Delivery System Research Articles

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems.

Nucleic acid delivery requires vectorization for protection from nucleases, preventing clearance by the reticuloendothelial system, and targeting to allow cellular uptake. Nanovectors meeting the above specifications should be safe for the patient, simple to manufacture, and display long-term stability. Our nanovectors were obtained via the green process of polyelectrolyte complexation, carried out at 25 °C in water at a low shear rate using chitosan (a polycationic biocompatible polysaccharide of specific molar mass and acetylation degree) and dextran sulfate as a polyanionic biocompatible polysaccharide. These complexes formed nanoassemblies of primary nanoparticles (20-35 nm) and maintained their colloidal stability for over 1 year at 25 °C. They could be steam sterilized, and a model nucleic acid could be either encapsulated or surface adsorbed. A targeting agent was finally bound to their surface. This work serves as a proof of concept of the suitability of chitosan-based polyelectrolyte complexes as nanovectors by sequential multilayered adsorption of various biomacromolecules.

Cell Membrane-Derived Nanoparticles as Biomimetic Nanotherapeutics to Alleviate Fatty Liver Disease.

The prevalence of metabolic dysfunction associated-steatotic liver disease (MASLD) (formerly known as nonalcoholic fatty liver disease; NAFLD) is estimated at around 32% of the world's population, resulting in a major healthcare concern in recent times. Current pharmaceutical methods lack efficacy for the treatment of the disease because of suboptimal pharmacokinetic parameters including poor bioavailability, short half-life, and premature clearance. Designing an efficient drug delivery system that provides a protective environment is critical for addressing these challenges. Such a system should aim to enhance the cellular uptake of drugs, improve their bioavailability, and reduce the chances of rapid clearance. Here, we developed nanoengineered natural cell membrane-derived nanoparticles (CMNs) incorporated with a model drug, rosuvastatin, in the bilayer assembly of CMNs to reduce the accumulation of lipids in hepatocytes, a hallmark of MASLD. We used a cell extrusion technique to develop self-assembled CMNs with precise size control compared to the cell shearing method. Interestingly, the prepared CMNs were found to be nonphagocytic, representing around 1.13% of phosphatidylserine receptors on healthy cells, which allows the possibility of their use as stealth nanoparticles for drug delivery. Furthermore, CMNs exhibit higher drug-loading efficiency, excellent cytocompatibility, and enhanced cellular internalization capabilities. Moreover, we show that the delivery of rosuvastatin-loaded CMNs in the in vitro MASLD model efficiently reduced hepatocyte lipid accumulation, including total cholesterol (26.8 ± 3.1%) and triglycerides (11.8 ± 0.8%), compared to the negative control. Taken together, the nanoengineered biomimetic CMNs enhance the drug's bioactivity in hepatic cells, establishing a foundation for further investigation of this drug delivery system in treating MASLD.

Recent advances in sialic acid-based active targeting chemoimmunotherapy promoting tumor shedding: a systematic review.

Tumors have always been a major public health concern worldwide, and attempts to look for effective treatments have never ceased. Sialic acid is known to be a crucial element for tumor development and its receptors are highly expressed on tumor-associated immune cells, which perform significant roles in establishing the immunosuppressive tumor microenvironment and further boosting tumorigenesis, progression, and metastasis. Obviously, it is essential to consider sophisticated crosstalk between tumors, the immune system, and preparations, and understand the links between pharmaceutics and immunology. Sialic acid-based chemoimmunotherapy enables active targeting drug delivery via mediating the recognition between the sialic acid-modified nano-drug delivery system represented by liposomes and sialic acid-binding receptors on tumor-associated immune cells, which inhibit their activity and utilize their homing ability to deliver drugs. Such a "Trojan horse" strategy has remarkably improved the shortcomings of traditional passive targeting treatments, unexpectedly promoted tumor shedding, and persistently induced robust immunological memory, thus highlighting its prospective application potential for targeting various tumors. Herein, we review recent advances in sialic acid-based active targeting chemoimmunotherapy to promote tumor shedding, summarize the current viewpoints on the tumor shedding mechanism, especially the formation of durable immunological memory, and analyze the challenges and opportunities of this attractive approach.

