Delivery Capability Research Articles

Space Station-like Composite Nanoparticles for Co-Delivery of Multiple Natural Compounds from Chinese Medicine and Hydrogen in Combating Sensorineural Hearing Loss.

Ototoxic drugs such as aminoglycoside antibiotics and cisplatin (CDDP) can cause sensorineural hearing loss (SNHL), which is closely related to oxidative stress and the acidification of the inner ear microenvironment. Effective treatment of SNHL often requires multifaceted approach due to the complex pathology, and drug combination therapy is expected to be at the forefront of modern hearing loss treatment. Here, space-station-like composite nanoparticles (CCC@mPP NPs) with pH/oxidation dual responsiveness and multidrug simultaneous delivery capability were constructed and then loaded with various drugs including panax notoginseng saponins (PNS), tanshinone IIA (TSIIA), and ammonia borane (AB) to provide robust protection against SNHL. Molecular dynamics simulation revealed that carboxymethyl chitosan/calcium carbonate-chitosan (CCC) NPs and monomethoxy poly(ethylene glycol)-PLGA (mPP) NPs can rendezvous and dock primarily by hydrogen bonding, and electrostatic forces may be involved. Moreover, CCC@mPP NPs crossed the round window membrane (RWM) and entered the inner ear through endocytosis and paracellular pathway. The docking state was basically maintained during this process, which created favorable conditions for multidrug delivery. This nanosystem was highly sensitive to pH and reactive oxygen species (ROS) changes, as evidenced by the restricted release of payload at alkaline condition (pH 7.4) without ROS, while significantly promoting the release in acidic condition (pH 5.0 and 6.0) with ROS. TSIIA/PNS/AB-loaded CCC@mPP NPs almost completely preserved the hair cells and remained the hearing threshold shift within normal limits in aminoglycoside- or CDDP-treated guinea pigs. Further experiments demonstrated that the protective mechanisms of TSIIA/PNS/AB-loaded CCC@mPP NPs involved direct and indirect scavenging of excessive ROS, and reduced release of pro-inflammatory cytokines. Both in vitro and in vivo experiments showed the high biocompatibility of the composite NPs, even after long-term administration. Collectively, this work suggests that composite NPs is an ideal multi-drug-delivery vehicle and open new avenues for inner ear disease therapies.

A multifunctional ‘golden cicada’ nanoplatform breaks the thermoresistance barrier to launch cascade augmented synergistic effects of photothermal/gene therapy

BackgroundPhotothermal therapy (PTT) is taken as a promising strategy for cancer therapy, however, its applicability is hampered by cellular thermoresistance of heat shock response and insufficient accumulation of photothermal transduction agents in the tumor region. In consideration of those limitations, a multifunctional “Golden Cicada” nanoplatform (MGCN) with efficient gene delivery ability and excellent photothermal effects is constructed, overcoming the thermoresistance of tumor cells and improving the accumulation of indocyanine green (ICG).ResultsDown-regulation of heat shock protein 70 (HSP70) makes tumor cells more susceptible to PTT, and a better therapeutic effect is achieved through such cascade augmented synergistic effects. MGCN has attractive features with prolonged circulation in blood, dual-targeting capability of CD44 and sialic acid (SA) receptors, and agile responsiveness of enzyme achieving size and charge double-variable transformation. It proves that, on the one hand, MGCN performs excellent capability for HSP70-shRNA delivery, resulting in breaking the cellular thermoresistance mechanism, on the other hand, ICG enriches in tumor site specifically and possesses a great thermal property to promoted PTT.ConclusionsIn short, MGCN breaks the protective mechanism of cellular heat stress response by downregulating the expression of HSP70 proteins and significantly augments synergistic effects of photothermal/gene therapy via cascade augmented synergistic effects.

