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ObjectivesTo investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming.Materials and methodsAcoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery. The experimental validation was performed using a tissue-mimicking phantom.ResultsThe developed simulation framework allowed for a parametric study with varying numbers of heating spots, sonication durations, and transducer movement times to evaluate the hyperthermia characteristics for mechanical transducer movement and sector-vortex beamforming. Hyperthermic patterns involving 2-4 sequential focal spots were analyzed. To demonstrate the feasibility of volumetric hyperthermia in the system, a tissue-mimicking phantom was sonicated with two distinct spots through mechanical transducer movement and sector-vortex beamforming. During hyperthermia, the average values of Tmax, T10, Tavg, T90, and Tmin over 200 s were measured within a circular ROI with a diameter of 10 pixels. These values were found to be 8.6, 7.9, 6.6, 5.2, and 4.5 °C, respectively, compared to the baseline temperature.ConclusionsThis study demonstrated the volumetric hyperthermia capabilities of the ExAblate Body system. The simulation framework developed in this study allowed for the evaluation of hyperthermia characteristics that could be implemented with the ExAblate MRgFUS system.

Since extracellular vesicles (EVs) have emerged as a promising drug delivery system, diverse methods have been used to load them with active pharmaceutical ingredients (API) in preclinical and clinical studies. However, there is yet to be an engineered EV formulation approved for human use, a barrier driven in part by the intrinsic heterogeneity of EVs. API loading is rarely assessed in the context of single vesicle measurements of physicochemical properties but is likely administered in a heterogeneous fashion to the detriment of a consistent product. Here, we applied a suite of single-particle resolution methods to determine the loading of rhodamine 6G (R6G) surrogate cargo mimicking hydrophilic small molecule drugs across four common API loading methods: sonication, electroporation, freeze-thaw cycling and passive incubation. Loading efficiencies and alterations in the physical properties of EVs were assessed, as well as co-localization with common EV-associated tetraspanins (i.e., CD63, CD81 and CD9) for insight into EV subpopulations. Sonication had the highest loading efficiency, yet significantly decreased particle yield, while electroporation led to the greatest number of loaded API particles, albeit at a lower efficiency. Moreover, results were often inconsistent between repeated runs within a given method, demonstrating the difficulty in developing a rigorous loading method that consistently loaded EVs across their heterogeneous subpopulations. This work highlights the significance of how chosen quantification metrics can impact apparent conclusions and the importance of single-particle characterization of EV loading.

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Clinical drug administration aims to deliver drugs efficiently and safely to target tissues, organs, and cells, with the objective of enabling their therapeutic effects. Currently, the main approach to enhance a drugs effectiveness is ensuring its efficient delivery to the intended site. Due to the fact that there are still various drawbacks of traditional drug delivery methods, such as high toxicity and side effects, insufficient drug specificity, poor targeting, and poor pharmacokinetic performance, nanocarriers have emerged as a promising alternative. Nanocarriers possess significant advantages in drug delivery due to their size tunability and surface modifiability. Moreover, nano-drug delivery systems have demonstrated strong potential in terms of prolonging drug circulation time, improving bioavailability, increasing drug retention at the tumor site, decreasing drug resistance, as well as reducing the undesirable side effects of anticancer drugs. Numerous studies have focused on utilizing polysaccharides as nanodelivery carriers, developing delivery systems based on polysaccharides, or exploiting polysaccharides as tumor-targeting ligands to enhance the precision of nanoparticle delivery. These types of investigations have become commonplace in the academic literature. This review aims to elucidate the preparation methods and principles of polysaccharide gold nanocarriers. It also provides an overview of the factors that affect the loading of polysaccharide gold nanocarriers with different kinds of drugs. Additionally, it outlines the strategies employed by polysaccharide gold nanocarriers to improve the delivery efficiency of various drugs. The objective is to provide a reference for further development of research on polysaccharide gold nanodelivery systems.

Chemical pesticide delivery is a fundamental aspect of agriculture. However, the extensive use of pesticides severely endangers the ecosystem because they accumulate on crops, in soil, as well as in drinking and groundwater. New frontiers in nano-engineering have opened the door for precision agriculture. We introduced Tobacco mild green mosaic virus (TMGMV) as a viable delivery platform with a high aspect ratio and favorable soil mobility. In this work, we assess the use of TMGMV as a chemical nanocarrier for agriculturally relevant cargo. While plant viruses are usually portrayed as rigid/solid structures, these are "dynamic materials," and they "breathe" in solution in response to careful adjustment of pH or bathing media [e.g., addition of solvent such as dimethyl sulfoxide (DMSO)]. Through this process, coat proteins (CPs) partially dissociate leading to swelling of the nucleoprotein complexes-allowing for the infusion of active ingredients (AI), such as pesticides [e.g., fluopyram (FLP), clothianidin (CTD), rifampicin (RIF), and ivermectin (IVM)] into the macromolecular structure. We developed a "breathing" method that facilitates inter-coat protein cargo loading, resulting in up to  ~ 1000 AIs per virion. This is of significance since in the agricultural setting, there is a need to develop nanoparticle delivery strategies where the AI is not chemically altered, consequently avoiding the need for regulatory and registration processes of new compounds. This work highlights the potential of TMGMV as a pesticide nanocarrier in precision farming applications; the developed methods likely would be applicable to other protein-based nanoparticle systems.

Gastric cancer (GC) is the fifth most common cancer worldwide, particularly prevalent in Asia, especially in China, where both its incidence and mortality rates are significantly high. Meanwhile, nanotechnology has demonstrated great potential in the treatment of GC. In particular, nanodrug delivery systems have improved therapeutic efficacy and targeting through various functional modifications, such as targeting peptides, tumor microenvironment responsiveness, and instrument-based methods. For instance, silica (SiO2) has excellent biocompatibility and can be used as a drug carrier, with its porous structure enhancing drug loading capacity. Polymer nanoparticles regulate drug release rates and mechanisms by altering material composition and preparation methods. Lipid nanoparticles efficiently encapsulate hydrophilic drugs and promote cellular uptake, while carbon-based nanoparticles can be used in biosensors and drug delivery. Targets such as integrins, HER2 receptors, and the tumor microenvironment have been used to improve drug efficacy in GC treatment. Nanodrug delivery techniques not only enhance drug efficacy and delivery capabilities but also selectively target tumor cells. Currently, there is a lack of systematic summarization and synthesis regarding the relationship between nanodrug delivery systems and GC treatment, which to some extent hinders researchers and clinicians from efficiently searching for and referencing related studies, thereby reducing work efficiency. This study aims to systematically summarize the existing research on the relationship between nanodrug delivery systems and GC treatment, making it easier for professionals to search and reference, and thereby promoting further research on the role of nanodrug delivery systems and their clinical applications in GC. This review discusses the applications of functionalized nanocarriers in the treatment of GC in recent years, including surface modifications with targeted markers, the combination of phototherapy, chemotherapy, and immunotherapy, along with their advantages and challenges. It also examines the future prospects of targeted nanomaterials in GC treatment. The review particularly focuses on the combined application of nanocarriers in multiple treatment modalities, such as phototherapy, chemotherapy, and immunotherapy, demonstrating their potential in multimodal treatments. Furthermore, it thoroughly explores the specific challenges that nanocarriers face in GC treatment, such as biocompatibility, drug release control, and clinical translation issues, while providing a systematic outlook on future developments. Additionally, this study emphasizes the potential value and feasibility of nanocarriers in clinical applications, contrasting with most reviews that focus on basic research. Through these innovations, we offer new perspectives and directions for the development of nanotechnology in the treatment of GC. [ABSTRACT FROM AUTHOR]

