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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.

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.

Graphene is the newest form of elemental carbon and it is becoming rapidly a potential candidate in the framework of nano‐bio research. Many reports confirm the successful use of graphene‐based materials as carriers of anticancer drugs having relatively high loading capacities compared with other nanocarriers. Here, the outcomes of a systematic study of the adsorption behavior of FDA approved PtII drugs cisplatin, oxaliplatin, and carboplatin on surface models of pristine, holey, and nitrogen‐doped holey graphene are reported. DFT investigations in water solvent have been carried out considering several initial orientations of the drugs with respect to the surfaces. Adsorption free energies, calculated including basis set superposition error (BSSE) corrections, result to be significantly negative for many of the drug@carrier adducts indicating that tested layers could be used as potential carriers for the delivery of anticancer PtII drugs. The reduced density gradient (RDG) analysis allows to show that many kinds of non‐covalent interactions, including canonical H‐bond, are responsible for the stabilization of the formed adducts. [ABSTRACT FROM AUTHOR]

[Display omitted] The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy of cancer faces several challenges. To address these limitations, we conducted an investigation to assess the potential of a cubosome formulation stabilized in water against coalescence utilizing a polyphosphoester analog of Pluronic F127 as a stabilizer and loaded with newly synthesized RPC-based photosensitizer [Ru(dppn) 2 (bpy-morph)](PF 6) 2 (bpy-morph = 2,2′-bipyridine-4,4′-diylbis(morpholinomethanone)), PS-Ru. The photophysical characterization of PS-Ru revealed its robust capacity to induce the formation of singlet oxygen (1O 2). Furthermore, the physicochemical analysis of the PS-Ru-loaded cubosomes dispersion demonstrated that the encapsulation of the photosensitizer within the nanoparticles did not disrupt the three-dimensional arrangement of the lipid bilayer. The biological tests showed that PS-Ru-loaded cubosomes exhibited significant phototoxic activity when exposed to the light source, in stark contrast to empty cubosomes and to the same formulation without irradiation. This promising outcome suggests the potential of the formulation in overcoming the drawbacks associated with the clinical use of RPCs in photodynamic therapy for anticancer treatments. [ABSTRACT FROM AUTHOR]

[Display omitted] • An injectable hydrogel to reduce the postoperative abdominal adhesion is designed. • A third-generation polyamide-amine dendrimer loads the Meloxicam for slow release. • The hydrogel has good in vitro and in vivo biosafety and biodegradability. • MX inhibits inflammatory responses and balances the fibrinolytic system. • The adhesion prevention is proved in a rat abdominal adhesion model. Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from ∼ 57.31 kPa to ∼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of ∼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management. [ABSTRACT FROM AUTHOR]

Introduction: Post-burn hypertrophic scars are an important cause of physical discomfort, limitation of movements, psychological disorders, low self-esteem and reduced quality of life. Treatment for this condition is complex and involves several options. Microneedling, also known as minimally invasive percutaneous collagen induction, is an affordable minimally invasive option that can be combined with other treatments, including ablative ones. Objective: The goal of this study was to present our microneedling approach for the treatment of hypertrophic scars after burns. Method: A prospective study of 15 patients with post-burn hypertrophic scars was conducted between October 2016 and June 2022. All patients were treated with microneedling and drug delivery of triamcinolone. Scars were evaluated using Vancouver Scar Scale (VSS), Burn Scar Assessment Scale (BSAS) and angle measurement for amplitude of movement evaluation of joints. Results: A significant improvement in the VSS score was obtained after microneedling (8.8 ± 0.44 to 4.1 ± 0.98; p = 0.012), especially in the acute group (less than 1 year after burns): 9.3 ± 0.49 to 3.5 ± 1.36; p = 0.041. There was a significant and progressive improvement of the scars throughout the treatment sessions in all criteria evaluated and in the ranges of joint movement (p = 0.012). Conclusion: Our microneedling protocol promoted a significant improvement of post-burn scars, especially in acute hypertrophic scars, and in the amplitude of joint motion. Sequential treatments provided progressive improvement. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

The repair and regeneration of cartilage is a challenge for scientists and clinical surgery. Achieving cell adhesion and regeneration, anti‐inflammatory, lubrication, targeted drug delivery and controlled release simultaneously in cartilage treatment are the goals of researchers. Polymer composites and hybrids have the potential to realize above functions in cartilage tissue engineering. This review refers to cartilage injuries, current clinical techniques, and their benefits and limitations, focusing on the most relevant and state of art of advanced polymers for cartilage tissue engineering. The frontier applications of multifunctional polymer composites and hybrids in cartilage tissue engineering are discussed in depth, including polymer scaffold, polymer bio‐lubricant, and zwitterionic polymer for drug delivery and sustained drug release. A summary of comprehensive properties of polymers such as processability, mechanical properties, biocompatibility, biodegradability, hydrophilicity, cytotoxicity, etc., and their mechanisms are analyzed. Furthermore, some key challenges and outstanding concerns on polymer‐based materials for cartilage tissue engineering are presented followed by future perspectives. Highlights: The state of art of advanced polymers for cartilage tissue engineering.The advanced bionic property and mechanism of polymer composites and hybrids.Polymers for scaffold, biolubricant, drug delivery, sustained drug release.Future perspectives on polymer composites, hybrids‐based cartilage materials. [ABSTRACT FROM AUTHOR]

The exploration of cell‐based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one‐step fusion process. We demonstrate doxorubicin (DOX)‐encapsulated liposomes conjugated with interleukin‐15 (IL‐15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models. [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]

