick. The inclusion of BBR and MXene increased the fiber diameter. Drug-release kinetics, modeled by using Korsmeyer-Peppas, revealed a two-stage release mechanism. An initial burst release occurred within the first 24 h (kinetic exponent n = 1.36), followed by sustained release over 2 weeks ( n = 0.48). The release mechanisms were identified as case-II relaxational release in the first stage, transitioning to quasi-Fickian diffusion in the second. Incorporating MXene into the shell further prolonged drug release. The mechanical strength of the scaffolds improved significantly by a factor of 7 and 4 in wet and dry conditions, respectively. In vitro biocompatibility assays using L929 cells demonstrated excellent cell attachment and compatibility. Additionally, antibacterial tests against Escherichia coli showed that the inclusion of MXene enhanced antibacterial activity by 30%. These results suggest that the functional biocomposite scaffolds hold the potential for developing innovative, drug-eluting wound dressings.

Cancer remains a formidable challenge, inflicting profound physical, psychological, and financial burdens on patients. In this context, silica-based nanomaterials have garnered significant attention for their potential in tumor imaging and therapy owing to their exceptional properties, such as biocompatibility, customizable porosity, and versatile functionalization capabilities. This review meticulously examines the latest advancements in the application of silica-based nanomaterials for tumor imaging and therapy. It underscores their potential in enhancing various cancer imaging modalities, including fluorescence imaging, magnetic resonance imaging, computed tomography, positron emission tomography, ultrasound imaging, and multimodal imaging approaches. Moreover, the review delves into their therapeutic efficacy in chemotherapy, radiotherapy, phototherapy, immunotherapy, gas therapy, sonodynamic therapy, chemodynamic therapy, starvation therapy, and gene therapy. Critical evaluations of the biosafety profiles and degradation pathways of these nanomaterials within biological environments are also presented. By discussing the current challenges and prospects, this review aims to provide a nuanced perspective on the clinical translation of silica-based nanomaterials, thereby highlighting their promise in revolutionizing cancer diagnostics, enabling real-time monitoring of therapeutic responses, and advancing personalized medicine.

Topical administration is the commonly preferred method of administering ophthalmic formulations, with the majority of available medications in the form of eye drops or ointments. However, the topical application of ophthalmological medications has less bioavailability and a short residence time because of the physiological and anatomical constraints of the eye, making efficient ophthalmic drug delivery a challenging task. Microfluidic contact lenses have the advantage of delivering drugs into the eye in a controlled and on-demand manner. Here, we showcase the use of hydrogel-embedded microcavities on PDMS-based contact lenses for ocular drug delivery applications. The fabrication technique adopted here is the spontaneous formation of the spherical cavity by hydrogel monomer droplet, followed by the simultaneous thermal curing of hydrogel and PDMS, creating a spherical cavity as small as 150 μm. The spherical cavity is embedded with pH-responsive hydrogel for on-demand drug delivery. The drug loaded in the hydrogel matrix is released into the ocular environment by diffusion. The spherical cavity with a narrow opening restricts the diffusion to a minimum under normal ocular pH conditions(pH > 6). When the ocular pH reduces (pH < 6), the pH-responsive hydrogel inside the spherical cavity deswell and accelerates the drug release.

Positively charged antimicrobial polymers are known to cause severe damage to biological systems, and thus synthetic strategies are urgently required to design next-generation nontoxic cationic macromolecular architectures for healthcare applications. Here, we report a structural-engineering strategy to build cationic linear and star-block copolymer nanoarchitectures having identical chemical composition, molar mass, nanoparticle size, and positive surface charge, yet they differ distinctly in their biological action in breaching prokaryotic species such as E. coli (Gram-negative bacteria) without affecting eukaryotic species like red-blood and mammalian cells. For this purpose, linear and star-block structures are built on a polycaprolactone biodegradable platform having an imidazolium positive handle. Under physiological conditions, the linear architecture exhibits toxicity indiscriminately to all biological species, whereas its star counterpart is remarkably selective in membrane breaching action toward bacteria while maintaining inertness toward eukaryotic species. Confocal microscopy analysis of HPTS fluorescent dye-loaded star-polymer nanoparticles substantiated their antimicrobial action in E. coli . Tissue-penetrable near-infrared fluorescent dye (IR-780) loaded NP aided the in vivo biodistribution analysis and ex vivo quantification of cationic species' accumulations in vital organs in mice. Azithromycin, a clinical water-insoluble macrolide, is delivered from the star platform to accomplish synergistic antimicrobial activity by the combination of bactericidal-bacteriostatic action of the polymer carrier and drug together in a single system.

The era of mucoadhesive polymers has advanced to the next generation, focusing on targeted adhesion of chemical functional groups with mucosa. This work aims to develop boronic acid functionalized polymers, which could facilitate reversible binding with the mucin in the mucosa. Pendant groups of boronic acid were conjugated on the chains of polyvinylpyrrolidone (PVP) via C═N bonding. The evidence from FTIR spectroscopy, XPS analysis, and UV spectroscopy has been used for the confirmation of the chemical conjugation of 3-aminophenyl boronic acid (APBA) to PVP. Boronate ester formation is a pH-dependent process. High p K a values of APBA preferably cause the binding of trigonal-shaped boronic acid with sialic acid groups of mucin. Boronic acid moieties additionally benefited in mucoadhesion in comparison to PVP alone, which is a result of the formation of a five-membered boronate ester complex. The presence of boronic acid moieties enhanced the force of adhesion on porcine buccal mucosal tissue from 13.12 ± 1.52 to 19.04 ± 1.97 g force. Specific binding of the polymer to the mucosal surface caused prolonged adhesion of the polymer to the mucosal surface. A polymer blend of boronic acid functionalized PVP and zein has been explored for its potential for mucoadhesive delivery of propranolol hydrochloride.