Development of smart drug delivery systems (DDSs) for effective delivering drugs to targeted areas and achieving controlled drug release (CDR) is critical for cancer chemotherapy. The purpose of this study is synthesis of polydopamine (PDA) nanocapsules and analyze the adsorption and release properties of doxorubicin (DOX). PDA nanocapsules are manufactured using hard template approach. The influence of various parameters such as pH, adsorption time, and initial DOX content on the adsorption and release process is investigated. The resulting adsorption isotherm is consistent with the Langmuir isotherm, indicating that DOX adsorption on PDA nanocapsules is homogenous, uniform, and monolayer. PDA nanocapsules have an adsorption capacity of 689.6 mg g−1 under alkaline conditions, which is attributed to phenol group deprotonation mechanism and electrostatic repulsion. The adsorption kinetics are more consistent with the pseudo‐second‐order model. Furthermore, raising initial concentration of DOX results in a greatly increased adsorption capacity due to a larger driving force. Among the several parameters that can influence the pace and degree of DOX loading and release, local pH is regarded as a significant environmental component in the processes. Thus, pH‐responsive PDA nanocapsules have a significant potential for usage in locations with aberrant pH level, such as cancer tissue. [ABSTRACT FROM AUTHOR]

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‐Ubi29–41. 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. [ABSTRACT FROM AUTHOR]

Chitosan nanoparticles (ChNP) represent an interesting technological platform for drug delivery to the skin due to their mucoadhesive, nontoxic, and biodegradable characteristics, offering advantages in bypassing the stratum corneum and improving drug delivery in dermal administration. This systematic review analyzed the in vivo applicability of ChNP as a substance delivery system to the skin. A literature search was conducted in the databases PubMed, SciELO, and Lilacs using the keywords "nanoparticle," "chitosan," and "skin." Inclusion criteria involved in vivo studies investigating the effects of topical use of these nanoparticles, published between 2013 and 2023, and comparing the nanoparticulate formulation with the free drug. The prevalence of studies conducted on animal models was 94.1%, while only 5.9% were performed on humans. The results suggest that ChNP formulations improved the delivery of therapeutic agents and demonstrated superior efficacy compared to formulations containing the free drug; they exhibited good permeability and tolerability, gradual release of the active molecule, and faster results with minimal adverse effects. Therefore, ChNP containing active substances for topical application emerges as a safe and effective platform with significant potential for drug delivery to the skin, opening new perspectives for their use in innovative formulations. [ABSTRACT FROM AUTHOR]

The development of safe and efficient delivery systems for targeted and controlled release of therapeutic agents has become a major focus in pharmacotherapy. The colon is one organ that serves as an optimal site for the absorption of protein and peptide drugs, offering significant potential for both localized and systemic therapies. However, effective drug delivery is challenged by the need to protect these drugs from premature absorption and maintain their stability across the varying pH levels of the gastrointestinal tract. In this study, we introduce, for the first time, a fully natural hydrogel system composed of N-acetylated chitosan and alginate, crosslinked using a phenylalanine-phenylalanine dipeptide. The hydrogel demonstrates a unique swelling behavior, allowing for a solvent-free drug-loading method and pH-sensitive release properties. In a colon-simulated pH environment, the hydrogel achieved a high drug release efficiency, with 77.6% of the tested drug sulfasalazine and 51% of hydrocortisone over 5 hours. These findings underscore hydrogel's potential as a promising drug delivery carrier for targeted gastrointestinal treatments, with the capacity to enhance the efficacy of current therapeutic options. [ABSTRACT FROM AUTHOR]

Poly(N‐isopropylacrylamide) (PNIPAM) is a versatile polymer known for its phase transition properties, exhibiting a lower critical solution temperature (LCST) of approximately 32°C. Below this temperature, PNIPAM is hydrophilic, while above it, the polymer becomes hydrophobic, making it ideal for thermosensitive drug delivery systems (DDSs). In tissue engineering, PNIPAM provides a biocompatible, nontoxic and stimuli‐responsive surface for cell culture. Its nontoxic nature ensures safety in medical applications. PNIPAM enhances biosensing diagnostics through its affinity for biomolecules, improving accuracy. Widely used in hydrogels, smart textiles, soft robotics and various medical applications, PNIPAM adapts to environmental changes. Its straightforward synthesis allows for the creation of diverse copolymers and composites, applicable in selective reactions and conjugations with fluorescent tags or chemical modifications. PNIPAM's versatility extends to pH‐responsive alternatives, broadening its application spectrum. Practical examples include phase separation in water treatment and cleaning processes. This discussion explores PNIPAM's biomedical and drug delivery applications, particularly in cancer treatment, photothermal therapy (PTT) and photodynamic therapy (PDT), gene delivery and medical imaging. Additionally, it highlights PNIPAM's noncancerous applications, such as small interfering RNA (siRNA) targeting of oncogenes and detailed imaging of deep and tumour tissues. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION 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 (Ca2+), and garlic protein hydrolysates (GPH), and to develop hydrogel beads for targeted delivery of bioactive constituents to the gastrointestinal tract.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.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. [ABSTRACT FROM AUTHOR]

This research investigates the rheological behavior of the Poloxamer–chitosan thermogel system for the release of doxorubicin, which is a chemotherapy agent. To design the experiment, the response surface method was used to optimize the formula and investigate the mutual effects of the variables on the rheological properties of the system. In this experimental design, Poloxamer as a thermogel matrix (15–20%) and chitosan biopolymer as an additive (0.1–0.3%) were used and the pH of the test environment was determined in the range of 2.0–7.5. The results showed that the rheological behavior of the Poloxamer–chitosan combination has the best fit according to the Herschel–Bulkley model with a correlation coefficient of 100%. Also, adding chitosan to Poloxamer decreased the gelation temperature and gelation time. The results showed that the concentration of Poloxamer and chitosan as well as system temperature have a significant effect on the rheological behavior of thermogel. The optimized formula showed favorable rheological properties including high viscosity and appropriate degradation rate. The study showed the sustained release of the drug in the in vitro environment of the thermogel system during 144 h. The kinetics of the drug's release were also studied based on zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. It was found that the Higuchi (R2 = 0.9888) and Korsmeyer–Peppas (R2 = 0.9851) models are the best models for the prediction of release kinetics of doxorubicin. Therefore, the design of the Poloxamer–chitosan thermogel system has the potential to be used as an in situ drug delivery system for doxorubicin. [ABSTRACT FROM AUTHOR]