Supramolecular assemblies with spatio-temporal sequential drug delivery capability treat spinal cord injury via neuroprotection and immunoregulation

Spinal cord injury (SCI) can result in irreversible motor and sensory deficits. However, up to data, clinical first-line drugs have ambiguous benefits and debilitating side effects, mainly due to the insufficient accumulation, poor physiological barrier penetration, and lack of spatio-temporal controlled release at lesion tissue. Herein, we proposed a supramolecular assemblies composed of hyperbranched polymer-formed core/shell structure through host-guest interactions. Such HPAA-BM@CD-HPG-C assemblies co-loaded with p38 inhibitor (SB203580) and insulin-like growth factor 1(IGF-1) are able to achieve time- and space-programmed sequential delivery benefiting from their cascaded responsiveness. The core-shell disassembly of HPAA-BM@CD-HPG-C occurs in acidic micro-environment around lesion, achieving preferentially the burst release of IGF-1 to protect survival neurons. Subsequently, the HPAA-BM cores containing SB203580 are endocytosed by the recruited macrophages and degraded by intracellular GSH, accelerating the release of SB203580 to promote the conversion from M1 to M2 macrophage. Hence, the successive synergy of neuroprotection and immunoregulation effects contribute to subsequent nerve repair and locomotor recovery as demonstrated in vitro and in vivo studies. Thus, our fabrication provides a strategy that multiple drugs co-delivery in a spatio-temporal selective manner adapting to the disease progression through self-cascaded disintegration, are expected to realize multidimensional precise treatment of SCI.

Monitoring Disassembly and Cargo Release of Phase-Separated Peptide Coacervates with Native Mass Spectrometry.

Engineering liquid-liquid phase separation (LLPS) of proteins and peptides holds great promise for the development of therapeutic carriers with intracellular delivery capability but requires accurate determination of their assembly properties in vitro, usually with fluorescently labeled cargo. Here, we use mass spectrometry (MS) to investigate redox-sensitive coacervate microdroplets (the dense phase formed during LLPS) assembled from a short His- and Tyr-rich peptide. We can monitor the enrichment of a reduced peptide in dilute phase as the microdroplets dissolve triggered by their redox-sensitive side chain, thus providing a quantitative readout for disassembly. Furthermore, MS can detect the release of a short peptide from coacervates under reducing conditions. In summary, with MS, we can monitor the disassembly and cargo release of engineered coacervates used as therapeutic carriers without the need for additional labels.

Local Sustained Chemotherapy of Pancreatic Cancer Using Endoscopic Ultrasound-Guided Injection of Biodegradable Thermo-Sensitive Hydrogel.

Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI. A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining. GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well. The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.

On‐Demand Inkjet Printed Hydrophilic Coatings for Flow Control in 3D‐Printed Microfluidic Devices Embedded with Organic Electrochemical Transistors

AbstractMicrofluidic surface chemistry can enable control of capillary‐driven flow without the need for bulky external instrumentation. A novel pondered nonhomogeneous coating defines regions with different wetting properties on the microchannel walls. It changes the curvature of the liquid–air meniscus at various channel cross‐sections and consequently leads to different capillary pressures, which is favorable in the strive toward automatic flow control. This is accomplished by the deposition of hydrophilic coatings on the surface of multilevel 3D‐printed (3DP) microfluidic devices via inkjet printing, thereby retaining the surface hydrophilicity for at least 6 months of storage. To the best of our knowledge, this is the first demonstration of capillary flow control in 3DP microfluidics enabled by inkjet printing. The method is used to create “stop” and “delay” valves to enable preprogrammed capillary flow for sequential release of fluids. To demonstrate further utilization in point‐of‐care sensing applications, screen printed organic electrochemical transistors are integrated within the microfluidic chips to sense, sequentially and independently from external actions, chloride anions in the (1–100) × 10−3 m range. The results present a cost‐effective fabrication method of compact, yet comprehensive, all‐printed sensing platforms that allow fast ion detection (<60 s), including the capability of automatic delivery of multiple test solutions.