The use of highly potent but very toxic antibiotics such as colistin has become inevitable due to the rise of antimicrobial resistance. We aimed for a chemically-triggered, controlled release of colistin at the infection site to lower its systemic toxicity by harnessing the power of click-to-release reactions. Kinetic experiments with nine tetrazines and three dienophiles demonstrated a fast release via an inverse-electron-demand Diels-Alder reaction between trans-cyclooctene (TCO) and the amine-functionalised tetrazine Tz7. The antibiotic activity of colistin against Escherichia coli was masked by TCO units, but restored upon reaction with d-Ubi-Tz, a tetrazine functionalised with the bacterial binding peptide d-Ubi 29-41 . While standard TCO did not improve toxicity against human proximal tubular kidney HK-2 cells, the installation of an aspartic acid-modified TCO masking group reduced the overall charge of the peptide and entry to the kidney cells, thereby dramatically lowering its toxicity. The analog Col-(TCO-Asp) 1 had favourable pharmacokinetic properties in mice and was successfully activated locally in the lung by d-Ubi-Tz in an in vivo infection model, whereas it remained inactive and non-harmful without the chemical trigger. This study constitutes the first example of a systemically acting two-component antibiotic with improved drug tolerability., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

For modulation of cellular behavior, systems that can provide controlled delivery of proteins (soluble signals) over a few hours to a few days are highly desirable. Conventional erosion-controlled systems are inadequate as their degradation spans days to months. Conversely, hydrogels offer quicker release but are limited by a high burst release that can lead to cytotoxicity and rapid depletion of the permeant. To avoid burst release and achieve controlled diffusion of proteins, we propose exploiting electrostatic interactions between the hydrogel matrix and proteins. Here we demonstrate this concept using two disparate hydrogel systems: (1) a chemically cross-linked protein (gelatin) matrix and (2) a physically cross-linked polysaccharide (agarose) matrix and three proteins having different isoelectric points. By introducing fixed charges into the hydrogel matrix using carboxylated agarose (CA), the precise and controlled release of BSA, lactoferrin, and FGF2 over a few hours to days is demonstrated. Using electroendosmosis, we further provide evidence for a clear role for CA in modulating the release. Our findings suggest that the paradigm presented herein has the potential to significantly enhance the design of hydrogel systems for the delivery of proteins and RNA therapeutics for vaccines and biomedical applications ranging from tissue engineering to functional coatings for medical devices.

The success of gene therapy hinges on the effective encapsulation, protection, and compression of genes. These processes deliver therapeutic genes into designated cells for genetic repair, cellular behavior modification, or therapeutic effect induction. However, quantifying the encapsulation efficiency of small molecules of interest like DNA or RNA into delivery carriers remains challenging. This work shows how super-resolution microscopy, specifically direct stochastic optical reconstruction microscopy (dSTORM), can be employed to visualize and measure the quantity of DNA entering a single carrier. Utilizing pNIPAM/bPEI microgels as model nano-carriers to form polyplexes, DNA entry into the carrier is revealed across different charge ratios at temperatures below and above the volume phase transition of the microgel core. The encapsulation efficiency also depends on DNA length and shape. This work demonstrates the uptake of the carrier entity by primary derived macro-phages and showcases the cell viability of the polyplexes. The study shows that dSTORM is a potent tool for fine-tuning and creating polyplex microgel carrier systems with precise size, shape, and loading capacity at the individual particle level. This advancement shall contribute significantly to optimizing gene delivery systems., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Ischemic stroke (IS), accounting for 87 % of stroke incidences, constitutes a paramount health challenge owing to neurological impairments and irreversible tissue damage arising from cerebral ischemia. Chief among therapeutic obstacles are the restrictive penetration of the blood-brain barrier (BBB) and insufficient targeting precision, hindering the accumulation of drugs in ischemic brain areas. Motivated by the remarkable capabilities of natural membrane-based delivery vehicles in achieving targeted delivery and traversing the BBB, thanks to their biocompatible architecture and bioactive components, numerous membrane-engineered systems such as cells, cell membranes and extracellular vesicles have emerged as promising platforms to augment IS treatment efficacy with the help of nanotechnology. This review consolidates the primary pathological manifestations following IS, elucidates the unique functionalities of natural membrane drug delivery systems (DDSs) with nanotechnology, as well as delineates the structural characteristics of various natural membranes alongside rational design strategies employed. The review illuminates both the potential and challenges encountered when employing natural membrane DDSs in IS drug therapy, offering fresh perspectives and insights for devising efficacious and practical delivery systems tailored to IS intervention., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