Bioceramics composed of calcium and magnesium silicates have garnered increasing attention for the development of porous scaffolds in bone tissue engineering (BTE). This heightened interest is primarily attributed to their remarkable bioactivity and their capacity to form strong bonds with hard tissue. Fabricating nanocomposite scaffolds is a recognized approach for improving the characteristics of scaffolds used in BTE. This research investigates the mechanical and biological properties, antibacterial activity, and drug-release characteristics of scaffolds composed of akermanite (AKT), monticellite (MON), and monticellite-akermanite (MON-AKT). These scaffolds were fabricated utilizing the space holder process. Additionally, the in vitro drug release profile and antimicrobial activity of Azithromycin (AZT)-loaded MON-AKT composite scaffolds were investigated. The findings showed that the Mon-15 wt% AKT nanocomposite scaffold had the highest density, the smallest grain and micropore sizes, and the lowest porosity. In contrast, integrating AKT into MON-based composite scaffolds resulted in materials characterized by high mechanical strength and stability within physiological environments. The MON-AKT nanocomposite scaffolds exhibited cytocompatibility and demonstrated a high level of alkaline phosphatase (ALP) activity in osteogenic studies. Furthermore, antimicrobial activity assessments revealed that the AZT-encapsulated MON-AKT composite scaffolds effectively inhibited the growth of both S. aureus and E. coli bacteria. The outcomes showed that the antibacterial efficacy of the scaffold depends on both the amount of AZT and the type of bacteria. Overall, MON-AKT/3AZT scaffolds exhibited significantly superior bacterial inhibition compared to other scaffolds, making it a promising option for treating bone tissue defects. [ABSTRACT FROM AUTHOR]

Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, a bioengineering platform for efficient mRNA loading and functional delivery using bionormal nanoparticles, extracellular vesicles (EVs), is established by expressing a highly specific RNA‐binding domain fused to CD63 in EV producer cells stably expressing the target mRNA. The additional combination with a fusogenic endosomal escape moiety, Vesicular Stomatitis Virus Glycoprotein, enables functional mRNA delivery in vivo at doses substantially lower than currently used clinically with synthetic lipid‐based nanoparticles. Importantly, the application of EVs loaded with effective cancer immunotherapy proves highly effective in an aggressive melanoma mouse model. This technology addresses substantial drawbacks currently associated with EV‐based nucleic acid delivery systems and is a leap forward to clinical EV applications. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion injury (MI/RI) generates reactive oxygen species (ROS) and initiates inflammatory responses. Traditional therapies targeting specific cytokines or ROS often prove inadequate. An innovative drug delivery system (DDS) is developed using neutrophil decoys (NDs) that encapsulate 18β‐glycyrrhetinic acid (GA) within a hydrolyzable oxalate polymer (HOP) and neutrophil membrane vesicles (NMVs). These NDs are responsive to hydrogen peroxide (H2O2), enabling controlled GA release. Additionally, NDs adsorb inflammatory factors, thereby reducing inflammation. They exhibit enhanced adhesion to inflamed endothelial cells (ECs) and improved penetration. Once internalized by cardiomyocytes through clathrin‐mediated endocytosis, NDs protect against ROS‐induced damage and inhibit HMGB1 translocation. In vivo studies show that NDs preferentially accumulate in injured myocardium, reducing infarct size, mitigating adverse remodeling, and enhancing cardiac function, all while maintaining favorable biosafety profiles. This neutrophil‐based system offers a promising targeted therapy for MI/RI by addressing both inflammation and ROS, holding potential for future clinical applications. [ABSTRACT FROM AUTHOR]

Peptide coacervates self‐assembling via liquid‐liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non‐cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross the cellular membranes remain unknown. Here, using multimodal imaging, data analytics, and biochemical inhibition assays, we identify the key steps by which droplets enter the cell. We find that the uptake follows a non‐canonical pathway and instead integrates essential features of macropinocytosis and phagocytosis, namely active remodeling of the actin cytoskeleton and appearance of filopodia‐like protrusions. Experiments using giant unilamellar vesicles show that the coacervates attach to the bounding membrane in a charge‐ and cholesterol‐dependent manner but do not breach the lipid bilayer barrier. Cell uptake in the presence of small molecule inhibitors – interfering with actin and tubulin polymerization – confirm the active role of cytoskeleton remodeling, most prominently evident in electron microscopy imaging. These findings suggest a peculiar internalization mechanism for viscoelastic, glassy coacervate droplets combining features of non‐specific uptake of fluids by macropinocytosis and particulate uptake of phagocytosis. The broad implications of this study will enable to enhance the efficacy and utility of coacervate‐based strategies for intracellular delivery of macromolecular therapeutics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nasopharyngeal cancer (NPC) is a challenging malignancy with a poor prognosis due to late diagnosis and resistance to conventional treatments. Nanotechnology offers promising solutions to address these limitations by enabling targeted drug delivery, enhancing therapeutic efficacy, and facilitating multimodal treatment strategies. By leveraging the unique properties of nanomaterials and nanocarrier systems, innovative approaches for early detection, targeted treatment, and multimodal therapy can be developed, paving the way for more effective and personalized management of NPC. This review provides a comprehensive overview of recent developments and applications of nanotechnology in NPC therapy, focusing on improving drug stability, biodistribution, and targeted delivery to NPC tumors. [ABSTRACT FROM AUTHOR]

[Display omitted] • Comprehensive analysis of novel treatment modalities for Glioblastoma (GBM). • Role of nanocarriers in addressing limitations with conventional GBM therapeutics. • Updates of clinical landscape of novel GBM therapeutics. • Limitations with novel nanoparticles approach in GBM therapeutics. 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. [ABSTRACT FROM AUTHOR]