Development of an antibacterial and antioxidative nanofibrous membrane using curcumin-loaded halloysite nanotubes for smart wound healing: In vitro and in vivo studies

Endowing wound dressings with drug delivery capability is a suitable strategy to transfer medicinal compounds locally to damaged skin layers. These dressings are especially useful for accelerating the healing rate in the cases of long-term treatment, and adding more functionalities to the platform. In this study, a wound dressing composed of polyamide 6, hyaluronic acid, and curcumin-loaded halloysite nanotubes (PA6/HA/HNT@Cur) was designed and fabricated for wound healing applications. The physicochemical properties of this platform were investigated through Fourier-transform infrared spectroscopy and field-emission scanning electron microscopy. Moreover, wettability, tensile strength, swelling, and in vitro degradation were assessed. The HNT@Cur was incorporated in the fibers in three concentrations and 1 wt% was found as the optimum concentration yielding desirable structural and mechanical properties. The loading efficiency of Cur on HNT was calculated to be 43 ± 1.8%, and the release profiles and kinetics of nanocomposite were investigated at physiological and acidic pH. In vitro antibacterial and antioxidation studies showed that the PA6/HA/HNT@Cur mat had strong antibacterial and antioxidation activities against gram-positive and -negative pathogens and reactive oxygen species, respectively. Desirable cell compatibility of the mat was found through MTT assay against L292 cells up to 72 h. Finally, the efficacy of the designed wound dressing was evaluated in vivo; after 14 days, the results indicated that the wound size treated with the nanocomposite mat significantly decreased compared to the control sample. This study proposed a swift and straightforward method for developing materials that might be utilized as wound dressings in clinical settings.

Achieving Minimum Deterrence: A New Dyadic Dataset on Strategic Nuclear Weapons Delivery Capabilities

This paper argues that existing quantitative studies mistakenly assume that all nuclear states can impose nuclear destruction on opponents by simply distinguishing nuclear states from non-nuclear states. This practice, however, does not capture variation in 1) nuclear states’ possession of delivery capabilities, 2) the range of deployed nuclear delivery systems, and 3) the geographic distance between nuclear states and their dyadic counterparts. Instead of this monadic nuclear statehood approach, I propose the dyadic nuclear reach approach, which uses a new dyad-specific measure of states’ strategic nuclear delivery capabilities. It codes whether a nuclear state can launch a nuclear strike against a given opponent by using the information about the estimated range of each nuclear state’s strategic nuclear delivery platforms, nuclear operation bases, and states’ capital cities. An empirical application shows that using an appropriate measure of nuclear capabilities does significantly alter existing empirical knowledge of nuclear weapons and international conflict.