Supramolecular gels are an important class of materials that are promising for its wide range of applications including drug delivery. While supramolecular gels are intrinsically porous because of the 3D nano‐matrix (gel matrix) that is being formed due to supramolecular self‐assembly process involving the gelator molecules during gelation, additional nanopores can be introduced to the overall gel if the gelator molecule itself holds molecular cavity such as metal‐organic‐cage (MOC) molecules. A MOC having the molecular formula [(Pd2L24).4NO3].3H2O.2DMF.MeOH (Pd‐cage) (L2=5‐Azido‐N,N′‐di‐pyridin‐3‐yl‐isophthalamide) was successfully synthesized and characterized by FT‐IR, 1H NMR, ESI‐MS and single crystal X‐ray diffraction. Stimuli‐reversible supramolecular metallogel PdG could easily be formed from Pd‐cage in DMSO/water mixture. The molecular cage of Pd‐cage was demonstrated to be available for loading an anti‐cancer drug namely doxorubicin (DOX). Subsequently, DOX was also loaded within PdG and delivered to melanoma cell line B16−F10 displaying significant anti‐cancer activity as revealed by both MTT and scratch assay. Rheoreversibility of PdG and its ability to load and deliver DOX to cancer cells clearly raised hope for developing this metallogel further as topical anticancer gel. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) remains a challenging chronic autoimmune disorder characterized by persistent joint inflammation and damage. While modern regenerative strategies, encompassing cell/stem cell-based therapies, gene therapy, and tissue engineering, have advanced tissue repair efforts, a definitive cure for RA remains elusive. Consequently, there is growing interest in developing targeted therapies that directly address the underlying mechanisms driving RA pathogenesis, such as extracellular vesicles (EVs). These small membrane-bound particles can modulate immune responses within the inflammatory microenvironment of damaged cartilage. To launch the clinical potential of EVs, they can be isolated from various cell types through several techniques. EVs can carry various bioactive molecules and anti-inflammatory or pro-regenerative drugs, deliver them directly to the affected joints, and affect the behavior of injured cells, making them a compelling choice for targeted therapy and drug delivery in RA patients. However, there are still several challenges and limitations associated with EV-based therapy, including the absence of standardized protocols for EV isolation, characterization, and delivery. This review provides a comprehensive overview of the cellular sources of EVs in RA and delves into their therapeutic potential and the hurdles they must overcome. [ABSTRACT FROM AUTHOR]

The research introduces a novel method for creating drug-loaded hydrogel beads that target anti-aging, anti-oxidative, and anti-inflammatory effects, addressing the interconnected processes underlying various pathological conditions. The study focuses on the development of hydrogel beads containing anti-aging compounds, antioxidants, and anti-inflammatory drugs to effectively mitigate various processes. The synthesis, characterization and in vitro evaluations, and potential applications of these multifunctional hydrogel beads are discussed. A polymeric alginate-orange peel extract (1:1) hydrogel was synthesized for encapsulating fish oil. Beads prepared with variable fish oil concentrations (0.1, 0.3, and 0.5 ml) were characterized, showing no significant decrease in size i.e., 0.5 mm and a reduction in pore size from 23 to 12 µm. Encapsulation efficiency reached up to 98% within 2 min, with controlled release achieved upto 45 to 120 min with increasing oil concentration, indicating potential for sustained delivery. Fourier-transform infrared spectroscopy confirmed successful encapsulation by revealing peak shifting, interaction between constituents. In vitro degradation studies showed the hydrogel's biodegradability improved from 30 to 120 min, alongside anti-inflammatory, anti-oxidative, anti-collagenase and anti-elastase activities, cell proliferation rate enhanced after entrapping fish oil. In conclusion, the synthesized hydrogel beads are a promising drug delivery vehicle because they provide stable and effective oil encapsulation with controlled release for notable anti-aging and regenerative potential. Targeted delivery for inflammatory and oxidative stress-related illnesses is one set of potential uses. Further research may optimize this system for broader applications in drug delivery and tissue engineering. [ABSTRACT FROM AUTHOR]

Despite clinical advances with protein kinase inhibitors (PKIs), oral administration of many PKIs is associated with highly variable plasma exposure and a narrow therapeutic window. We developed a novel hybrid nanoparticle‐amorphous solid dispersion (ASD) technology platform consisting of an amorphous PKI embedded in a polymer matrix. The technology was used to manufacture immediate‐release formulations of 2 tyrosine kinase inhibitors (TKIs), dasatinib and sorafenib. Our primary objective was to improve the absorption properties and reduce the pharmacokinetic (PK) variability of each TKI. The PKs of XS004 (dasatinib‐ASD, 100 mg tablet) and XS005 (sorafenib‐ASD, 2 × 50 mg capsules) were compared with their crystalline formulated reference drugs (140 mg of dasatinib‐reference and 200 mg of sorafenib‐reference). The in vitro biopharmaceutics of dasatinib‐ASD and XS005‐granulate showed sustained increased solubility in the pH range 1.2‐8.0 compared to their crystalline references. In vivo, XS004 was bioequivalent at a 30% lower dose and showed increased absorption and bioavailability, with 2.1‐4.8 times lower intra‐ and intersubject variability compared to the reference. XS005 had an increased absorption and bioavailability of 45% and 2.2‐2.8 times lower variability, respectively, but it was not bioequivalent at the investigated dose level. Taken together, the formulation platform is suited to generate improved PKI formulations with consistent bioavailability and a reduced pH‐dependent absorption process. [ABSTRACT FROM AUTHOR]

Graphene is a unique nanocarbon nanostructure which is commonly used to form the nanocomposites. Green strategies (chemical vapour deposition with green catalysts, mechanical exfoliation, sonication) and sustainable carbon sources (plant extracts and recycled polymers) have been applied to synthesise graphene and graphene derivatives. For the formation of graphene nanocomposites, green fabrication methods (sonication, solution route, electrostatic, in situ polymerisation, printing, hydrothermal, etc.) involving green matrices, nanofillers, solvents, and reagents, have also been investigated. Thus, this state-of-the-art overview highlights essential green methods for the formation of graphene and nanomaterials. The resulting green graphene nanocomposites have numerous superior structural and physical properties such as morphology, electrical conductivity, thermal conductivity, thermal stability, and mechanical stability. Subsequently, the green synthesised graphene and graphene nanocomposites have been explored for important high performance technical applications including the energy storage, packaging, antibacterial, bioimaging, and drug delivery applications. Future research on the development of advanced synthesis methods may overcome the design and performance challenges of the green graphene nanocomposites. [ABSTRACT FROM AUTHOR]

Polymer mechanochemistry has rapidly evolved since the mid‐2000s. Recent advancements highlight the development of mechanophore platforms for the controlled release of bioactive payloads and the exploration of biocompatible activation strategies. These platforms, ranging from furan‐maleimide Diels‐Alder adducts to disulfide motifs with β‐carbonate linkages, demonstrate promising prospects in targeted drug delivery. Additionally, supramolecular assemblies and free radical‐generating mechanophores present innovative avenues for potential therapeutic applications. Biocompatible activation methods, notably high‐intensity and/or low‐intensity focused ultrasound, hold potential for in vivo applications. However, challenges persist in comprehending the fundamental physics of ultrasound and its utilization for activation. Future directions emphasize the importance of simplicity in biocompatible platforms and polymer designs, stability under physiological conditions, and precise control of mechanical activation for enhanced biomedical and clinical utility. Despite the aforementioned chemical and technical obstacles, the outlook for polymer mechanochemistry in biomedical and clinical applications remains promising, urging continued exploration and advancement. Key Scientists: [ABSTRACT FROM AUTHOR]