Aim: The study aims to improve glioblastoma multiforme (GBM) treatment by combining temozolomide (TMZ) and quercetin (Qct), using folic acid (FA)-conjugated exosomes to overcome TMZ resistance and enhance blood–brain barrier (BBB) penetration. Methods: Exosomes were isolated and after characterizing and modifying their surfaces with FA, drug loading of TMZ and Qct into exosomes was done. In vitro assays, including cell viability tests, RT-PCR, Western-blotting and flow-cytometry, were performed using U87MG and U251MG GBM cell lines. In vivo analysis included administering exosome-drug formulations to glioblastoma-bearing Wistar rats, monitored through optical imaging and PET scans, followed by post-mortem immunohistochemistry and histological examination. Results: The results showed successful exosome isolation and FA conjugation, with drug release studies indicating accelerated release of TMZ and Qct in acidic conditions, enhancing cytotoxicity. Immunofluorescence indicated greater exosome uptake in GBM cells due to FA conjugation. Cell viability assays demonstrated increased toxicity of the combination therapy, correlating with elevated apoptosis. In vivo studies revealed significant tumor size reduction, alongside increased apoptosis and reduced angiogenesis, particularly in the TMZ-Qct-Exo-FA group. Conclusion: FA-conjugated exosomes loaded with TMZ and Qct represent a promising strategy to enhance GBM treatment efficacy by improving drug delivery, apoptosis induction and inhibiting the PI3K/Akt/mTOR pathway. Graphical Abstract Schematic illustration of exosome isolation and conjugation followed by loading with temozolomide (TMZ) and Quercetin (Qct) for glioblastoma therapy. (A) Process of isolating exosomes and conjugating them with folic acid loaded with TMZ and Qct (B) Function of exosomes conjugated with folic acid in a rat model of glioblastoma (C) Mechanism of how exosomes bearing TMZ and Qct work inside the glioblastoma cell line. Article highlights The study emphasizes the successful use of exosome encapsulation to enhance the delivery of temozolomide (TMZ) and quercetin (Qct) across the blood–brain barrier (BBB), improving drug stability for glioblastoma multiforme (GBM) therapy. Encapsulating TMZ and Qct within exosomes (TMZ-Qct-Exo) showed significantly greater potential in reducing GBM cell viability compared with their unencapsulated counterparts, suggesting an effective approach against TMZ resistance. The introduction of folic acid-conjugated exosomes (TMZ-Qct-Exo-FA) enhanced the targeting of GBM cells, leading to better cellular uptake and improved therapeutic outcomes marked by greater apoptosis and increased caspase-3 levels. The combined treatment effectively inhibited the PI3K/Akt/mTOR signaling pathway, vital for tumor growth and survival, thereby boosting the anti-tumor effects of the TMZ-Qct-Exo-FA treatment. In vivo studies demonstrated that the TMZ-Qct-Exo-FA formulation resulted in superior tumor targeting, significantly reduced tumor size and higher levels of apoptotic markers compared with alternative treatment methods. The findings highlight that exosome-mediated drug delivery could serve as a promising strategy to circumvent resistance mechanisms commonly associated with TMZ in GBM treatment. The research indicates that combining exosome technology with conventional chemotherapy could pave the way for new therapeutic modalities in the treatment of aggressive brain tumors like GBM. The use of folic acid as a targeting moiety suggests an innovative approach to enhance specificity in drug delivery systems directed at tumor cells. These results underscore the need for further clinical studies to explore the full potential of exosome-mediated delivery systems in enhancing the effectiveness of existing cancer therapies. [ABSTRACT FROM AUTHOR]

The type of algorithm employed to predict drug release from liposomes plays an important role in affecting the accuracy. In recent years, Machine Learning (ML) has shown potential for modeling complex drug delivery systems and predicting drug release dynamics with a greater degree of precision. In this regard, Random Forest (RF) and Support Vector Machine (SVM) are two ML algorithms that have been extensively applied in various biomedical and drug delivery contexts. Yet, direct comparisons of their predictive accuracy in modeling ultrasound-triggered drug release from liposomes remain limited. Existing studies predominantly focus on drug release under static conditions or with limited external stimuli rather than the dynamic, nonlinear responses observed under ultrasound exposure. Objective: This study presents a comparative analysis of RF and SVM for predicting calcein release from ultrasound-triggered, targeted liposomes under varied low-frequency ultrasound (LFUS) power densities (6.2, 9, and 10 mW/cm2). Methods: Liposomes loaded with calcein and targeted with seven different moieties (cRGD, estrone, folate, Herceptin, hyaluronic acid, lactobionic acid, and transferrin) were synthesized using the thin-film hydration method. The liposomes were characterized using Dynamic Light Scattering and Bicinchoninic Acid assays. Extensive data collection and preprocessing were performed. RF and SVM models were trained and evaluated using mean absolute error (MAE), mean squared error (MSE), coefficient of determination (R²), and the a20 index as performance metrics. Results: RF consistently outperformed SVM, achieving R2 scores above 0.96 across all power densities, particularly excelling at higher power densities and indicating a strong correlation with the actual data. Conclusion: RF outperforms SVM in drug release prediction, though both show strengths and apply based on specific prediction needs. [ABSTRACT FROM AUTHOR]

Small soft robotic systems are being explored for myriad applications in medicine. Specifically, magnetically actuated microrobots capable of remote manipulation hold significant potential for the targeted delivery of therapeutics and biologicals. Much of previous efforts on microrobotics have been dedicated to locomotion in aqueous environments and hard surfaces. However, our human bodies are made of dense biological tissues, requiring researchers to develop new microrobotics that can locomote atop tissue surfaces. Tumbling microrobots are a sub-category of these devices capable of walking on surfaces guided by rotating magnetic fields. Using microrobots to deliver payloads to specific regions of sensitive tissues is a primary goal of medical microrobots. Central nervous system (CNS) tissues are a prime candidate given their delicate structure and highly region-specific function. Here we demonstrate surface walking of soft alginate capsules capable of moving on top of a rat cortex and mouse spinal cord ex vivo , demonstrating multi-location small molecule delivery to up to six different locations on each type of tissue with high spatial specificity. The softness of alginate gel prevents injuries that may arise from friction with CNS tissues during millirobot locomotion. Development of this technology may be useful in clinical and preclinical applications such as drug delivery, neural stimulation, and diagnostic imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AbstractThe biomedical industry has witnessed a transformative evolution with the advent of 3D printing technology. However, inherent limitations, such as the inability to produce dynamic human tissues due to the absence of the temporal dimension, have persisted, resulting in static and inanimate printed products. To address this challenge and enable the creation of dynamic and living constructs, the concept of 4D printing has emerged, marking a paradigm shift in additive manufacturing. In 4D printing, time becomes the fourth dimension, breathing life into previously static creations. This review paper explores the journey from 3D to 4D printing and the pivotal role of time in the additive manufacturing process. Specifically, it highlights the integration of time-dependent responsive materials, focusing on stimuli-responsive hydrogels, as a cornerstone in 4D printing advancements. These materials exhibit a remarkable ability to adapt and respond to various stimuli, encompassing physical, chemical, and biological signals. The review delves into recent publications on the synergy between these stimuli and responsive materials, shedding light on their intricate interactions and potential applications. One of the primary areas of interest lies in medical applications, notably tissue engineering, where 4D printing holds immense promise. The paper explores the utilization of 4D printing in creating biomimetic scaffolds that can dynamically adapt to complex tissue environments. Furthermore, the review discusses the technical considerations and prospects of 4D printing technology, emphasizing its potential to revolutionize the biomedical landscape. The amalgamation of 4D printing and stimuli-responsive materials opens new avenues for personalized medicine, localized drug delivery, and regenerative therapies, bridging the gap between static 3D printing and the dynamic requirements of modern healthcare. The present review offers a complete examination of the evolution, challenges, and prospects of 4D printing in biomedical applications, paving the way for transformative innovations in the field. [ABSTRACT FROM AUTHOR]