We have developed an innovative peripheral nerve tissue repair approach by designing biomimetic microparticles loaded with cannabidiol (CBD) using horseradish peroxidase-mediated crosslinking within a microfluidic device. This method utilizes a water-in-oil emulsion system where a mixture of phenol-substituted hyaluronic acid (HAPh), CBD, and laccase is channeled into oil flow, forming hydrogel microparticles. The physical properties, such as their swelling rate, mechanical strength, and the sustained release of CBD, emphasize their potential in tissue engineering and drug delivery applications. Cellular proliferation studies within the microparticles demonstrate their cytocompatibility, making them suitable for developing microtissues. The microparticles also served as a controlled release mechanism for CBD-targeted delivery to the injured locations, showcasing the effectiveness and ability to aid in the regeneration of the sciatic nerve tissue. In vivo, histopathological analysis of treated sciatic nerve injuries showed enhanced axonal restoring and remyelination with HAPh microparticles containing CBD in contrast to control groups. Furthermore, microparticles enhanced various functional aspects of locomotor activities, such as functional sciatic index (SFI) values, response to heat stimulation, and muscle mass retention. In conclusion, results indicate that these composite biomimetic microparticles with CBD effectively promote nerve structural restoration and increase the reconstruction process in a sciatic nerve injury model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Garlic protein is one of the main components of garlic. It has several beneficial characteristics. This study aimed to characterize a double crosslinked hydrogel formed with alginate, calcium ions (Ca 2+ ), and garlic protein hydrolysates (GPH), and to develop hydrogel beads for targeted delivery of bioactive constituents to the gastrointestinal tract., Results: The results indicated that the degree of GPH hydrolysis was approximately 3% following trypsin treatment. The inner structure of the double crosslinked hydrogel showed a honeycomb pattern, with solid-like gel rheology and improved texture properties at a 4% (w/v) GPH concentration. The GPH-based hydrogel beads demonstrated pH sensitivity, swelling in near-neutral and alkaline environments, and the encapsulated paclitaxel (PTX) exhibited an amorphous phase with preferential release in intestinal conditions. The GPH group also achieved greater drug encapsulation efficiency than a soy protein hydrolysate (SPH) group, and proteomic analysis suggested that lower molecular weight and peptide charge favored the formation of peptide-integrated double crosslinking hydrogels., Conclusion: This work indicated that GPH was helpful and could inspire the development of drug delivery systems involving GPH with the required mechanical strength and target-release properties. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Antimicrobial photodynamic therapy (aPDT) emerges as a viable treatment strategy for infections resistant to conventional antibiotics. A complex interplay of factors, including intracellular photosensitizer (PS) accumulation, photochemical reaction type, and oxygen levels, determines the efficacy of aPDT. Recent progress includes the development of modified PSs with enhanced lipophilicity and target-specific strategies to improve bacterial cell wall penetration and targeting. Nanotechnology-based approaches, such as using nanomaterials for targeted PS delivery, have shown promise in enhancing aPDT efficacy. Advancements in light delivery methods for aPDT, such as transillumination of large lesions and local light delivery using fiber optic techniques, are also being explored to optimize treatment efficacy in clinical settings. The limited number of animal models and clinical trials specifically designed to assess the efficacy of aPDT for lung infections highlights the need for further research in this critical area. The potential prospects of aPDT for lung tissue infections originating from antibiotic-resistant bacterial infections are also discussed in this review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pulmonary delivery of small interfering RNAs (siRNAs) is an effective treatment for acute lung injury (ALI), which can modulate the expression of pro-inflammatory cytokines and alleviate the symptoms of ALI. However, the rapid degradation of siRNA in vivo and its limited ability to target and validate cells are important challenges it faces in clinical practice. In this work, we developed neutrophil membrane-coated Poly (lactic-co-glycolic acid) nanoparticles loaded with TLR4 siRNA (si-TLR4) (Neutrophil-NP-TLR4), which can target both inflammatory and macrophage cells to alleviate the pulmonary inflammation in lipopolysaccharide (LPS)-induced ALI mice. These Neutrophil-NP-TLR4 effectively reduce the TNF-α and IL-1β expressions both in vitro and in vivo. Meanwhile, they also reduced the expression of TLR4, and its downstream genes including TNF receptor-associated factor 6 (TRAF6), X-linked inhibitor of apoptosis protein (XIAP), and Nuclear Factor kappa-B (NF-κB), but elevated the levels of Aquaporin 1 (AQP1) and Aquaporin 5 (AQP5). Moreover, the Neutrophil-NP-TLR4 precisely targets the inflammatory site to attenuate the lung injury without causing toxicity to normal tissue. This system provides a promising approach to effective delivery of siRNA to precisely treat the ALI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Self-assembled peptide nanoparticles are unique stimuli responsive biodegradable materials with applications in biomedicines as delivery carriers and imaging agents. This study investigates the controlled self-assembly of chicken Angiogenin 4 derived immunomodulatory macrocyclic peptide (mCA4-5) in the presence of an inert amphipathic stabilizing peptide and as a function of pH, temperature and presence of ions to yield optically active, physiologically stable and biodegradable peptide nanoparticles. The photoluminescent peptide nanoparticles (PLPNs) produced were characterized for the size, surface charge, optical properties and crystallinity. The carvacrol loaded nanoparticles prepared by facile encapsulation of the drug during the self-assembly process were evaluated for the drug release efficacies, as a function of pH and in the presence of reducing agent. Carvacrol loaded, physiologically stable PLPNs obtained with high conversion efficacy were highly effective against planktonic bacteria and bacterial biofilms and efficiently eradicated intracellular bacteria in infected macrophages and fibroblast. Furthermore, the drug-loaded nanoparticles exhibited significant antioxidant activities and immunomodulatory effects, highlighting their multifunctional therapeutic potential., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Alzheimer's disease (AD) is a severe neurodegenerative disorder, and the current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exos) have garnered significant attention due to their unique biological properties, showcasing tremendous potential as an acellular alternative therapy for AD. MSC-Exos exhibit excellent biocompatibility and low immunogenicity, enabling them to effectively cross the blood-brain barrier (BBB) and deliver therapeutic molecules directly to target cells. They are highly efficacious in delivering nucleic acid-based drugs. Moreover, the production process of MSC-Exos benefits from a high proliferation capacity and multilineage differentiation potential, allowing for production while maintaining a stable composition. Despite the significant theoretical advantages of MSC-Exos, their clinical use still faces multiple challenges, including cross-contamination during isolation and purification processes, the complexity of their components, and the presence of potential adverse paracrine factors. Future research needs to focus on optimizing separation and purification techniques, enhancing delivery methods to improve therapeutic efficacy, and performing detailed analyses of the components of MSC-Exos. In summary, MSC-Exos hold promise as an effective option for the treatment of AD and other neurodegenerative diseases, driving their clinical research and use in related fields.