The Promise of Exosomes as Drug Delivery Systems

Exosomes are small extracellular vesicles that play a role in cell-to-cell communication by transferring bioactive molecules such as proteins, nucleic acids, and lipids between cells. Over the past few years, there have been significant advances in utilizing exosomes as drug delivery systems due to their unique properties, including their ability to target specific cells and tissues. Especially advances in targeted delivery, nanoparticle incorporation, personalized medicine, cargo delivery, imaging, and tracking have excited the pharmaceutical community about their potential use in these areas. I briefly discuss the significance of exosomes in these areas or research interests. Natural Cargo Delivery: Exosomes naturally transport a variety of biomolecules, making them attractive vehicles for delivering drugs, nucleic acids (such as siRNA and miRNA), proteins, and even small molecules. Researchers are harnessing this inherent cargo delivery capability to load exosomes with therapeutic agents. Engineered Exosomes: Scientists are engineering exosomes to enhance their drug delivery capabilities. This includes modifying the surface of exosomes to display targeting ligands that can direct them to specific cell types or tissues, improving their stability, and optimizing their cargo-loading efficiency. Targeted Delivery: One of the key advantages of using exosomes for drug delivery is their potential for targeted delivery. By engineering exosomes to carry targeting molecules on their surface, researchers can selectively deliver therapeutic agents to specific cells or disease sites, minimizing off-target effects. Personalized Medicine: Exosomes can be isolated from a patient's cells (autologous exosomes), loaded with personalized therapies, and then re-administered to the patient. This personalized approach holds promise for tailoring treatments to individual patients' needs. Imaging and Tracking: Exosomes can be labeled with imaging agents to track their distribution and uptake in vivo. This information is crucial for understanding the pharmacokinetics and biodistribution of exosome-based drug delivery systems. Nanoparticle Incorporation: Exosomes can be loaded with nanoparticles, such as liposomes or polymer-based carriers, to increase their cargo capacity and control drug release kinetics. This combination allows for synergistic benefits of both exosome-mediated and nanoparticle-based drug delivery. Clinical Translation: Clinical trials involving exosome-based therapies are underway for various diseases, including cancer and neurodegenerative disorders. These trials provide valuable insights into the safety, efficacy, and challenges associated with exosome-based drug delivery in humans. Regulatory Considerations: The field of exosome-based drug delivery is also evolving in terms of regulatory considerations. Regulatory agencies are working to establish guidelines and standards for developing and approving exosome-based therapies. Exosome Isolation and Purification Techniques: Advances in exosome isolation and purification methods are critical for obtaining high-quality and consistent exosome preparations for drug delivery studies. Improved techniques contribute to the reproducibility and reliability of exosome-based therapies. Disease-Specific Cargo: Exosomes derived from specific cell types or disease models can be isolated and used as delivery vehicles for disease-specific cargo, including diagnostic biomarkers and therapeutic agents. This enables precise delivery to disease-affected cells. Combination Therapies: Researchers are exploring the potential of using exosomes to deliver combination therapies, where multiple therapeutic agents are loaded into a single exosome to achieve synergistic effects. The study of exosomes as drug delivery systems is rapidly advancing and holds great promise for improving the targeted delivery of therapeutic agents, reducing side effects, and enabling personalized medicine approaches. However, scalability, cargo loading efficiency, safety, and regulatory approval challenges still need to be addressed as the field progresses.

Modelling of Bi-Directional Buck-Boost Converter for Electric Vehicle

Abstract: The rapid growth of electric vehicles (EVs) has necessitated the development of efficient and versatile energy storage systems. In this study, we present the modelling and implementation of a switching bi-directional buck-boost converter based on electric vehicle hybrid energy storage. The proposed converter offers a flexible and reliable solution for managing energy flow between different storage elements in an EV, such as batteries and ultra-capacitors. First, a comprehensive mathematical model of the converter is developed, taking into account the dynamic behaviour of the energy storage components. This model enables us to analyse and optimize the converter's performance in terms of efficiency, voltage regulation, and power delivery capabilities. Furthermore, simulation studies are conducted to validate the accuracy of the model and assess the converter's performance under various operating conditions. Based on the modelling and simulation results, a practical implementation of the converter is carried out using high-quality electronic components. The design considerations, including component selection, circuit layout, and control strategy, are discussed in detail. The implemented converter is then evaluated experimentally to validate its performance and verify the effectiveness of the proposed modelling approach. The results demonstrate that the switching bidirectional buck-boost converter effectively manages the energy flow between the different storage elements in the hybrid energy storage system. It achieves high conversion efficiency, voltage regulation, and power transfer capabilities, enhancing the overall performance and range of electric vehicles. The developed model and implementation provide valuable insights for the design and optimization of similar converter topologies for electric vehicle applications. Overall, this study contributes to the advancement of energy storage systems in electric vehicles, facilitating the adoption of sustainable and efficient transportation solutions in the future

Codelivery of afuresertib and celecoxib by IL4RPep-1-targeting nanoparticles for effective treatment against melanoma