To address the insufficiencies in the systemic research of calcium phosphate/alginate (ALG) microspheres for multi-drug delivery and bone formation, this study investigated the multi-drug release kinetics and osteogenic behaviors of β-tricalcium phosphate/ALG microspheres. The results showed that different loaded drugs exhibited an early burst release phenomenon, and the drug loading capacity decreased as the microsphere particle size decreased. In vitro cell proliferation and dead/live staining demonstrated that the microspheres had excellent cytocompatibility, and in vivo experiments demonstrated the microspheres' exceptional ability to enhance bone regeneration. [ABSTRACT FROM AUTHOR]

Effective healing and regeneration of various bone defects is still a major challenge and concern in modern medicine. Calcium phosphates have emerged as extensively studied bone substitute materials due to their structural and chemical resemblance to the mineral phase of bone, along with their versatile properties. Calcium phosphates present promising biological characteristics that make them suitable for bone substitution, but a critical limitation lies in their low osteoinductivity. To supplement these materials with properties that promote bone regeneration, prevent infections, and cure bone diseases locally, calcium phosphates can be biologically and therapeutically modified. A promising approach involves combining calcium phosphates with drug-containing liposomes, renowned for their high biocompatibility and ability to provide controlled and sustained drug delivery. Surprisingly, there is a lack of research focused on liposome-calcium phosphate composites, where liposomes are dispersed within a calcium phosphate matrix. This raises the question of why such studies are limited. In order to provide a comprehensive overview of existing liposome and calcium phosphate composites as bioactive substance delivery systems, the authors review the literature exploring the interactions between calcium phosphates and liposomes. Additionally, it seeks to identify potential interactions between calcium ions and liposomes, which may impact the feasibility of developing liposome-containing calcium phosphate composite materials. Liposome capacity to protect bioactive compounds and facilitate localized treatment can be particularly valuable in scenarios involving bone regeneration, infection prevention, and the management of bone diseases. This review explores the implications of liposomes and calcium phosphate material containing liposomes on drug delivery, bioavailability, and stability, offering insights into their advantages. [ABSTRACT FROM AUTHOR]

This article explores the field of nanomedicine and its potential applications in targeted drug delivery. It discusses the concept of "nanocarriers" that can transport drugs to specific organs and infected tissues, minimizing side effects. The article presents two experimental series that demonstrate the synthesis and loading of nanoparticles using polymers and various cargos. The experiments investigate the behavior of the nanoparticles in response to changes in pH, showing promising results for targeted drug delivery. The article highlights the educational opportunities and interdisciplinary connections that can be made through the teaching of nanomedicine in chemistry, biology, and physics classes. [Extracted from the article]

At the early stages of drug development, the amount of drug materials is rather limited. In this case, viscosity measurement is often postponed to the later stages, where grams of proteins can be produced. Therefore, it is necessary to develop a viscometer capable of measuring the viscosity with high accuracy while requiring low sample volume. This study presents a novel viscosity measurement technique based on measuring the resonance frequency and motional resistance of a micropillar-enhanced acoustic wave (μPAW) device. The μPAW was developed by fabricating micropillars on the quartz crystal microbalance substrate in order to achieve ultra-high sensitivity, thanks to a unique coupling between the micropillar and the resonator. The experimental measurements demonstrated a nonlinear relationship between the density and viscosity of the fluid and the response of μPAW. A calibration correlation was developed using the response of μPAW in aqueous glycerol and sucrose solutions. The measurements were then extended using high-concentration BSA solutions as the model of protein solution. The main advantage of the μPAW device in this work over other viscometers is the ability to simultaneously measure solution viscosity and protein adsorption on the surface. This is a huge step forward in the development of sensing systems for the pharmaceutical industry, where real-time sensing of target biological proteins and measuring the viscosity of a solution is required. [ABSTRACT FROM AUTHOR]

Malaria caused by Plasmodium protozoa, transmitted by the Anopheles mosquitoes' is one ofthe most important diseases. Current antimalarial drugs target vital parasite progressions ormetabolic pathways essential for parasitic development, thus aiding the host in overcomingthe infection by inhibiting protozoa growth. However, at the same time, it also produces adisruptive consequence on the host cells. These cause severe adverse effects on the host andlead to drug resistance. The urgent need for novel, non‐toxic anti‐protozoal compounds isevident due to the resistance developed against drugs like chloroquine andhydroxychloroquine. Metal complexes of various elements like iron, gold, ruthenium, and othershave shown their anti‐malarial potential. We have reviewed the research ongoing globally on the developments of new molecules of chloroquine coupled with different transition elements and describe the structure–activity relationship of chloroquine, which also provides insights into the chemistry of these compounds. [ABSTRACT FROM AUTHOR]

In this work, new pH‐sensitive and antibacterial drug carrier systems based on silver nanoparticles (AgNPs) embedded in the interlayer of laponite (Lap) in the presence of chitosan (CTS) for the controllable release of sunitinib maleate (STM) were developed. Silver ions and sunitinib maleate were first loaded into Lap, and the CTS‐based hybrid bionanocomposite carrier (Lap@CTS@AgNPs@STM) was obtained in the presence of citric acid as a cross‐linker agent. The successful preparation of nanocarrier and Ag NPs formation was thoroughly confirmed using techniques such as FTIR, XRD, TGA, SEM, and TEM. TEM images illustrated the excellent distribution of Ag NPs in the structure of Lap@CTS@AgNPs. The as‐prepared samples showed a pH‐sensitive anticancer drug release behavior. The STM release mechanism was studied using Korsmeyer–Peppas and Higuchi kinetic models. Furthermore, the in vitro cytotoxicity and antibacterial tests were carried out against both bacteria S. aureus and E. coli and MCF‐7 cell lines, respectively, to prove the effectiveness of synthesized samples as multifunctional carrier systems for biomedical applications. [ABSTRACT FROM AUTHOR]