The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dacarbazine (DTIC) is the drug of choice for melanoma treatment, but its systemic administration is related to several adverse effects. Here, DTIC topical delivery stimulated by iontophoresis is proposed to overcome such drawbacks. Hence, this work analyzed the impact of anodal iontophoresis on DTIC cutaneous delivery to provide an innovative topical alternative for melanoma treatment. The electrical stability of the drug was evaluated prior to the iontophoretic experiments, which demonstrated the need to add an antioxidant to the drug formulation. DTIC cutaneous permeation was evaluated in vitro for 6 h using three current densities (0.10, 0.25, and 0.50 mA/cm 2 ). In addition, the effect of DTIC against skin cancer cells (MeWo and WM164) was investigated for 72 h of exposure to the drug. Iontophoresis stimulated skin drug permeation compared to the passive control. However, the antioxidant presence reduced DTIC permeation under the lower currents of 0.10 and 0.25 mA/cm 2 , which was compensated by increasing the current density to 0.50 mA/cm 2 . At 0.50 mA/cm 2 , iontophoresis enhanced topical cutaneous drug permeation 7-fold (p < 0.05) compared to the passive control. DTIC showed a concentration-dependent antiproliferative effect on melanoma cell lines. Thus, iontophoresis intensifies DTIC skin penetration in concentrations that can reduce cell viability and induce cell death. In conclusion, DTIC cutaneous delivery mediated by iontophoresis is a promising approach for treating melanomas and other skin tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Combination of nanoagents with radiations has opened up new perspectives in cancer treatment, improving both tumor diagnosis and therapeutic index. This work presents the first investigation of an innovative strategy that combines porous metal-organic frameworks (nanoMOFs) loaded with the anti-cancer drug Gemcitabine monophosphate (GemMP) and particle therapy-a globally emerging technique that offers more precise radiation targeting and enhanced biological efficacy compared to conventional radiotherapy. This radiochemotherapy has been confronted with two major obstacles limiting the efficacy of therapeutics when tested in vivo: (i) the presence of hypoxia, one of the most important causes for radiotherapy failure and (ii) the presence of a microenvironment, main biological barrier to the direct penetration of nanoparticles into cancer cells. On the one hand, this study explore the effects of hypoxia on drug delivery systems in combination with radiation, demonstrating that GemMP-loaded nanoMOFs significantly enhance the anticancer efficacy of particle therapy under both normoxic (pO 2  = 20 %) and hypoxic (pO 2  = 0.5 %) conditions. Notably, the presence of GemMP-loaded nanoMOFs allows the irradiation dose to be reduced by 1.4-fold in normoxia and at least 1.6-fold in hypoxia, achieving the same cytotoxic effect (SF=10 %) as carbon or helium ions alone. Synergistic effects between GemMP-loaded nanoMOFs and radiations have been observed and quantified. On the other hand, we also highlighted the ability of the nanoMOFs to diffuse through an extracellular matrix and accumulate in cells. An higher effect of the encapsulated GemMP than the free drug was observed, confirming the key role of the nanoMOFs in transporting the active substance to the cancer cells as a Trojan horse. This paves the way to the design of "all-in-one" nanodrugs where each component plays a role in the optimization of cancer therapy to maximize cytotoxic effects on hypoxic tumor cells while minimizing toxicity on healthy tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Erythrocytes have gained popularity as a natural option for in vivo drug delivery due to their advantages, which include lengthy circulation times, biocompatibility, and biodegradability. Consequently, the drug's pharmacokinetics and pharmacodynamics in red blood cells can be considerably up the dosage. Here, we provide an overview of the erythrocyte membrane's structure and discuss the characteristics of erythrocytes that influence their suitability as carrier systems. We also cover current developments in the erythrocyte-based nanocarrier, which could be used for both active and passive targeting of disease tissues, particularly those of the reticuloendothelial system (RES) and cancer tissues. We also go over the most recent discoveries about the in vivo and in vitro uses of erythrocytes for medicinal and diagnostic purposes. Moreover, the clinical relevance of erythrocytes is discussed in order to improve comprehension and enable the potential use of erythrocyte carriers in the management of various disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Breast cancer (BC) is the most common malignancy among females worldwide, and its high metastasis rates are the leading cause of death just after lung cancer. Currently, tamoxifen (TAM) is a hydrophobic anticancer agent and a selective estrogen modulator (SERM), approved by the FDA that has shown potential anticancer activity against BC, but the non-targeted delivery has serious side effects that limit its ubiquitous utility. Therefore, releasing anti-cancer drugs precisely to the tumor site can improve efficacy and reduce the side effects on the body. Nanotechnology has emerged as one of the most important strategies to solve the issue of overdose TAM toxicity, owing to the ability of nano-enabled formulations to deliver desirable quantity of TAM to cancer cells over a longer period of time. In view of this, use of fluorescent carbon nanoparticles in targeted drug delivery holds novel promise for improving the efficacy, safety, and specificity of TAM therapy. Here, we synthesized biocompatible carbon nanoparticles (CNPs) using chitosan molecules without any toxic surface passivating agent. Synthesized CNPs exhibit good water dispersibility and emit intense blue fluorescence upon excitation (360 nm source). The surface of the CNPs has been functionalized with folate using click chemistry to improve the targeted drug uptake by the malignant cell. The pH difference between cancer and normal cells was successfully exploited to trigger TAM release at the target site. After six hours of incubation, CNPs released ∼ 74 % of the TAM drug in acidic pH. In vitro, studies have also demonstrated that after treatment with the synthesized CNPs, significant inhibition of the tumor growth could be achieved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chitosan is a natural polymer derived from chitin. It has significant applications in various fields due to its unique physicochemical properties, biocompatibility, and biodegradability. These important properties of chitosan make it an attractive candidate for various anti-cancer activities and biomedical applications, including tissue engineering. This review emphasizes the latest literature on anticancer applications of chitosan derivatives and in-depth study of biomedical applications. This review highlights the importance of biomedical applications and anti-cancer activities like breast, liver, colon, gastric, melanoma, colorectal, cervical, oral, and lymphoma cancer. Currently, there is a notable absence of recent reviews that comprehensively address these aspects such as Alejandro Elizalde-Cárdenas, et al. 2024, focuses only on Biomedical applications of Cs and its derivatives (Elizalde-Cárdenas et al., 2024). Jingxian Ding, et al. 2022 discussed the applications of Cs in some Cancer treatments (Mabrouk et al., 2024). However, our article aims to provide a comprehensive overview of the latest advancements in Cs derivatives in both fields. This manuscript is designed with proper diagrams, flow sheets and summarized tables to enhance the understanding of the reader. It also highlights recent advancements in the development of various chitosan derivatives, offering a comprehensive perspective for researchers