Melanoma is one of the most aggressive and deadly forms of skin cancer, and effective treatments need to be developed. The combination of chemoimmunotherapy has emerged as a promising strategy for treating cancer. However, this strategy still has several limitations, including the inability of more than two drugs to reach tumor tissue simultaneously and the risk of serious adverse effects. The use of nanodrug delivery systems is an effective method to successfully combine these therapies, as they reduce side effects and improve bioavailability. In this study, we developed IL4RPep-1-targeting peptide nanoparticles (IPP NPs) for the codelivery of afuresertib and celecoxib for melanoma treatment by taking advantage of the high drug loading capacity and favorable pharmacokinetic profile of the poly(lactide-co-glycolide) nanoparticle platform. IPP NPs efficiently target three different types of melanoma cells in vitro and significantly accumulate at the tumor site in vivo. ​In both ectopic and pulmonary metastatic melanoma models, targeted codelivery of afuresertib and celecoxib not only promotes melanoma cell apoptosis but also reprograms M2-type macrophages into M1-type macrophages, reconstructing the tumor immune microenvironment and activating the immune response against cancer cells. In addition, this highly coordinated precise delivery of the drug to tumor cells significantly reduces adverse reactions associated with the combination of afuresertib and celecoxib. In summary, IPP NPs exhibit an accurate pH response and ideal targeted drug delivery capabilities for combination chemotherapy and immunotherapy, offering therapeutic potential for this combination in melanoma.

Optimized Design of a Multistage Centrifugal Pump Based on Volumetric Loss Reduction by Auxiliary Blades

Throat ring leakage is a major factor deteriorating the performance of multistage centrifugal pumps. This paper focuses on the optimization of multistage centrifugal pumps by incorporating the principle of the Tesla valve and adding an auxiliary set of blades to the impeller body. By changing the direction and magnitude of the leaking fluid’s flow, the leakage volume of the impeller throat ring is reduced. The study results demonstrate that the experimental error in head calculation with numerical simulation at the optimal working condition was 0.65%, verifying the accuracy of the numerical simulation method. The leakage volume of the throat ring decreased by up to approximately 28.99% compared to the original structure, which significantly increased the pump’s head and overall efficiency. Near the optimal operating point, the pump’s head and overall efficiency increased by approximately 8.1% and 8.7%, respectively. The larger the flow rate, the greater the improvement in the pump’s head and total efficiency. Near high-flow operating conditions, the pump’s head and overall efficiency increased by approximately 116.45% and 110.84%, respectively. The auxiliary blade structure introduces a non-contact seal which, compared to traditional seal structures, improves seal life and reduces seal costs. Additionally, the auxiliary blades can shift the optimal operating point of the multistage centrifugal pump towards a higher flow rate, improving the pump’s delivery capability.

Tumbler‐Inspired Microneedle Containing Robots: Achieving Rapid Self‐Orientation and Peristalsis‐Resistant Adhesion for Colonic Administration

AbstractMicroneedle containing miniature robots offer a promising route for gastrointestinal administration since their capability of transmucosal delivery and controllable drug release. However, many challenges still lie ahead such as the intricate control modes, destitute systematic theory of the locomotion and adhesion behaviors, failure due to peristalsis and fluid flow, and risk of ileus. Herein, an untethered microneedle containing robots is designed for specific colonic administration, which can dispense with control systems, achieve fast self‐orientation and adhesion onto the mucosa (<0.6 s), against physiology of peristalsis, and show low risks of obstruction. Further, the detachable layer between the microneedle and the robots can degrade under a time of 6 min, which ensures safely discharge under a small, excreted force of 20 mN induced by fluid flow. Through the optimism of microneedles, different drug release times can be achieved including 14 min, 2 days, 4 days, and 30 days, respectively. The in vivo experiments also demonstrate the effectiveness and feasibility of the robots. These robots can serve as a versatile platform to treat diseases such as chronic inflammation and cancer of the colon to minimize invasive surgical intervention and patient suffering.

Impact of System-F in Delivering Vascular Plugs for Aortic Side Branch Embolization During Endovascular Aneurysm Repair.

This study aimed to illustrate the utility of our original system to deliver vascular plugs into aortic side branches during endovascular aneurysm repair (EVAR). Our device, which we named "System-F," consists of a 14 Fr sheath, a 12 Fr long sheath with a side hole, a stiff guidewire as a shaft, and a parallelly-inserted delivery catheter navigated through the side hole into the aneurysm sac. Vertical motion and horizontal rotation of the side hole allow multidimensional movement of the delivery catheter within the aneurysm. This system was applied in 7 cases undergoing EVAR; 4 inferior mesenteric arteries and 14 lumbar arteries were embolized using vascular plugs. Type II endoleak (T2EL) was not observed in the follow-up survey of any case. Conclusion: The applicability of System-F for vascular plug placement in the side branches of abdominal aortic aneurysms has the potential to achieve high delivery capability and be widely applied for the prevention of T2EL. System-F has potential to change the strategies of pre-EVAR embolization.