To examine if 12.5 μl timolol maleate 0.5% microdrops dispensed with the Nanodropper Adaptor provide noninferior intraocular pressure (IOP) reduction compared with conventional 28 μl drops in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. Both eyes of subjects received 1 commercially available drop or both eyes of subjects received 1 microdrop of timolol maleate 0.5%. We measured IOP, resting heart rate (HR), and blood pressure (BP) at baseline and 1, 2, 5, and 8 hours after timolol administration. The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). Adaptor-mediated microdrops and conventional drops of timolol significantly decreased IOP compared with baseline at all timepoints. Noninferiority was established at 3 of 4 timepoints. Heart rate decreases with Nanodropper were approximately 3 beats per minute (bpm) less than with conventional drops. Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. Proprietary or commercial disclosure may be found after the references. [ABSTRACT FROM AUTHOR]

Objectives: To synthesize casein enzymatic hydrolysate (CEH)-laden gelatin methacryloyl (GelMA) fibrous scaffolds and evaluate the cytocompatibility and anti-inflammatory effects on dental pulp stem cells (DPSCs). Materials and methods: GelMA fibrous scaffolds with 10%, 20%, and 30% CEH (w/w) and without CEH (control) were obtained via electrospinning. Chemo-morphological, degradation, and mechanical analyses were conducted to evaluate the morphology and composition of the fibers, mass loss, and mechanical properties, respectively. Adhesion/spreading and viability of DPSCs seeded on the scaffolds were also assessed. The anti-inflammatory potential on DPSCs was tested after the chronic challenge of cells with lipopolysaccharides (LPS), followed by treatment with extracts obtained after immersing the scaffolds in α-MEM. The synthesis of the pro-inflammatory cytokines IL-6, IL-1α, and TNF-α was measured by ELISA. Data were analyzed by ANOVA/post-hoc tests (α = 5%). Results: CEH-laden electrospun fibers had a larger diameter than pure GelMA (p ≤ 0.036). GelMA scaffolds laden with 20% and 30% CEH had a greater mass loss. Tensile strength was reduced for the 10% CEH fibers (p = 0.0052), whereas no difference was observed for the 20% and 30% fibers (p ≥ 0.6736) compared to the control. Young’s modulus decreased with CEH (p < 0.0001). Elongation at break increased for the 20% and 30% CEH scaffolds (p ≤ 0.0038). Over time, DPSCs viability increased across all groups, indicating cytocompatibility, with CEH-laden scaffolds exhibiting greater cell viability after seven days (p ≤ 0.0166). Also, 10% CEH-GelMA scaffolds decreased the IL-6, IL-1α, and TNF-α synthesis (p ≤ 0.035). Conclusion: CEH-laden GelMA scaffolds facilitated both adhesion and proliferation of DPSCs, and 10% CEH provided anti-inflammatory potential after chronic LPS challenge. Clinical relevance: CEH incorporated in GelMA fibrous scaffolds demonstrated the potential to be used as a cytocompatible and anti-inflammatory biomaterial for vital pulp therapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Hydrogel containing viologen-based hyperbranched polyamide amines with dual drug loading capacity. • Wearable Patch (Patch-DT) uses hydrogel as the drug-carrying cathode and magnesium flakes as the anode. • Patch-DT enables release of two drugs simultaneously, overcoming the limitations of monotherapy. • Visible drug monitoring through wearable Patch's electrochromic properties. Wearable drug delivery systems (DDS) have made significant advancements in the field of precision medicine, offering precise regulation of drug dosage, location, and timing. The performance qualities that wearable DDS has always strived for are simplicity, efficiency, and intelligence. This paper proposes a wearable dual-drug synergistic release patch. The patch is powered by a built-in magnesium battery and utilizes a hydrogel containing viologen-based hyperbranched polyamidoamine as both a cathode material and an integrated drug reservoir. This design allows for the simultaneous release of both dexamethasone and tannic acid, overcoming the limitations of monotherapy and ensuring effective synergy for on-demand therapy. In a mouse model with praziquimod-induced psoriasis, the patch demonstrated therapeutic efficacy at a low voltage. The inflammatory skin returned to normal after 5 days with the on-demand release of dual drugs. This work provides a promising treatment option considering its straightforward construction and the therapeutic advantages of dual-drug synergy. [ABSTRACT FROM AUTHOR]

[Display omitted] Hydrophilic cationic drugs such as mitoxantrone hydrochloride (MTO) pose a significant delivery challenge to the development of nanodrug systems. Herein, we report the use of a hydrophobic ion-pairing strategy to enhance the nano-assembly of MTO. We employed biocompatible sodium cholesteryl sulfate (SCS) as a modification module to form stable ion pairs with MTO, which balanced the intermolecular forces and facilitated nano-assembly. PEGylated MTO-SCS nanoassemblies (pMS NAs) were prepared via nanoprecipitation. We systematically evaluated the effect of the ratio of the drug module (MTO) to the modification module (SCS) on the nanoassemblies. The increased lipophilicity of MTO-SCS ion pair could significantly improve the encapsulation efficiency (∼97 %) and cellular uptake efficiency of MTO. The pMS NAs showed prolonged blood circulation, maintained the same level of tumor antiproliferative activity, and exhibited reduced toxicity compared with the free MTO solution. It is noteworthy that the stability, cellular uptake, cytotoxicity, and in vivo pharmacokinetic behavior of the pMS NAs increased in proportion to the molar ratio of SCS to MTO. This study presents a self-assembly strategy mediated by ion pairing to overcome the challenges commonly associated with the poor assembly ability of hydrophilic cationic drugs. [ABSTRACT FROM AUTHOR]

The study aimed to develop, characterize, and evaluate matrix-type oral bi-layered mucoadhesive hydrogel membrane patches for the intestinal delivery of gliclazide. Surface pH, drug content, thickness, folding endurance, moisture content, water vapor transmission rate, and swellability of hydrogel membrane patches were found satisfactory. These patches were characterized by SEM, DSC, and FT-IR spectroscopy. In-vitro gliclazide release from these hydrogel membrane patches was sustained over 8 h. Ex-vivo study demonstrated good mucoadhesion of these hydrogel membrane patches. Therefore, these matrix-type oral bi-layered mucoadhesive-natured PNIPAM-co-MM/chitosan made-hydrogel membrane patches for intestinal delivery of gliclazide can be effectively used in type-II diabetes mellitus management. [ABSTRACT FROM AUTHOR]