and practitioners to further progress in biomedical and anticancer technologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Polymers have been integral to the advancement of biomedicine, owing to their exceptional versatility and functionality. Among these, polyvinyl alcohol (PVA) and chitosan both natural polymers stand out for their remarkable biocompatibility, biodegradability, and unique properties. This review article provides a comprehensive examination of the diverse applications of PVA and chitosan in three pivotal areas: tissue engineering, drug delivery, and biosensors. In tissue engineering, the discussion centres on how PVA and chitosan are engineered into scaffolds that not only support cell growth and differentiation but also promote tissue regeneration by closely mimicking the extracellular matrix. These scaffolds offer the necessary mechanical strength and adaptability for various biomedical applications. For drug delivery, the article delves into the development of sophisticated controlled release systems and targeted drug carriers, highlighting the polymers' customizable properties and their mucoadhesive nature, which make them highly effective across multiple drug delivery methods. Furthermore, the potential of PVA and chitosan in biosensor technology is explored, particularly their ability to interact with biomolecules and their intrinsic conductivity attributes that are essential for creating sensitive, reliable, and biocompatible sensors for medical diagnostics. By synthesizing recent research findings and suggesting future research directions, this review underscores the versatility and critical role of PVA and chitosan in pushing the boundaries of biomedical innovation. It offers valuable insights for researchers and scientists dedicated to advancing healthcare through the application of these natural polymers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This research investigates the formulation of a nanogel complex using pectin and poly(acrylic acid) (PAAc) to encapsulate rutin. The nanogel's pH-responsive behavior and its potential as a targeted drug delivery platform are investigated. The gamma irradiation-induced crosslinking mechanism is elucidated, highlighting its role in creating a stable three-dimensional network structure within the polymer matrix. Fourier transform infrared spectroscopy analysis sheds light on the molecular interactions within rutin and the nanogel-rutin complex. The pH-responsive behavior of the nanogel is explored, showcasing its ability to release rutin selectively in response to pH variations and displaying high physical and chemical stability. Transmission electron microscopy imaging provides visual insights into nanogel morphology and interactions. The cumulative drug content from the nanogel was 86.14 ± 2.61%. The pH-dependent release profile of the nanogel was examined, demonstrating selective rutin release in response to varying pH levels. Cytotoxicity studies were conducted against four human cancer cell lines-HepG2, A549, MCF-7, and HCT-116 showing significant reductions in IC 50 values, indicating enhanced therapeutic efficacy. Additionally, molecular docking studies revealed strong binding interactions of rutin with VEGFR-2 and EGFR T790M . Our nanogel compound 5 significantly reduced the IC 50 values for HepG2, A549, MCF-7, and HCT-116 cells by 58.19%, 81.29%, 71.81%, and 67.16%, respectively. Furthermore, it lowered the IC 50 values for VEGFR-2 and EGFR T790M by 29.66% and 68.18%, respectively., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Emulsion gels with specific rheological properties have widespread applications in foods, cosmetics, and biomedicines. However, the constructions of water-in-oil emulsion gels are still challenging, due to the limited interactions available in the continuous oil phase. Here, a versatile strategy is developed to prepare a new type of emulsion gels, called Jammed Pickering emulsion gels (JPEGs). In the JPEG system, SiO 2 NPs in the oil phase serve as colloidal surfactants to stabilize water-in-oil Pickering emulsions, while positively-charged NH 2 -PEG-NH 2 molecules in the water phase cross-link negatively-charged SiO 2 NPs at the water/oil interface, making NP-stabilized water droplets hard to deform and thus jamming the emulsion system to form emulsion gels. The strategy to prepare JPEGs is versatile and applicable to diverse oil phases. The designed JPEGs possess many advantages, including good biocompatibility for widespread applications, shear-thinning rheological properties for easy processing, good stability Over a wide temperature range and Against centrifugation, good adhesion to wet tissues for tissue engineering, and well-controlled sustained release Under intestinal conditions. The developed JPEGs are demonstrated to be a promising delivery platform and the strategy to achieve JPEGs will trigger more innovations of material design., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Liver fibrosis is a common stage of various chronic liver diseases, often developing into liver cirrhosis, and even liver cancer. Activated hepatic stellate cells (aHSCs) have been shown to promote the development of liver fibrosis. Therefore, dual-targeted combination therapy for liver may be an effective strategy for the treatment of liver fibrosis., Purpose: In this study, the novel nanostructured lipid carriers (GA&GalNH 2 -DC-NLCs) were prepared for Dehydrocavidine (DC), glycyrrhetinic acid (GA) and galactose-PEG 2000 -NH 2 (GalNH 2 ) were selected as targeted ligand-modified nanostructured lipid carriers (NLCs), which enables dual-targeting to the liver for the treatment of liver fibrosis., Study Design: To study the targeting effect of GA&GalNH 2 -DC-NLCs on liver and its therapeutic effect on liver fibrosis, we established aHSC-T6 cell model and rat model of liver fibrosis for study., Results: GA&GalNH 2 -DC-NLCs promoted drug liver targeting efficiency and apoptosis rate by upregulating the expression of Bax. It showed that compared with no and/or GA-modified NLCs and GalNH 2 -modified NLCs, GA&GalNH 2 -DC-NLCs exhibited less extracellular matrix (ECM) deposition, induced apoptosis of aHSCs, and stronger anti-fibrosis effects in vivo. This may be due the fact that GA or GalNH 2 -modifified NLCs simultaneously block HSCs activation and inhibit the IL-6/STAT3 pathway., Conclusion: GA&GalNH 2 -DC-NLCs is thus a potential strategy for liver fibrosis treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Magnetic microrobots, designed to navigate the complex environments of the human body, show promise for minimally invasive diagnosis and treatment. However, their clinical adoption faces hurdles such as biocompatibility, precise control, and intelligent tracking. Here a novel formulation (referred to water-stable magnetic lipiodol micro-droplets, MLMD), integrating clinically approved lipiodol, gelatin, and superparamagnetic iron oxide nanoparticles (SPION) with a fundamental understanding of the structure-property relationships is presented. This formulation demonstrates multiple improved properties including flowability, shape adaptability, efficient drug loading, and compatibility with digital subtraction angiography (DSA) imaging in both in vitro and in vivo experiments. This enables the MLMD as a versatile tool for image-guided therapy, supported by a close-looped magnetic navigation system featuring artificial intelligence (AI)-driven visual feedback for autonomous control. The system effectively performs navigational tasks, including pinpointing specific locations of MLMD, recognizing and avoiding obstacles, mapping and following predetermined paths, and utilizing magnetic fields for precise motion planning to achieve visual drug delivery. The MLMD combines magnetic actuation with an AI-directed close-looped navigation, offering a transformative platform for targeted therapeutic delivery., (© 2024 Wiley‐VCH GmbH.)