Layered Double Hydroxides: A Novel Promising 2D Nanomaterial for Bone Diseases Treatment.

Bone diseases including bone defects, bone infections, osteoarthritis, and bone tumors seriously affect life quality of the patient and bring serious economic burdens to social health management, for which the current clinical treatments bear dissatisfactory therapeutic effects. Biomaterial-based strategies have been widely applied in the treatment of orthopedic diseases but are still plagued by deficient bioreactivity. With the development of nanotechnology, layered double hydroxides (LDHs) with adjustable metal ion composition and alterable interlayer structure possessing charming physicochemical characteristics, versatile bioactive properties, and excellent drug loading and delivery capabilities arise widespread attention and have achieved considerable achievements for bone disease treatment in the last decade. However, to the authors' best knowledge, no review has comprehensively summarized the advances of LDHs in treating bone disease so far. Herein, the advantages of LDHs for orthopedic disorders treatment are outlined and the corresponding state-of-the-art achievements are summarized for the first time. The potential of LDHs-based nanocomposites for extended therapeutics for bone diseases is highlighted and perspectives for LDHs-based scaffold design are proposed for facilitated clinical translation.

Performance analysis of avionics devices based on electro-thermal-stress multi-physics coupling under immersion cooling

The present study aims to analyze immersion cooling for the work reliability enhancement of avionics devices based on electro-thermal-stress multi-physics simulation. A comprehensive performance indicator considering the maximum DC IR-drop of the power supply network (PDN), the maximum temperature of the electronic elements and the maximum deformation of the printed circuit board (PCB) assembly is constructed to evaluate the effect of different flow distributor structure styles and Reynolds number (Re) on the work reliability of avionics devices. The results show that the maximum DC IR-drop of 2.0 V PDN was 73.83 mV which was the largest value among 1.5 V, 2.0 V, 3.3 V and 5.0 V PDN. The DC IR-drop of design A, design B and design C was smaller than the supply voltage fluctuation in a real design, this indicates that the flow distributor has no significant effect on enhancing the power delivery capability of PDN. The reflow in the middle part of design C makes the average temperature of PCB assembly lower than that of design A and design B by about 1–3 °C. The flow distributor has a significant effect on the maximum temperature of electronic elements and the pressure drop of avionics devices with Re increase, but not viable to decrease the maximum deformation of PCB assembly for design A and design B. The minimum of comprehensive evaluation function f is 0.038 when Re = 43,000 for design C, this means the comprehensive working reliability of the avionics server module is the best. Due to different flow patterns, the average temperature of PCB assembly for design C was lower which improve the electrical and mechanical properties, thus the value of f for design C was always smaller than that of design A and design B. The method and results herein revealed the advantages and potential limitations of immersion cooling on the working reliability of the avionics devices.

To understand the miglitol adsorption behavior on BC3, BN, and GNS nanosheets using DFT and QTAIM analysis for drug delivery applications

Utilizing nanomaterials in the drug delivery system has a potential impact on administering a drug to a patient’s body, and that helps to reduce the severe adverse effect by carrying them into the targeted cell location. The implementation of boron carbide (BC3), boron nitride (BN), and graphene nanosheet (GNS) as miglitol (MT) drug carriers in both gaseous and fluid phases has been evaluated using density functional theory. We methodically looked at the optimum adsorption energy, frontier molecular orbital, density of state, dipole moment, and UV–vis spectroscopy analysis to grasp the targeted drug delivery capability of these nanostructures. The adsorption energy analysis displayed that MT drug adsorption occurs stably on the nanosheet both in gas (−57.86 kj mol−1) and water (−43.72 kj mol−1) media. This physical interaction is suitable for an undeniable offloading of MT drugs to the targeted site. The outcomes of the quantum theory of atoms in molecules (QTAIM) have also supported these assessments. Our study reveals that the BC3 nanosheet exhibits more stable adsorption of MT drugs than that of BN and GNS.