B3LYP was employed as a density functional to inspect the impact of Mn doping on the ability of graphyne (Gr) in the delivery of the propylthiouracil (PTU) drug. The interaction between the pure Gr and PTU was weak. Doping of the Mn metal into the Gr surface raised the PTU adhesion energy from −6.1 to −28.3 kcal mol−1, and PTU prefers to attach through its O atom to an Mn of the Mn-doped Gr (Mn@Gr). The analysis of partial density-of-states demonstrated that Mn substantially contributes to generating the virtual orbitals of Mn@Gr. It indicates the suitability of Mn, in contrast to the C atoms of Gr, for the nucleophilic attack. In addition to substantial energy release, the electronic properties of Mn@Gr were appreciably sensitive to the attachment of PTU, making it possible for recognizing the trajectory of the drug. A drug release mechanism was provided in cancer tissues, demonstrating that in cancer cells with a low pH, PTU and Mn@Gr were protonated significantly, thus separating PTU from the surface of Gr. Finally, there was a change in the reaction mechanism of PTU with Mn@Gr from covalent bonding in the natural environment to the H-bonding in the acidic environment of cancerous cells. [ABSTRACT FROM AUTHOR]

Bacterial infections of the respiratory tract cause millions of deaths annually. Several diseases exist wherein (1) bacterial infection is the main cause of disease (e.g., tuberculosis and bacterial pneumonia), (2) bacterial infection is a consequence of disease and worsens the disease prognosis (e.g., cystic fibrosis), and (3) bacteria-triggered inflammation propagates the disease (e.g., chronic obstructive pulmonary disease). Current approaches to combat infections generally include long and aggressive antibiotic treatments, which challenge patient compliance, thereby making relapses common and contributing to the development of antibiotic resistance. Consequently, the proportion of infections that cannot be treated with conventional antibiotics is rapidly increasing, and novel therapies are urgently needed. In this context, antimicrobial peptides (AMPs) have received considerable attention as they may exhibit potent antimicrobial effects against antibiotic-resistant bacterial strains but with modest toxicity. In addition, some AMPs suppress inflammation and provide other host defense functions (motivating the alternative term host defense peptides (HDPs)). However, the delivery of AMPs is complicated because they are large, positively charged, and amphiphilic. As a result of this, AMP delivery systems have recently attracted attention. For airway infections, the currently investigated delivery approaches range from aerosols and dry powders to various self-assembly and nanoparticle carrier systems, as well as their combinations. In this paper, we discuss recent developments in the field, ranging from mechanistic mode-of-action studies to the application of these systems for combating bacterial infections in the airways. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intrapulmonary percussive ventilation (IPV) is frequently used for airway clearance, together with delivery of aerosolized medications. Drug delivery via IPV alone increases with decreasing percussion frequency and correlates with tidal volume (VT), whereas drug delivery via IPV during invasive ventilation is not well characterized. We hypothesized that drug delivery via IPV-invasive ventilation would differ from IPV alone due to control of ventilation by invasive ventilation. METHODS: An adult ventilator circuit was used for IPV-invasive ventilation. A normal or a diseased lung model was configured to airway resistance of 5 cm H2O/L/s and lung compliance of 100 mL/cm H2O or to airway resistance of 20 cm H2O/L/s and lung compliance of 50 mL/cm H2O, respectively. The ventilator settings were the following: pressure control continuous mandatory ventilation mode, 10 breaths/min; PEEP, 5 cm H2O; ..., 0.21; inspiratory time, 1 s; no bias flow; and inspiratory pressure, 10 or 15 cm H2O for the normal or the diseased lung model, respectively, to reach VT 500 mL with IPV off. Albuterol nebulized from an IPV device was captured in a filter placed before the lung model and quantitated by spectrophotometry. RESULTS: The maximum efficiency of albuterol delivery via IPV-invasive ventilation was not different from that via IPV alone (mean ± SD of loading dose, 3.7 ± 0.2% vs 4.2 ± 0.3%, respectively; P = .12). The mean ± SD albuterol delivery efficiency with IPV-invasive ventilation was lower for the diseased lung model versus the normal model (1.6 ± 0.3% vs 3.2 ± 0.5%; P < .001), which increased with decreasing percussion frequency. In contrast, the mean ± SD was lower for the normal lung model versus the diseased model (401 ± 14 mL vs 470 ± 11 mL; P < .001). CONCLUSIONS: Albuterol delivery via IPV-invasive ventilation was modulated by percussion frequency but was not increased with increasing VT. The delivery efficiency was not sufficiently high for clinical use, in part due to nebulizer retention and extrapulmonary deposition. [ABSTRACT FROM AUTHOR]

This work wants to investigate the potential of Cu-Si52, Cu-C52, Cu-Al26N26, Cu-doped nanotubes (6, 0) to adsorb and deliver the Favipiravir as COVID-19 drug by DSD-PBEPBE-D3/aug-cc-pVDZ method. This work aims to propose the suitable materials for drug delivery of Favipiravir as COVID-19 drug. Results indicated that the Cu adoption can be increased the stability of Si52, C52, Al26N26, SiNT (6, 0), CNT (6, 0) and AlNNT (6, 0), significantly. The ΔGadsorption of complexes of Favipiravir with Cu-Si52, Cu-C52, Cu-Al26N26, Cu-doped nanotubes (6, 0) are -3.14, -3.25, -3.40, -3.89, -4.03 and -4.13 eV, respectively. The recovery time (τ) values of complexes of Favipiravir with Cu-Si52, Cu-C52, Cu-Al26N26, Cu-doped nanotubes (6, 0) in gas phase are 50.0, 51.8, 55.0, 56.3, 58.3 and 63.0 s. The Cu-AlNNT (6, 0) and Cu-Al26N26 have higher recovery time (τ) than Cu-Si52, Cu-C52, Cu-doped nanotubes (6, 0). Results shown that the Cu-Si52, Cu-C52, Cu-Al26N26, Cu-doped nanotubes (6, 0) have higher capacitates and abilities to deliver and transfer of the Favipiravir than other nanostructures in previous works. Finally, the Cu-AlNNT (6, 0) and Cu-CNT (6, 0) are proposed as acceptable structures to deliver and transfer of Favipiravir as drug of Coronavirus disease. [ABSTRACT FROM AUTHOR]

Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases. [ABSTRACT FROM AUTHOR]