Covalent organic frameworks (COFs) have emerged as a distinguished class of porous materials. Owing to their ability to be constructed through covalent bonds involving light elements, such as hydrogen, boron, carbon, nitrogen, and oxygen, COFs offer greater stability and lower cytotoxicity than metal organic frameworks do, addressing critical limitations in in vivo applications. Their unique attributes, such as high surface area, customizable pore sizes, and versatile surface functionalities, make them ideal for various biomedical applications. This review aims to provide an overview of the recent advancements in modern COFs for biomedical uses. First, a variety of methods for the synthesis of COFs are outlined, which ensures their suitability for medical use. Next, we delve into innovative biomedical applications, emphasizing their role in disease diagnostics and therapies. Finally, challenges, such as clinical translation, biocompatibility, and controlled drug release, are critically discussed, providing comprehensive insight into the potential of COFs in revolutionizing biomedical technologies. Overall, this review offers a comprehensive overview of COFs' capabilities and future prospects in enhancing biomedical technologies., (© 2024 Wiley‐VCH GmbH.)

Central nervous system diseases negatively affect patients and society. Providing successful noninvasive treatments for these diseases is challenging because of the presence of the blood-brain barrier. While protecting the brain's homeostasis, the barrier limits the passage of almost all large-molecule drugs and most small-molecule drugs. A noninvasive method, nose-to-brain delivery (N2B delivery) has been proposed to overcome this challenge. By exploiting the direct anatomical interaction between the nose and the brain, the drugs can reach the target, the brain. Moreover, the drugs can be encapsulated into various drug delivery systems to enhance physicochemical characteristics and targeting success. Many preclinical data show that this strategy can effectively deliver biopharmaceuticals to the brain. Therefore, this review focuses on N2B delivery while giving examples of different drug delivery systems suitable for the applications. In addition, we emphasize the importance of the effective delivery of monoclonal antibodies and RNA and stress the recent literature tackling this challenge. While giving examples of nanotechnological approaches for the effective delivery of small or large molecules from the current literature, we highlight the preclinical studies and their results to prove the strategies' success and limitations., (Copyright © 2024, Akpinar Adscheid et al.)

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, making traditional hormone and targeted therapies ineffective. Chemotherapy remains the primary treatment for TNBC; however, it has failed to adequately address the high rates of recurrence and metastasis, underscoring the urgent need for new therapeutic strategies. This study investigates Saikosaponin A (SSA), a compound extracted from traditional Chinese medicine, for its potential to enhance the efficacy of doxorubicin (DOX) chemotherapy while reducing TNBC metastasis and mitigating DOX-induced cardiotoxicity. We first confirmed SSA's cardioprotective effects against DOX-induced cardiotoxicity, highlighting its potential as an adjunctive therapy for TNBC chemotherapy. Subsequently, through network pharmacology analysis, we identified that SSA may inhibit TNBC progression and metastasis by downregulating integrin β3, a key regulatory factor in tumor development. This was further validated through both in vivo and in vitro experiments. To address the poor bioavailability of SSA, we developed a novel drug delivery system utilizing hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for the co-delivery of SSA and DOX. This nano-drug system exhibited excellent stability and high drug-loading capacity, with loading efficiencies of 40.07 % for SSA and 43.07 % for DOX. After 24 h of nano-drug administration, the DOX concentration in the group using the nano-delivery system was 5.01 times higher than control group, demonstrated enhanced tumor-targeting capability. Furthermore, after 14 days of treatment, the tumor volume was reduced by 80.8 % compared to the control group, indicating significantly improved therapeutic efficacy (all P < 0.05). This study systematically evaluates the potential of this dual drug-loaded nanocarrier in improving TNBC treatment, reducing DOX-induced cardiotoxicity, and inhibiting metastasis, offering a novel therapeutic approach that integrates traditional medicine with advanced nanotechnology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Psoriasis is a chronic autoimmune skin disease with a worldwide prevalence of 1-3 % results from uncontrolled proliferation of keratinocytes and affects millions of people. While there are various treatment options available, some of them may come with potential side effects and limitations. Recent research has shown that using bioactive compounds that originate from natural sources with a lower risk of side effects are relatively useful in safe management psoriasis. Bioactive compounds are molecules that are naturally available with potential therapeutic efficacy. Some of bioactive compounds that have shown promising results in the management of psoriasis include curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, etc., possess anti-inflammatory, antioxidant, immunomodulatory, and anti-proliferative properties, with capabilities to suppress overall pathogenesis of psoriasis. Moreover, these bioactive compounds are generally considered as safe and are well-tolerated, making them potential options for long-term use in the management of various conditions linked with psoriasis. In addition, these natural products may also offer a more holistic approach to treat the disease, which is appealing to many patients. This review explores the bioactive compounds in mitigation of psoriasis either in native or incorporated within novel drug delivery. Moreover, recent clinical findings in relation to natural product usage have been also explored., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

This study investigates the enhancement of benzylpenicillin's antibacterial properties using nanomedicine, specifically by developing benzylpenicillin nanoemulsions. To address the escalating issue of bacterial resistance, we employed the advanced techniques Raman spectroscopy and atomic force microscopy to analyze the nanoemulsions' molecular structure and characteristics. We then evaluated the impact of these nanoemulsions on nitric oxide production by macrophages to deternine their potential to modulate inflammatory responses. We further assessed the antibacterial effectiveness of the nanoparticles against the pathogens Streptococcus pyogenes (Group A Streptococcus) and Streptococcus agalactiae (Group B Streptococcus). The results of antibiograms showed significant efficacy against Gram-positive bacteria, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, confirming their bactericidal potential. The investigation into the mechanism of action suggested substantial disruption to bacterial membrane integrity, underscoring a possible mode of antibacterial activity. Overall, the study provides valuable insights into the synergistic relationship between antibiotics and nanoparticles. In particular, it demonstrates the potential of benzylpenicillin nanoparticles to enhance the antimicrobial efficacy and influence inflammatory responses obtained by evaluating nitrite, IL-6 and TNF-α, offering promising avenues for future clinical applications and strategies to combat bacterial resistance., (Copyright © 2024. Published by Elsevier Masson SAS.)