This article explores the multifaceted potential of pullulan‐based films across food‐packaging, pharmaceutical, biomedical, and cosmetic applications. In food‐packaging, pullulan films serve as transparent, flexible, and high‐oxygen barrier materials, effectively preserving the freshness and quality of a wide range of fruits and vegetables. Edible pullulan films extend the shelf life and enhance food safety, while active pullulan films inhibit microbial growth and oxidation, thus supports food preservation. In the pharmaceutical industry, pullulan‐based films offer promising solutions for oral drug delivery, providing biodegradable and rapid disintegration for enhanced solubility and bioavailability of drugs. Additionally, due to their mechanical strength, biocompatibility, and antimicrobial properties, pullulan films demonstrate potential in wound dressings and tissue engineering applications. Furthermore, pullulan's utility extends to the cosmetic industry, where it is used widely in various ingredients in skincare products, cosmetics, and personal care items. Its moisturizing, stabilizing, and film‐forming properties make pullulan an attractive component in the industry. Future research directions should focus on cost‐effective production methods and expanding industrial applications to further enhance their effectiveness and versatility. This in‐depth analysis highlights the significant potential of pullulan‐based films across multiple industries and underscores the importance of continued research and development efforts to fully unlock their diverse applications and benefits. [ABSTRACT FROM AUTHOR]

Miniature soft robots designed with magnetoelastic materials have the potential for noninvasive navigation in narrow spaces and innovative clinical therapies. However, the complex environment inside the body imposes stringent requirements on the motility and environmental adaptability of robots. Inspired by carangiform fish morphology and kinematics, a 3D free‐swimming magnetic milliswimmer with enhanced controllability, maneuverability, and environmental adaptability is developed. This milliswimmer is negatively buoyant like most fishes and employs magnetic torque to actuate its body. It mimics fish muscle contractions and generates a carangiform‐like body curvature distribution that results in comparable swimming behavior and performance. Compared with previous designs, it achieves over six times the equivalent motion performance and enables gravity‐resisting free‐swimming, with fish‐like maneuverability (a minimum turning radius of just 0.05 body length and a maximum turning rate of up to 4737 deg s−1). Its ability to transport and release cargo precisely while navigating three‐dimensionally in an ex vivo porcine urinary system is demonstrated. The designed bionic magnetic soft robot is expected to advance biomedical applications of magnetoelastic materials, particularly in urinary and other clinical treatments. [ABSTRACT FROM AUTHOR]

High dose-rate brachytherapy presents a promising therapeutic avenue for prostate cancer management, involving the temporary implantation of catheters which deliver radioactive sources to the cancerous site. However, as catheters puncture and penetrate the prostate, tissue deformation is evident which may affect the accuracy and efficiency of the treatment. In this work, a data-driven in silico modelling procedure is proposed to simulate brachytherapy while accounting for prostate biomechanics. Comprehensive magnetic resonance and transrectal ultrasound images acquired prior, during and post brachytherapy are employed for model personalisation, while the therapeutic procedure is simulated via sequential insertion of multiple catheters in the prostate gland. The medical imaging data are also employed for model evaluation, thus, demonstrating the potential of the proposed in silico procedure to be utilised pre- and intra-operatively in the clinical setting. [ABSTRACT FROM AUTHOR]

Trimethyl lock (TML) systems have become increasingly important in medicinal and bioorganic chemistry, particularly for their roles in the targeted delivery of therapeutic agents and as integral components in fluorogenic probes for cellular imaging. The simplicity and efficiency of their synthesis have established TML systems as versatile platforms for the controlled release of active molecules under particular physiological conditions. This review consolidates recent advancements in the application of TML systems, with a focus on their use in drug delivery, cellular imaging, and other areas where precise molecular release is crucial. Additionally, we discuss the synthetic strategies employed to construct TML‐based conjugates, underscoring their potential to enhance the specificity and efficacy of bioactive compounds in various biomedical applications. [ABSTRACT FROM AUTHOR]

Orthopedic implants have faced challenges in treating bone defects due to various factors, including inadequate osseointegration, oxidative stress, bacterial infection, immunological rejection, and poor individualized treatment. These challenges profoundly affect both the results of treatment and patients' daily lives. There is great promise for the layer-by-layer (LbL) assembly method in tissue engineering. The method primarily relies on electrostatic attraction and entails the consecutive deposition of electrolyte complexes with opposite charges onto a substrate, leading to the formation of homogeneous single layers that can be quickly deposited to produce nanolayer films. LbL has attracted considerable interest as a coating technology because of its ease of production, cost-effectiveness, and capability to apply diverse biomaterial coatings without compromising the primary bio-functional properties of the substrate materials. This review will look into the fundamentals and evolution of LbL in orthopedics, provide an analysis of the chemical strategy used to prepare bone implants with LbL and introduce the application of LbL bone implants in orthopedics over recent years. Among the many potential uses of LbL, such as the implementation of sustained-release and programmed drug delivery, which in turn promotes the osseointegration and the development of new blood vessels, as well as antibacterial, antioxidant, and other similar applications. In addition, we offer a thorough examination of cell behavior and biomaterial interaction to facilitate the advancement of next-generation LbL films for tissue engineering. [ABSTRACT FROM AUTHOR]

The field of drug delivery has significantly advanced tumor therapy, yet challenges such as the predictability of treatment outcomes and the real‐time monitoring of tumor progression, such as recurrence or metastasis. Luminescent metal–organic frameworks (L‐MOFs) are a promising solution to overcome these issues. This review offers a comprehensive exploration of the design and synthesis of L‐MOFs, presenting their crucial optical properties. The review highlights the pivotal role of L‐MOFs in enabling precision medicine for tumor treatment driven by their performance. Through strategically harnessing light‐manipulated metal–organic frameworks (MOFs), real‐time therapeutic monitoring and precise spatiotemporal control in tumor treatment can be achieved. Moreover, this review meticulously examines the influence of photomanipulating MOFs on in situ drug synthesis, introducing the catalytic role in light‐manipulated gas therapy. Additionally, the role of L‐MOFs as gene therapy vectors that utilize light to trigger gene expression responses is also comprehensively explored in the article, aiming to highlight their role in enabling tumor therapy through gene therapy. The review concludes by proposing an artificial intelligence (AI)‐mediated blueprint for tumor treatment with L‐MOFs, aiming to pave the way for innovative approaches through light manipulation. [ABSTRACT FROM AUTHOR]