The piezoelectric micropump can be a prominent component of drug delivery systems due to its high performance, low cost, and faster response. However, backpressure remains to be the most common problem in micropump technology. Thus, microvalves or the passive check valve based piezoelectric micropump can be used to prevent the backpressure. However, the complex structure of the passive check valve based micropump limits the investigations of Fluid-Structure Interaction (FSI) due to the intricate Multiphysics involved. This paper presents the investigations on the flow behaviour and performance of a passive check valve based piezoelectric micropump using numerical analysis. The simulation study comprising FSI depicts the performance of a piezoelectric micropump using a fluid-structure coupling, fluid selection, structural modelling, and piezoelectric equations. The simulation results illustrate the micropump performance characteristics such as piezoelectric actuator displacement, micropump flow rate, backpressure, and Von Mises stress. Experiments are conducted to validate simulation results by studying the effect of voltage and frequency on the micropump flow and pressure characteristics. The experimental study demonstrated that the passive check valve based piezoelectric micropump delivers a maximum flow rate of 32 ml/min at zero backpressure. The micropump can pump the fluid against maximum backpressure up to 35 kPa. [ABSTRACT FROM AUTHOR]

In this study, a new targeted and controlled‐release drug delivery system based on graphene quantum dots (GQDs) was fabricated. The fluorescent GQDs were synthesized via an environmentally‐friendly chemical oxidation method, using graphene oxide (GO) as a precursor and hydrogen peroxide and ammonia solution as oxidants. Folic acid (FA), as a targeting agent, was bound to GQDs through strong amide covalent bindings, and tamoxifen (TMX), as a hydrophobic anticancer drug, was non‐covalently attached to the nanocarrier via π–π stacking bonds. The as‐prepared GQDs and TMX/FA‐GQDs were characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), UV/Vis spectroscopy (UV/Vis), and photoluminescence spectroscopy (PL). The resulting TMX/GQDs demonstrated pH‐sensitive release behaviour with an overall release of 85% and 58% at pH 5.5 and 7.4, respectively, after 120 h. Also, the MTT assay test performed on MCF‐7 cells presented negligible toxicity of the nanocarriers, even at high concentrations. At the same time, the targeted nanocarrier, TMX/FA‐GQDs, showed much more toxicity towards MCF‐7 cells than the non‐targeted one and free TMX. [ABSTRACT FROM AUTHOR]

Fluorouracil (5-FU) has been the most widely used chemotherapy agent since its clinical introduction in 1957, and it continues to form the basis of treatment for various cancers. However, due to the side effects of an antimetabolite, a strategy fulfilling stringent requirements placed on a 5-FU delivery system requires controlled and extended release of 5-FU in a localized manner. Here, an in-situ gel-forming method for the preparation of micropatterned, α-chymotrypsin-degradable hydrogel (PHcd) for controlled release of 5-FU is introduced. More specifically, methacrylated hyaluronic acid (HA) and polyethylene glycol diacrylate (PEGDA), known for their excellent moisture retention capacity, are chosen for skin therapy. They are crosslinked with CYKC peptide through a thiol-ene click reaction. The synthesis of the CYKC peptide and its cleavage by α-chymotrypsin were confirmed using high-performance liquid chromatography (HPLC). Additionally, the in vitro release behavior was accurately monitored using the micropatterning method, demonstrating the stable immobilization and successful sustained release of 5-FU upon the addition of α-chymotrypsin in micropatterned PHcd hydrogel. Consequently, this micropatterned PHcd hydrogel can be considered a promising scaffold for localized and sustained delivery of cytotoxic drugs for skin cancer treatment. [ABSTRACT FROM AUTHOR]

To overcome the poor targeting of conventional chemotherapeutic drugs and the defects of low drug‐loading capacity of conventional drug delivery systems, novel drug delivery systems with high drug‐loading capacity are developed. Herein, the high drug‐loaded mPEG79‐GFLGDDD‐DOX copolymer is first synthesized via an amide reaction, which can bond multiplex DOX. After PEGylation, the drug can resist the adsorption of proteins in the plasma in blood circulation, avoid being rapidly cleared out of the body, and prolong the circulation time of the drug in the blood, which is conducive to the enrichment of micelles in tumor tissues through the EPR effect. In tumor tissues, the peptide Glycine‐ Phenylalanine‐ Leucine‐ Glycine (GFLG) is recognized and sheared by overexpressed cathepsin B, which stripped the outer layer of methoxy polyethylene glycol (mPEG) and made it more readily available for uptake by tumor cells. After entering the tumor cells, the bonded DOX and the physically encapsulated DOX in the micelles played a synergistic role, realizing the killing of tumor cells, thus effectively enhancing the therapeutic effect on tumors. The findings in this work suggest that a high drug‐loading drug delivery system has great potential in the clinical treatment of tumors. [ABSTRACT FROM AUTHOR]

Arthritis is a significant health concern affecting over 528 million people globally, reducing quality of life. The chronic nature of arthritis, coupled with insufficient therapeutic effectiveness, recurrence, and adverse side effects, complicates its management. Hyaluronic acid (HA) has emerged as a promising solution due to its biocompatibility, non‐toxicity, and targeted drug delivery capabilities, being a key component of the cartilage extracellular matrix widely used in managing arthritis. HA's inherent viscoelastic property and ability to target CD44 have spurred interest in developing HA‐based systems for delivering drugs to manage arthritis. Hyaluronic acid nanoscaffolds (HA‐NSCfs) show improved outcomes over treatments, including enhanced drug uptake through receptor‐mediated targeting, prolonged retention in the synovium, reduced proinflammatory mediator expression, enhanced cartilage regeneration, reduced drug toxicity due to sustained release, and more cost‐effective treatments. This review highlights the rationale for using HA‐NSCfs for the management and advanced drug delivery systems in arthritis, emphasizing preclinical and clinical results. It discusses various solid‐lipid nanoparticles, hydroxyapatite nanoparticles, polyelectrolyte complexes, liposomes, bilosomes, drug‐polymer conjugates, hydrogels, inorganic nanoparticles, and polymer nanoparticles, etc reported for arthritis management. Additionally, the review identifies key challenges and offers suggestions to address them, ultimately highlighting the potential of HA‐NSCfs as a topical treatment for arthritis. [ABSTRACT FROM AUTHOR]

Cancer has emerged as a significant threat to human health. Nucleic acid therapeutics regulate the gene expression process by introducing exogenous nucleic acid fragments, offering new possibilities for tumor remission and even cure. Their mechanism of action and high specificity demonstrate great potential in cancer treatment. However, nucleic acid drugs face challenges such as low stability and limited ability to cross physiological barriers in vivo. To address these issues, various nucleic acid delivery vectors have been developed to enhance the stability and facilitate precise targeted delivery of nucleic acid drugs within the body. In this review article, we primarily introduce the structures and principles of nucleic acid drugs commonly used in cancer therapy, as well as their cellular uptake and intracellular transportation processes. We focus on the various vectors commonly employed in nucleic acid drug delivery, highlighting their research progress and applications in recent years. Furthermore, we propose potential trends and prospects of nucleic acid drugs and their carriers in the future. [ABSTRACT FROM AUTHOR]