Genipin, a precursor of dietary blue pigment, is a promising alternative for industrial applications in food and health. Due to its ability to simultaneously satisfy biosafety requirements and provide crosslinking effects, genipin has attracted considerable attention for food and biomedical applications. In this review, we attempt to shed light on the progress in genipin research using scientometrics. Based on this scientometric discovery, we reviewed the use of genipin-crosslinked films for fruit packaging in food science. Genipin-crosslinked hydrogels used for drug delivery include natural, chemical, and protein delivery systems. Genipin-crosslinked hydrogels for tissue engineering primarily include materials used for tissue regeneration and repair. Genipin-crosslinked hydrogels are used in wound dressings and wound closure. This review provides a scientometric perspective to facilitate future research and development of genipin for food science, drug delivery, tissue engineering, and wound healing., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The field of nanomedicine is undergoing a seismic transformations with the rise of nanosimilars, reshaping the pharmaceutical landscape and expanding beyond traditional innovators and generic manufacturers. Nanodrugs are increasingly replacing conventional therapies, offering improved efficacy and safety, while the demand for follow-on products drives market diversification. However, the transition from preclinical to clinical stages presents challenges due to the complex biopharmaceutical behavior of nanodrugs. This review highlights the integration of Quality-by-Design (QbD), in vitro-in vivo correlations (IVIVCs), machine learning, and Model-Informed Drug Development (MIDD) as key strategies to address these complexities. Additionally, it discusses the role of high-throughput processes in the optimization of the nanodrug development pipelines. Covering generations of delivery systems from liposomes to RNA-loaded nanoparticles, this review underscores the evolving market dynamics driven by recent advances in nanomedicine., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diabetes and obesity have emerged as major global health concerns. Glucagon-like peptide-1 (GLP-1), a natural incretin hormone, stimulates insulin production and suppresses glucagon secretion to stabilize and reduce blood glucose levels and control appetite. The therapeutic use of GLP-1 receptor agonists (e.g., semaglutide) has transformed the standard of care in recent years for treating type 2 diabetes and reversing obesity. The native GLP-1 sequence has a very short half-life, and therapeutic advances have come from molecular engineering to alter the pharmacokinetic profile of synthetic GLP-1 receptor agonists to enable once-weekly administration, reduce the frequency of injection, and improve adherence. Efforts to further extend this profile would offer additional convenience or enable entirely different treatment modalities. Here, an injectable GLP-1 receptor agonist depot is engineered through integration of a prosthetic self-assembling peptide motif to enable supramolecular nanofiber formation and hydrogelation. This supramolecular GLP-1 receptor agonistic (PA-GLP1) offers sustained release in vitro for multiple weeks, supporting long-lasting therapy. Moreover, in a rat model of type 2 diabetes, a single injection of the supramolecular PA-GLP1 formulation achieved sustained serum concentrations for at least 40 days, with an overall reduction in blood glucose levels and reduced weight gain, comparing favorably to daily injections of semaglutide. The general and modular approach is also extensible to other next-generation peptide therapies. Accordingly, the formation of supramolecular nanofiber depots offers a more convenient and long-lasting therapeutic option to manage diabetes and treat metabolic disorders.

Glioblastoma multiforme (GBM) represents one of the most prevailing and aggressive primary brain tumors among adults. Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood-brain barrier (BBB). Nanotechnology has emerged as a promising avenue for GBM treatment, offering biosafety, sustained drug release, enhanced solubility, and improved BBB penetrability. In this review, a comprehensive overview of recent advancements in nanocarrier-based drug delivery systems for GBM therapy is emphasized. The conventional and novel treatment modalities for GBM and the potential of nanocarriers to overcome existing limitations are comprehensively covered. Furthermore, the updates in the clinical landscape of GBM therapeutics are presented in addition to the current status of drugs and patents in the same context. Through a critical evaluation of existing literature, the therapeutic prospect and limitations of nanocarrier-based drug delivery strategies are highlighted offering insights into future research directions and clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Efficient retention of drugs at tumor sites was always desirable to maximize therapeutic functions, yet the main concern is the dynamic blood clearance induced fast removal from localized lesion. Herein, a tumor microenvironment activated covalently conjugation (self- and proximal conjugation) of tyramine modified Pt nanoclusters (PCMT NPs) was constructed by in situ produced radical hooks, leading to efficient accumulation of PCMT NPs at tumor sites. Such accumulation further aggravated the oxidative stress and provoked autophagy of tumor cells via activating the caspase-3 pathway mediated massive apoptosis, thereby stimulating immunogenic cell death (ICD). As verified by in vivo results, the PCMT NPs effectively suppressed primary and distant tumor growth (with an inhibition rate of 99%) while eliciting immunotherapeutic responses. As such, a new paradigm for boosting drug retention was provided, which enabled specific tumor treatment with synergistic therapeutic outcomes.