Mucus is a hydrated, viscoelastic, and adhesive gel that lubricates and protects the body from pathogens; however, its protective function hinders drug/nanomedicine diffusion and treatment efficiency. Therefore, novel drug delivery strategies are required to overcome challenging mucosal barriers. Here, multi‐responsive nanogels (NGs) are developed and explored their interaction with mucus. Specific NG features (e.g., surface charge, temperature responsiveness, and redox response) are evaluated in a typical mucus‐associated environment (i.e., mucin proteins and high glutathione concentrations). The results demonstrate that biocompatibility and the capacity to deliver a protein through mucosal barriers in different in vitro and in vivo models highlight the importance of specific NG design elements. Disulfide bonds are highlighted as redox‐sensitive cross‐linkers within the NG structure as critical for drug delivery performance; they function as degradation points that enable NG degradation and subsequent drug release and anchoring points to adhere to mucin, thereby enhancing their residence time at the desired site of action. Additionally, it is confirmed that surface charges impact interactions with mucin; positively charged NGs exhibit improved interactions with mucin compared to negatively charged and neutral NGs. Overall, the findings underline the importance of redox response and surface charge in NG design for reaching efficient mucosal drug delivery. [ABSTRACT FROM AUTHOR]

Materials data science and machine learning (ML) are pivotal in advancing cancer treatment strategies beyond traditional methods like chemotherapy. Nanotherapeutics, which merge nanotechnology with targeted drug delivery, exemplify this advancement by offering improved precision and reduced side effects in cancer therapy. The development of these nanotherapeutic agents depends critically on understanding nanoparticle (NP) properties and their biological interactions, often analyzed through molecular dynamics (MD) simulations. This study enhances these analyses by integrating ML with MD simulations, significantly improving both prediction accuracy and computational efficiency. We introduce a comprehensive three-stage methodology for predicting the solvent-accessible surface area (SASA) of NPs, which is crucial for their therapeutic efficacy. The process involves training an ML model to forecast the many-body tensor representation (MBTR) for future time steps, applying data augmentation to increase dataset realism, and refining the SASA predictor with both augmented and original data. Results demonstrate that our methodology can predict SASA values 299 time steps ahead with a 40-fold speed improvement and a 25% accuracy increase over existing methods. Importantly, it provides a 300-fold increase in computational speed compared to traditional simulation techniques, offering substantial cost and time savings for nanotherapeutic research and development. [ABSTRACT FROM AUTHOR]

This study shows that the synthesis of di‐BCP between amino acid l‐glutamic acid (l‐GluA) and hydrophobic polycaprolactone (PCL) leads to multifunctional and multifaceted capsule formation with different dispersion solvents. Successful synthesis of [(l‐GluA)‐b‐(PCL)] was confirmed by using FTIR and 1H NMR characterizations. For morphological studies, synthesized di‐BCP of [(l‐GluA)‐b‐(PCL)] was dispersed in four different solvents such as acetone, DMSO, IPA, and ethanol and was used for sample preparation for SEM imaging. Interestingly, smooth‐surfaced NPs (defined as type I NPs), rough‐surfaced NPs (type II NPs), porous NPs (type III NPs), and football‐type deep excavation having NPs (defined as type IV NPs). Furthermore, these NPs were characterized through BET, AFM, and DLS for particle size and ζ potential of NPs. LC for types III and IV NPs was calculated to be 1.96% ± 0.01% and 1.92% ± 0.01%, respectively. EE of types III and IV NPs was calculated to be 91% ± 1.5% and 94% ± 1.2%. We used K562 (leukemia blood cancer) and HEK293 (embryonic kidney) cells for in vitro studies. DOX@[(l‐GluA)‐b‐(PCL)] nanoformulation related to types III and IV NPs shows significant early apoptosis that is, 29.17%, which is a remarkable programmed cell death for these porous nanoparticles. [ABSTRACT FROM AUTHOR]

The presence of E‐cadherin⋯E‐cadherin interactions in the intercellular space (paracellular pathway) poses a notable limitation in drug delivery across the blood‐brain barrier (BBB). ADTC5 peptide has shown promising results in improving drug delivery across the BBB by modulating E‐cadherin⋯E‐cadherin interactions. However, the study of E‐cadherin⋯ADTC5 amino acid interactions using quantum mechanics approach has not been observed clearly. Herein, we observed the interaction between E‐cadherin⋯ADTC5 amino acids using density functional theory (DFT). Natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM), and reduced density gradient (RDG) analysis are performed to study the non‐covalent interaction in detail. The Arg55⋯Asp2 shows the strongest interaction between E‐cadherin⋯ADTC5 modulation, indicated by the highest stabilization energy (E(2)), and hydrogen bonding energy (EHB) about 22.04 and −6.90 kcal/mol, respectively. This interaction is dominated by hydrogen bonding. Such advancements could lead to significant improvements in therapeutic strategies for neurodegenerative diseases, where effective drug delivery across the BBB remains a major challenge. [ABSTRACT FROM AUTHOR]

The challenge with breast cancer is its ongoing high prevalence and difficulties in early detection and access to effective care. A solution lies in creating tailored metal–organic frameworks to encapsulate anticancer drugs, enabling precise and targeted treatment with less adverse effects and improved effectiveness. Zeolitic imidazolate framework‐8 (ZIF‐8) and carboplatin (CP)‐loaded ZIF‐8 were synthesized and characterized using various analytical techniques. High Resolution‐transmission electron microscopy of ZIF‐8 and CP@ZIF‐8 indicates that the particles had a spherical shape and were nanosized. The drug release rate of CP is 98% under an acidic medium (pH 5.5) because of the dissolution of ZIF‐8 into its coordinating ions, whereas 35% in a physiological medium (pH 7.4) with the addition of CP, the high porosity, and pore diameter of ZIF‐8 decrease from 1243 to 1041 m2/g. Breast cancer MCF‐7 cells were shown greater IC50 in CP@ZIF‐8 (15.01 ± 3.03 µg/mL) than free CP (34.98 ± 4.25 µg/mL) in an in vitro cytotoxicity assessment. The cytotoxicity of the CP@ZIF‐8 against MCF‐7 cells was studied using the methylthiazolyldiphenyl‐tetrazolium bromide method. The morphological changes were examined using fluorescent staining (acridine orange–ethidium bromide and Hoechst 33258) methods. The comet assay assessed the DNA fragmentation (single‐cell gel electrophoresis). The results from the study revealed that CP@ZIF‐8 can be used in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p‐glycoprotein (P‐gp) mediated drug efflux is one of the primary causes, the development of P‐gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P‐gp exists in many tissues, the non‐selective P‐gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P‐gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P‐gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post‐modification, various benzofuran‐fused‐piperidine derivatives were achieved and the biological evaluation identified 16 c with potent P‐gp inhibitory activity. Notably, 16 c was intestine specific and showed almost none absorption (F=0.82 %), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA‐MB‐231 xenograft model, the oral administration of Taxol and 16 c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy. [ABSTRACT FROM AUTHOR]