Charge-Reduced Particles via Self-Propelled Electrohydrodynamic Atomization for Drug Delivery Applications.

Electrohydrodynamic atomization (EHDA) provides unparalleled control over the size and production rate of particles from solution. However, conventional methods produce highly charged particles that are not appropriate for inhalation drug delivery. We present a self-propelled EHDA system to address this challenge, a promising one-step platform for generating and delivering charge-reduced particles. Our approach uses a sharp electrode to produce ion wind, which reduces the cumulative charge in the particles and transports them to a target in front of the nozzle. We effectively controlled the morphologies of polymer products created from poly(vinylidene fluoride) (PVDF) at various concentrations. Our technique has also been proven safe for bioapplications, as evidenced by the delivery of PVDF particles onto breast cancer cells. The combination of simultaneous particle production and charge reduction, along with its direct delivery capability, makes the self-propelled EHDA a versatile technique for drug delivery applications.

Engineered extracellular vesicles as therapeutics of degenerative orthopedic diseases.

Degenerative orthopedic diseases, as a global public health problem, have made serious negative impact on patients' quality of life and socio-economic burden. Traditional treatments, including chemical drugs and surgical treatments, have obvious side effects and unsatisfactory efficacy. Therefore, biological therapy has become the focus of researches on degenerative orthopedic diseases. Extracellular vesicles (EVs), with superior properties of immunoregulatory, growth support, and drug delivery capabilities, have emerged as a new cell-free strategy for the treatment of many diseases, including degenerative orthopedic diseases. An increasing number of studies have shown that EVs can be engineered through cargo loading, surface modification, and chemical synthesis to improve efficiency, specificity, and safety. Herein, a comprehensive overview of recent advances in engineering strategies and applications of engineered EVs as well as related researches in degenerative orthopedic diseases, including osteoarthritis (OA), osteoporosis (OP), intervertebral disc degeneration (IDD) and osteonecrosis of the femoral head (ONFH), is provided. In addition, we analyze the potential and challenges of applying engineered EVs to clinical practice.

Intranasal administration of sodium nitroprusside augments antigen-specific mucosal and systemic antibody production in mice

The coronavirus disease 2019, i.e., the COVID-19 pandemic, caused by a highly virulent and transmissible pathogen, has profoundly impacted global society. One approach to combat infectious diseases caused by pathogenic microbes is using mucosal vaccines, which can induce antigen-specific immune responses at both the mucosal and systemic sites. Despite its potential, the clinical implementation of mucosal vaccination is hampered by the lack of safe and effective mucosal adjuvants. Therefore, developing safe and effective mucosal adjuvants is essential for the fight against infectious diseases and the widespread clinical use of mucosal vaccines. In this study, we demonstrated the potent mucosal adjuvant effects of intranasal administration of sodium nitroprusside (SNP), a known nitric oxide (NO) donor, in mice. The results showed that intranasal administration of ovalbumin (OVA) in combination with SNP induced the production of OVA-specific immunoglobulin A in the mucosa and increased serum immunoglobulin G1 levels, indicating a T helper-2 (Th2)-type immune response. However, an analog of SNP, sodium ferrocyanide, which does not generate NO, failed to show any adjuvant effects, suggesting the critical role of NO generation in activating an immune response. In addition, SNPs facilitated the delivery of antigens to the lamina propria, where antigen-presenting cells are located, when co-administered with antigens, and also transiently elicited the expression of interleukin-6, interleukin-1β, granulocyte colony-stimulating factor, C-X-C motif chemokine ligand 1, and C-X-C motif chemokine ligand 2 in nasal tissue. These result suggest that SNP is a dual-functional formulation with antigen delivery capabilities to the lamina propria and the capacity to activate innate immunity. In summary, these results demonstrate the ability of SNP to induce immune responses via an antigen-specific Th2-type response, making it a promising candidate for further development as a mucosal vaccine formulation against infectious diseases.