Breast cancer (BC) bone metastasis poses a significant clinical challenge due to its impact on patient prognosis and quality of life. Curcumin (CUR), a natural polyphenol compound found in turmeric, has shown potential in cancer therapy due to its anti-inflammatory, antioxidant, and anticancer properties. However, its metabolic instability and hydrophobicity have hindered its clinical applications, leading to a short plasma half-life, poor absorption, and low bioavailability. To enhance the drug-like properties of CUR, nanotechnology-based delivery strategies have been employed, utilizing polymeric, lipidic, and inorganic nanoparticles (NPs). These approaches have effectively overcome CUR's inherent limitations by enhancing its stability and cellular bioavailability both in vitro and in vivo. Moreover, targeting molecules with high selectivity towards bone metastasized breast cancer cells can be used for site specific delivery of curcumin. Alendronate (ALN), a bone-seeking bisphosphonate, is one such moiety with high selectivity towards bone and thus can be effectively used for targeted delivery of curcumin loaded nanocarriers. This review will detail the process of bone metastasis in BC, elucidate the mechanism of action of CUR, and assess the efficacy of nanotechnology-based strategies for CUR delivery. Specifically, it will focus on how these strategies enhance CUR's stability and improve targeted delivery approaches in the treatment of BC bone metastasis., Competing Interests: Declarations Ethics approval and consent to participate There was no need for this research because it was a review, and no volunteers were involved. Consent for publication All authors have consented to publish this work in Discover Nano journal. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

The existing and emerging demand for materials for life and health has contributed to the cultivation and development of respective markets. Nevertheless, the current generation of biomedical materials has yet to fully satisfy the clinical requirements of the market, which is still in its relative infancy. Research and development in this area must be prioritized in light of the pivotal role of new life and health materials in the biological field. Among many life and health materials, GQDs, an emerging nanomaterial, exhibit considerable promise in the biomedical field, primarily due to their exceptional properties. Furthermore, the direct preparation and functionalization of GQDs have facilitated the development of specific functional composites based on GQDs. The biological applications of GQDs are undergoing rapid growth, which makes it necessary to publish a review article presenting the latest advances in this field. This review provides an overview of the significant advances in synthesizing GQDs, the techniques employed for structural characterizations, and the properties that have been elucidated. Furthermore, it presents recent findings on applying GQDs in antimicrobial, anticancer, biosensing, drug delivery, and bioimaging applications. Finally, it explores the potential of GQDs in biomedicine and biotechnology, highlighting the current challenges that remain to be addressed., (© 2024 The Chemical Society of Japan and Wiley-VCH GmbH.)

Myocardial infarction is one of the leading cause of cardiovascular death worldwide. Invasive interventional procedures and medications are applied to attenuate the attacks associated with ischemic heart disease by reestablishing blood flow and restoring oxygen supply. However, the overactivation of inflammatory responses and unsatisfactory drug delivery efficiency in the infarcted regions prohibit functional improvement. Here, a nanoengineered monocyte (MO)-based biohybrid system, referred to as CTAs @MOs, for the heart-targeted delivery of combinational therapeutic agents (CTAs) containing anti-inflammatory IL-10 and cardiomyogenic miR-19a to overcome the limitation of malperfusion within the infarcted myocardium through a polyphenol-mediated interfacial assembly, is reported. Systemic administration of CTAs@MOs bypasses extensive thoracotomy and intramyocardial administration risks, leading to infarcted heart-specific accumulation and sustained release of therapeutic agents, enabling immunomodulation of the proinflammatory microenvironment and promoting cardiomyocyte proliferation in sequence. Moreover, CTAs@MOs, which serve as a cellular biohybrid-based therapy, significantly improve cardiac function as evidenced by enhanced ejection fractions, increased fractional shortening, and diminished infarct sizes. This polyphenol nanoengineered biohybrid system represents a general and potent platform for the efficient treatment of cardiovascular disorders., (© 2024 Wiley‐VCH GmbH.)

The development of novel therapeutics in the field of spinal neurosurgery faces a litany of translational challenges. Achieving precise drug targeting within the confined spaces associated with the spinal cord, canal and vertebra requires the development of next generation delivery systems and devices. These must be capable of overcoming inherent barriers related to drug diffusion, whilst concurrently ensuring optimal drug distribution and retention. In this review, we provide an overview of the most recent advances in the therapeutic management of diseases and disorders affecting the spine, including systems and devices capable of releasing small molecules and biopharmaceuticals that help eliminate pain and restore the mechanical function and stability of the spine. We highlight material-based approaches and minimally invasive techniques that can be employed to provide control over drug release kinetics and improve retention. We also seek to explore how the newest advancements in nanotechnology, biomaterials, additive manufacturing technologies and imaging modalities can be employed in this translational pursuit. Finally, we discuss the landscape of clinical trials and recently approved products aimed at overcoming the complexities associated with drug delivery to the spine., Competing Interests: Declaration of competing interest The authors declare no competing interests. J.D.B. has an equity position in Treovir inc. and upFront diagnostics. J.D.B. is also a cofounder of centile Bioscience and is on the neuroX1 and QV Bioelectronics scientific advisory boards. G.M.S. is a consultant for Depuy and Johnson and Johnson. G.M.S. also provides research support to NuVasive., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Complex coacervates, formed through electrostatic interactions between oppositely charged polymers, present a versatile platform for drug delivery, providing rapid assembly, selective encapsulation, and responsiveness to environmental stimuli. The architecture and properties of coacervates can be tuned by controlling structural and environmental design factors, which significantly impact the stability and delivery efficiency of the drugs. While environmental design factors such as salt, pH, and temperature play a crucial role in coacervate formation, structural design factors such as polymer concentration, polymer structure, mixing ratio, and chain length serve as the core framework that shapes coacervate architecture. These elements modulate the phase behavior and material properties of coacervates, allowing for a highly tunable system. In this review, we primarily analyze how these structural design factors contribute to the formation of diverse coacervate architecture, ranging from bulk coacervates to polyion complex micelles, vesicles, and cross-linked gels, though environmental design factors are considered. We then examine the effectiveness of these architectures in enhancing the delivery and efficacy of drugs across various administration routes, such as noninvasive (e.g., oral and transdermal) and invasive delivery. This review aims to provide foundational insights into the design of advanced drug delivery systems by examining how the origin and chemical structure of polymers influence coacervate architecture, which in turn defines their material properties. We then explore how the architecture can be tailored to optimize drug delivery for specific administration routes. This approach leverages the intrinsic properties derived from the coacervate architecture to enable targeted, controlled, and efficient drug release, ultimately enhancing therapeutic outcomes in precision medicine.