Nanoparticles are attractive therapeutic tools due to their distinctive characteristics, including more accurate drug delivery, improved bioavailability, and enhanced targeted therapy. This review offers a comprehensive analysis of the therapeutic potentials of cutting-edge nanoparticles as demonstrated in human clinical trials, based on empirical evidence. Through systematic searches of major scientific databases, relevant studies published up to March 2024 were included, focusing on clinical trials utilizing advanced nanoparticles for therapeutic purposes. The review discusses the diverse applications of nanoparticles in oncology, infectious diseases, neurology, and other medical fields. Additionally, it scrutinizes the safety profiles, efficacy outcomes, and challenges associated with nanoparticle-based therapies. The findings underscore significant progress in translating nanoparticle research into clinical practice and highlight the potential of these innovative platforms to revolutionize medical treatments. This review contributes valuable insights into the growing field of nanoparticle-based therapeutics, fostering a deeper understanding of their clinical applications and implications in medical practice. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive prodrugs of anticancer drugs are advantageous for the selective delivery of drugs to cancer cells with minimized off‐target side effects. In the present study, esterase‐activatable fluorogenic prodrugs of the chemotherapeutic drug 5‐fluorouracil (5‐FU) have been rationally designed and synthesized using multi‐step organic synthesis. While 5‐FU was connected directly with the fluorophore via a C−N bond in the prodrug BJ‐50, an additional self‐immolative benzylic spacer with a carbonate linker was incorporated in the prodrug BJ‐92. Although absorption and emission spectroscopic studies revealed the activation of both the prodrugs by porcine liver esterase (PLE), reverse‐phase HPLC studies confirmed the inability of BJ‐50 to release the active drug 5‐FU. In contrast, a sustained release of 5‐FU and Cou‐OH was observed from BJ‐92 in the presence of PLE. The endogenous esterase‐mediated activation of the prodrug BJ‐92 was validated by the turn‐on fluorescence in A549 cells and the anti‐proliferative activities in A549, and HEK‐293 cells. Modulation of the expression of a few cancer marker proteins by BJ‐92 and 5‐FU was studied to evaluate their anticancer activities. As esterases are overexpressed in cancer cells, the prodrug in the present study would be helpful in selectively delivering 5‐FU to cancer cells with reduced off‐target side‐effects. [ABSTRACT FROM AUTHOR]

Despite the availability of a number of efficacious treatments for Parkinson's disease, their limitations and drawbacks, particularly related to low brain bioavailability and associated side effects, emphasize the need for alternative and more effective therapeutic approaches. Nanomedicine, the application of nanotechnology in medicine, has received considerable interest in recent years as a method of effectively delivering potentially therapeutic molecules to the brain. In particular, polymeric nanoparticles, constructed from biodegradable polymer, have shown great promise in enhancing therapeutic efficacy, reducing toxicity, and ensuring targeted delivery. However, their clinical translation remains a considerable challenge. This article reviews recent in vitro and in vivo studies using polymeric nanoparticles as drug and gene delivery systems for Parkinson's disease with their challenges and future directions. We are also particularly interested in the technical properties, mechanism, drugs release patterns, and delivery strategies to overcome the blood–brain barrier. © 2024 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Bone-related disorders create critical-sized bone defects that require multifunctional bone graft materials for successful bone repair. Integration of therapeutics with 3D-printed calcium phosphate (CaP) scaffolds offers a personalized treatment option. The inherent properties of CaP enable it to act as a bone substitute, while drug delivering abilities provide a new dimension through localized drug delivery. It enhances both therapeutic efficacy and patient compliance. Controlled delivery of drugs significantly impacts the process of bone regeneration. It can be achieved through various strategies, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion 3D printing. Understanding drug release mechanisms aids in assessing the in vivo performance of multifunctional scaffolds. 3D printing has revolutionized bone tissue engineering (BTE) by enabling the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration. The superior biocompatibility, customizable bioactivity, and biodegradability have enabled calcium phosphate (CaP) to gain significance as a bone graft material. 3D-printed (3DP) CaP scaffolds allow precise drug delivery due to their porous structure, adaptable structure–property relationship, dynamic chemistry, and controlled dissolution. The effectiveness of conventional scaffold-based drug delivery is hampered by initial burst release and drug loss. This review summarizes different multifunctional drug delivery approaches explored in controlling drug release, including polymer coatings, formulation integration, microporous scaffold design, chemical crosslinking, and direct extrusion printing for BTE applications. The review also outlines perspectives and future challenges in drug delivery research, paving the way for next-generation bone repair methodologies. [ABSTRACT FROM AUTHOR]

Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self‐assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP‐2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP‐2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4+ T cells. Ultimately, DI/Pep1 attenuated tumor‐associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment. [ABSTRACT FROM AUTHOR]

Hydrogels have been used in the clinic since the late 1980s with broad applications in drug delivery, cosmetics, tissue regeneration, among many other areas. The past three decades have witnessed rapid advances in the fields of polymer chemistry, crosslinking approaches, and hydrogel fabrication methods, which have collectively brought many new hydrogel products, either injectable or non‐injectable, to clinical studies. In an article published in 2020 entitled "Hydrogels in the clinic", we reviewed the clinical landscape and translational challenges of injectable hydrogels. Here, we provide an update on the advances in the field and also extend the scope to include non‐injectable hydrogels. We highlight recently approved hydrogel products, provide an update on the clinical trials of injectable hydrogels, and discuss active clinical trials of topically applied and implantable hydrogels. [ABSTRACT FROM AUTHOR]

Antibody‐drug conjugates (ADCs), chemotherapeutic agents conjugated to an antibody to enhance their targeted delivery to tumors, represent a significant advancement in cancer therapy. ADCs combine the precise targeting capabilities of antibodies and the potent cell‐killing effects of chemotherapy, allowing for enhanced cytotoxicity to tumors while minimizing damage to healthy tissues. Here, we provide an overview of the current clinical landscape of ADCs, highlighting 11 U.S. Food and Drug Administration (FDA)‐approved products and discussing over 500 active clinical trials investigating newer ADCs. We also discuss some key challenges associated with the clinical translation of ADCs and highlight emerging strategies to overcome these hurdles. Our discussions will provide useful guidelines for the future development of safer and more effective ADCs for a broader range of indications. [ABSTRACT FROM AUTHOR]