HIV is one of the most threatening health conditions with a highly increasing rate, affecting millions of people globally, and from its time of discovery until now, its potential cure cannot be explicitly defined. This challenge of having no/low effective drugs for the subjected virus has called for serious attention in the scientific world of virus disease therapeutics. Most of these drugs yields low effectiveness due to poor delivery; hence, there is a need for novel engineering methods for efficient delivery. In this study, two nanomaterilas (graphene; GP, and fullerene; C60) were modelled and investigated with sulfur (S), selenium (Se), and oxygen (O) atoms, to facilitate the delivery of zidovudine (ZVD). This investigation was computationally investigated using the density functional theory (DFT), calculated at B3LYP functional and Gd3bj/Def2svp level of theory. Results from the frontier molecular orbital (FMO), revealed that the GP/C60_S_ZVD complex calculated the least energy gap of 0.668 eV, thus suggesting a favourable interactions. The study of adsorption energy revealed chemisorption among all the interacting complexes wherein GP/C60_S_ZVD complex (-1.59949 eV) was highlighted as the most interacting system, thereby proving its potential for the delivery of ZVD. The outcome of this research urges that a combination of GP and C60 modified with chalcogen particularly, O, S, and Se can aid in facilitating the delivery of zidovudine. [ABSTRACT FROM AUTHOR]

Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti‐vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next‐generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally. [ABSTRACT FROM AUTHOR]

The activation of cyclic GMP‐AMP (cGAMP) synthase (cGAS) and its adaptor, stimulator of interferon genes (STING), is known to reprogram the immunosuppressive tumor microenvironment for promoting antitumor immunity. To enhance the efficiency of cGAS‐STING pathway activation, macrophage‐selective uptake, and programmable cytosolic release are crucial for the delivery of STING agonists. However, existing polymer‐ or lipid‐based delivery systems encounter difficulty in integrating multiple functions meanwhile maintaining precise control and simple procedures. Herein, inspired by cGAS being a natural DNA sensor, a modularized DNA nanodevice agonist (DNDA) is designed that enable macrophage‐selective uptake and programmable activation of the cGAS‐STING pathway through precise self‐assembly. The resulting DNA nanodevice acts as both a nanocarrier and agonist. Upon local administration, it demonstrates the ability of macrophage‐selective uptake, endosomal escape, and cytosolic release of the cGAS‐recognizing DNA segment, leading to robust activation of the cGAS‐STING pathway and enhanced antitumor efficacy. Moreover, DNDA elicits a synergistic therapeutic effect when combined with immune checkpoint blockade. The study broadens the application of DNA nanotechnology as an immune stimulator for cGAS‐STING activation. [ABSTRACT FROM AUTHOR]

Microparticles are increasingly employed as drug carriers inside the human body. To avoid collision with environment, they reach their destination following a predefined trajectory. However, due to the various disturbances, tracking control of microparticles is stilla challenge. In this work, we propose to use an Adaptive Nonlinear PID (A-NPID) controller for trajectory tracking of microparticles. A-NPID allows the gains to be continuously adjusted to satisfy the performance requirements at different operating conditions. An in-vitro study is conducted to verify the proposed controller where a microparticle of 100μm diameter is put to navigate through an open fluidic reservoir with virtual obstacles. Firstly, a collision-free trajectory is generated using a path-planning algorithm. Secondly, the microparticle dynamic model, when moving under the influence of external forces, is derived, and employed to design the A-NPID control law. The proposed controller successfully allowed the particle to navigate autonomously following the reference collision-free trajectory in presence of varying environmental conditions. Moreover, the particle could reach its targeted position with a minimal steady-state error of 4μm. A degradation in the performance was observed when only a PID controller was used in the absence of adaptive terms. The results have been verified by simulation and experimentally. [ABSTRACT FROM AUTHOR]

Cancer is measured as a major threat to human life and is a leading cause of death. Millions of cancer patients die every year, although a burgeoning number of researchers have been making tremendous efforts to develop cancer medicine to fight against cancer. Owing to the complexity and heterogeneity of cancer, lack of ability to treat deep tumor tissues, and high toxicity to the normal cells, it complicates the therapy of cancer. However, bacterial derivative-mediated drug delivery has raised the interest of researchers in overcoming the restrictions of conventional cancer chemotherapy. In this review, we show various examples of tumor-targeting bacteria and bacterial derivatives for the delivery of anticancer drugs. This review also describes the advantages and limitations of delivering anticancer treatment drugs under regulated conditions employing these tumor-targeting bacteria and their membrane vesicles. This study highlights the substantial potential for clinical translation of bacterial-based drug carriers, improve their ability to work with other treatment modalities, and provide a more powerful, dependable, and distinctive tumor therapy. [ABSTRACT FROM AUTHOR]

Nanogel, nanosized hydrogel, can contribute to biomedical and pharmaceutical, especially in drug delivery, due to its enthralling properties. Small size, large surface area, hydrophilicity, and stimulus responsiveness of nanogel ameliorate tissue penetration, drug loading capacity, and targeted drug delivery. The current study prepared nanosized, pH-sensitive, biocompatible, and stable chitosan/polymethacrylic acid (CS/PMAA) based nanogels using MBA as a crosslinker and APS as an initiator. FTIR confirmed the reaction between functional groups to synthesize nanogels sufficiently in a spherical shape, as affirmed by a FESEM. DLS data revealed nanosized particles with a size range of 70–170 nm and a range of 6–13 for polydispersity index (PDI). A study showed that 2% of MBA crosslinker is sufficient to achieve the desired crosslinking in 60 minutes reaction time (RT) with nanogel size ~ 92 nm. Increasing RT from 30 to 80 minutes during nanogel synthesis demonstrated a decrease in nanogel sizes from 186–73 nm. Synthesized nanogels have shown pH sensitivity (stimuli responsiveness) in acidic and alkaline mediums with an increase in particle size in pH-2 (~144 nm) and pH-8 (~280 nm) compared to intermediate pHs. The pH sensitivity of nanogels by changing the size per the suspended medium’s pH is crucial for prolonged systemic circulation and targeted drug delivery. Moreover, nanogels have shown good colloidal stability with zeta potential (ZP) +28 mv in acidic and −38 mv alkaline mediums. DSC and XRD results demonstrated thermal stability and amorphous morphology of nanogels, respectively. BET surface analysis revealed the surface area of nanogels in the range of 65–68 cm2/g with an average pore size of 28–32 nm. In-vitro cytotoxicity in the L-929 cell line by MTT assay established the cell viability (>70%) after 24 hours of incubation, substantiating the non-toxicity and biocompatibility of nanogels as nanocarriers for drug delivery. [ABSTRACT FROM AUTHOR]