Silica nanoparticles (SNPs) have been extensively studied and used in different dental applications to promote improved physicochemical properties, high substance loading efficiency, in addition to sustained delivery of substances for therapeutic or preventive purposes. Therefore, this study aimed to review the SNPs applications in nanomaterials and nanoformulations in dentistry, discussing their effect on physicochemical properties, biocompatibility and ability to nanocarry bioactive substances. Literature searches were conducted on PubMed, Web of Science, and Scopus databases to identify studies examining the physicochemical and biological properties of dental materials and formulations containing SNPs. Data extraction was performed by one reviewer and verified by another A total of 50 were reviewed. In vitro studies reveal that SNPs improved the general properties of dental materials and formulations, such as microhardness, fracture toughness, flexural strength, elastic modulus and surface roughness, in addition to acting as efficient nanocarriers of substances, such as antimicrobial, osteogenic and remineralizing substances, and showed biocompatibility SNPs are biocompatible, improve properties of dental materials and serve as effective carriers for bioactive substances Overall, SNPs are a promising drug delivery system that can improve dental materials biological and physicochemical and aesthetic properties, increasing their longevity and clinical performance. However, more studies are needed to elucidate SNPs short- and long-term effects in the oral cavity, mainly on in vivo and clinical studies, to prove their effectiveness and safety. • Silica nanoparticles have been widely studied and used in dentistry in intra and extraoral materials and formulations. • In vitro results reveal that silica nanoparticles enhance the physicochemical properties of dental materials. • In vitro results also confirm the potential silica nanoparticles can effectively load and release antimicrobial substances, acting as a sustained-release drug delivery system. [ABSTRACT FROM AUTHOR]

Acyclovir (ACY) is used to treat oral viral herpes but has low solubility and bioavailability. Stearic acid (SA) is lipophilic and can be combined with drugs. Therefore, this study aimed to characterize the properties of SA nanoparticles in increasing the cellular uptake of ACY by oral epithelial cells. The hypothesis was that SA nanoparticles increase sustained ACY release, are stable, and increase drug uptake. The production parameters (duration and amplitude of sonication) were optimized to produce solid lipid nanoparticles (SLN) of SA-containing ACY. Particle stability was characterized under different storage conditions (4 °C and 37 °C for 1, 15, and 45 days). SLN were further characterized for their pharmacokinetic profile, cytotoxicity, in vitro permeability, and ability to modulate gene expression and promote ACY uptake by oral epithelial cells. Pharmacokinetic studies revealed sustained and diffusional release of ACY from the SLN, with an initial burst release of 15 min. After 45 d of storage, SLN kept at both 4 °C and 37 °C showed a maximum release of > 90 % of the drug at 120 min. Cells treated with SLN presented a significantly higher intracellular drug content than those treated with ACY and significantly increased the genetic expression of TJP-1 , OCLN , and ECAD. The hypothesis was accepted as SA nanoparticles containing ACY can sustain drug delivery and enhance its absorption into epithelial cells. Therefore, SA nanoparticles are promising for improving ACY uptake in treating oral herpes and other infections caused by HSV-1. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer type and second leading cause of cancer‐related deaths worldwide, requiring novel drug‐delivery concepts. ITC@ZrO(TocP)/ZrO(FdUMP) core@shell nanocarriers (designated ITC‐FdUMP‐NC) with the clinically relevant chemotherapeutics irinotecan (ITC) and fluoro‐2′‐deoxyuridine‐5′‐phosphate (FdUMP) (active derivative of 5′‐fluorouracil/5‐FU) are a new type of nanocarrier with high drug payload (22 wt% of lipophilic ITC: particle core; 10 wt% of hydrophilic FdUMP: particle shell). The nanocarriers are tested in different CRC cell lines, a normal cell line, and rectal cancer patient‐derived organoids (PDOs). Fluorescence‐labeled nanocarriers show efficient uptake by all CRC cells and allow to distinctly track the intracellular trafficking toward endolysosomal compartments. Although free chemotherapeutic drugs exhibit a greater potency in 2D cell cultures, ITC‐FdUMP‐NC demonstrate equivalent cytotoxic efficacies as the freely dissolved drugs in the more complex 3D rectal cancer PDOs. The sustained drug‐release profile of the nanocarriers contrasts favorably with conventional free drugs, potentially enhancing the therapeutic outcome in vivo. With a chemotherapeutic cocktail comparable to the clinically applied FOLFIRI (ITC + 5‐FU), the ITC‐FdUMP‐NC represent a novel type of nanocarrier with high anti‐tumor effect and high drug payload, offering a promising strategy to circumvent chemoresistance and to improve therapy efficacy in vivo with less side effects. [ABSTRACT FROM AUTHOR]

Fe3O4 magnetic nanoparticles exhibit significant potential for cancer detection due to their unique magnetic properties and versatility. This review examines their role in enhancing cancer biomarker detection, focusing on synthesis methods, surface modifications and diagnostic accuracy. Fe3O4 nanoparticles serve as sensitive MRI contrast agents, facilitating early cancer diagnosis and improving patient prognosis. Synthesis techniques influence their properties, morphology and dimensions, which affect performance. Surface modifications enhance targeting and reduce immunological reactions, enabling precise biomarker detection and effective drug delivery to tumours, minimizing damage to healthy tissue. Despite these advantages, challenges remain in optimizing delivery efficiency and overcoming medication resistance. Further research is required to understand the pharmacokinetics and pharmacodynamics of these nanoparticles, including their distribution, metabolism and physiological impacts. This review provides insights into the potential of Fe3O4 magnetic nanoparticles as cancer detection agents, aiming to guide future research towards developing safer and more efficient applications in medical diagnostics and treatment. [ABSTRACT FROM AUTHOR]

The alarming rise in chronic diseases worldwide highlights the urgent need to overcome the limitations of conventional drug delivery systems. In this context, osmotic pumps are able to release drugs by differential osmotic pressure, achieving a controlled rate independent of physiological factors and reducing the dosing frequency. As osmotic pumps are based on the phenomenon of osmosis, the choice of high osmolality draw solutions (DSs) is a critical factor in the successful delivery of the target drug. Therefore, one alternative that has received particular attention is the formulation of DSs with magnetic nanoparticles (MNPs) due to their easy recovery, negligible reverse solute flux (RSF), and their possible tailor-made functionalization to generate high osmotic gradients. In this work, the possible integration of DSs formulated with MNPs in controlled drug delivery systems is discussed for the first time. In particular, the main potential advantages that these novel medical devices could offer, including improved scalability, regeneration, reliability, and enhanced drug delivery performance, are provided and discussed. Thus, the results of this review may demonstrate the potential of MNPs as osmotic agents, which could be useful for advancing the design of osmotic pump-based drug delivery systems. [ABSTRACT FROM AUTHOR]