AbstractOur previous clinical observations showed that platelet rich fibrin (PRF) can be used to deliver antibiotics to attenuate postoperative complications after unilaterally impacted mandibular third molar surgery (IMTMS). In order to begin understanding the mechanism involved in the beneficial in vivo effects of PRF-mediated delivery of antibiotics, in vitro studies were performed, which showed that PRF preparations containing amoxicillin/clavulanic acid or clindamycin significantly inhibited the growth of S. aureus bacteria. In our previous study, comparisons were made between control and treated groups. However, since variations among individual patients could possibly affect the results, the current study included patients with bilaterally symmetric impacted mandibular third molars, allowing us to compare control and antibiotic treatment within each patient. The effects of PRF preparations containing amoxicillin/clavulanic acid or clindamycin on IMTMS was tested in 60 clinical cases. Antibiotic-injected PRF treatment after bilaterally IMTMS resulted in significantly reduced pain, less use of analgesics, and reduced swelling and trismus compared to the control group (PRF without antibiotics) confirming our previous results after unilaterally IMTMS. The in vitro results support the hypothesis that in vivo delivery of antibiotics using PRF produces therapeutic effects after IMTMS by attenuating bacterial infection and inflammation. [ABSTRACT FROM AUTHOR]

Advancement in nanotechnology paves new way in nanomedicine via synthesis of various scaffolds bearing multifunctionalities having characteristics of both as diagnostic and therapeutic applications. Quantum dots (QDs) with exceptional luminescent properties exhibited some unbeatable characteristics of small size with ease in surface modifications and thus make them suitable candidates to be used in drug delivery and diagnosis of diseases. Meanwhile, various type of peptides are known in literature for their excellent therapeutic properties and thus make them promising candidates to be used as conjugate partner with the QDs. Highly luminescent properties and surface modifications flexibility of QDs, further urge to use them as promising conjugate partner with many small molecules including peptides and thus found applications in the field of nanomedicines. Thus Peptides ‐QDs conjugates exhibited the properties of both QDs and bioactivity, biocompatibility features of peptides and hence leave behind the limitation of both the individual partners (i. e. QDs and peptides). Thus the combined Peptides‐QDs conjugates acts as theranostic agent for various diseases where these acts as both imaging and drug delivery agent. Hence the present review focused on the theranostic applications of the Peptides‐QDs conjugates in various area of the nanomedicines. Also we focus on the area of improvement and advancement in nanomedicines for the diagnosis and treatment of the diseases in the early stages. [ABSTRACT FROM AUTHOR]

Epothilone B (Epo B), a promising antitumor compound effective against various types of cancer cells in vitro. However, its poor selectivity for tumor cells and inadequate therapeutic windows significantly limit its potential clinical application. Affibody is a class of non-immunoglobulin affinity proteins with precise targeting capability to overexpressed molecular receptors on cancer cells, has been intensively investigated due to its exceptional affinity properties. In this study, we present a targeted nanoagent self-assembled from the precursor of an affibody conjugated with Epo B via a linker containing the thioketal (tk) group that is sensitive to reactive oxygen species (ROS). The core-shell structure of the ZHER2:342-Epo B Affibody-Drug Conjugate Nanoagent (Z-E ADCN), with the cytotoxin Epo B encapsulated within the ZHER2:342 affibody corona, leads to significantly reduced side effects on normal organs. Moreover, the abundant presence of ZHER2:342 on the surface effectively enhances the targeting capacity and tumor accumulation of the drug. Z-E ADCN can be internalized by cancer cells via HER2 receptor-mediated endocytosis followed by Epo B release in response to high levels of ROS, resulting in excellent anticancer efficacy in HER2-positive tumor models. [ABSTRACT FROM AUTHOR]

Ischemic stroke poses significant challenges in terms of mortality and disability rates globally. A key obstacle to the successful treatment of ischemic stroke lies in the limited efficacy of administering therapeutic agents. Leveraging the unique properties of nanoparticles for brain targeting and crossing the blood–brain barrier, researchers have engineered diverse nanoparticle-based drug delivery systems to improve the therapeutic outcomes of ischemic stroke. This review provides a concise overview of the pathophysiological mechanisms implicated in ischemic stroke, encompassing oxidative stress, glutamate excitotoxicity, neuroinflammation, and cell death, to elucidate potential targets for nanoparticle-based drug delivery systems. Furthermore, the review outlines the classification of nanoparticle-based drug delivery systems according to these distinct physiological processes. This categorization aids in identifying the attributes and commonalities of nanoparticles that target specific pathophysiological pathways in ischemic stroke, thereby facilitating the advancement of nanomedicine development. The review discusses the potential benefits and existing challenges associated with employing nanoparticles in the treatment of ischemic stroke, offering new perspectives on designing efficacious nanoparticles to enhance ischemic stroke treatment outcomes. [ABSTRACT FROM AUTHOR]

Considerable progress has been made in the development of drug delivery systems for diabetic wounds. However, underlying drawbacks, such as low delivery efficiency and poor tissue permeability, have rarely been addressed. In this study, a multifunctional biohybrid nanorobot platform comprising an artificial unit and several biological components is constructed. The artificial unit is a magnetically driven nanorobot surface modified with antibacterial 2‐hydroxypropyltrimethyl ammonium chloride chitosan, which enables the entire platform to move and has excellent tissue penetration capacity. The biological components are two‐step engineered extracellular vesicles that are first loaded with mangiferin, a natural polyphenolic compound with antioxidant properties, and then glycoengineered on the surface to enhance cellular uptake efficiency. As expected, the platform is more easily absorbed by endothelial cells and fibroblasts and exhibits outstanding dermal penetration performance and antioxidant properties. Encouraging results are also observed in infected diabetic wound models, showing improved wound re‐epithelialization, collagen deposition, angiogenesis, and accelerated wound healing. Collectively, a biohybrid nanorobot platform that possesses the functionalities of both artificial units and biological components serves as an efficient delivery system to promote diabetic wound repair through dual‐enhanced cell and tissue penetration and multistep interventions. [ABSTRACT FROM AUTHOR]