Exploitation of functionalized green nanomaterials for plant disease management.

A crucial determining factor in agricultural productivity is biotic stress. In addition, supply of quality food to the ever-increasing world's population has raised the food demand tremendously. Therefore, enhanced agricultural crop productivity is the only option to mitigate these concerns. It ultimately demanded the often and indiscriminate use of synthetic agrochemicals such as chemical fertilizers, pesticides, insecticides, herbicides, etc. for the management of various biotic stresses including a variety of plant pathogens. However, the food chain and biosphere are severely impacted due to the use of such harmful agrochemicals and their byproducts. Hence, it is need of hour to search for novel, effective and ecofriendly approaches for the management of biotic stresses in crop plants. Particularly, in plant disease management, efforts are being made to take advantage of newly emerged science i.e. nanotechnology for the creation of inorganic nanoparticles (NPs) such as metallic, oxide, sulphide, etc. through different routes and their application in plant disease management. Among these, green nanomaterials which are synthesized using environmentally friendly methods and materials reported to possess unique properties (such as high surface area, adjustable size and shape, and specific functionalities) making them ideal candidates for targeted disease control. Nanotechnology can stop crop losses by managing specific diseases from soil, plants, and hydroponic systems. This review mainly focuses on the application of biologically produced green NPs in the treatment of plant diseases caused due to bacteria, viruses, and fungi. The utilization of green synthesis of NPs in the creation of intelligent targeted pesticide and biomolecule control delivery systems, for disease management is considered environmentally friendly due to its pursuit of less hazardous, sustainable, and environmentally friendly methods.

The Role of Engineering Ethics in Mitigating Corruption in Infrastructure Systems Delivery.

Indications that corruption mitigation in infrastructure systems delivery can be effective are found in the literature. However, there is an untapped opportunity to further enhance the efficacy of existing corruption mitigation strategies by placing them explicitly within the larger context of engineering ethics, and relevant policy statements, guidelines, codes and manuals published by international organizations. An effective matching of these formal statements on ethics to infrastructure systems delivery facilitates the identification of potential corruption hotspots and thus help establish or strengthen institutional mechanisms that address corruption. This paper reviews professional codes of ethics, and relevant literature on corruption mitigation in the context of civil engineering infrastructure development, as a platform for building a structure that connects ethical tenets and the mitigation strategies. The paper assesses corruption mitigation strategies against the background of the fundamental canons of practice in civil engineering ethical codes. As such, the paper's assessment is grounded in the civil engineer's ethical responsibilities (to society, the profession, and peers) and principles (such as safety, health, welfare, respect, and honesty) that are common to professional codes of ethics in engineering practice. Addressing corruption in infrastructure development continues to be imperative for national economic and social development, and such exigency is underscored by the sheer scale of investments in infrastructure development in any country and the billions of dollars lost annually through corruption and fraud.

Surface-Engineered Polygonatum Sibiricum Polysaccharide CaCO3 Microparticles as Novel Vaccine Adjuvants to Enhance Immune Response.

Micro- and nanoparticles delivery systems have been widely studied as vaccine adjuvants to enhance immunogenicity and sustain long-term immune responses. Polygonatum sibiricum polysaccharide (PSP) has been widely studied as an immunoregulator in improving immune responses. In this study, we synthesized and characterized cationic modified calcium carbonate (CaCO3) microparticles loaded with PSP (PEI-PSP-CaCO3, CTAB-PSP-CaCO3), studied the immune responses elicited by PEI-PSP-CaCO3 and CTAB-PSP-CaCO3 carrying ovalbumin (OVA). Our results demonstrated that PEI-PSP-CaCO3 significantly enhanced the secretion of IgG and cytokines (IL-4, IL-6, IFN-γ, and TNF-α) in vaccinated mice. Additionally, PEI-PSP-CaCO3 induced the activation of dendritic cells (DCs), T cells, and germinal center (GC) B cells in draining lymph nodes (dLNs). It also enhanced lymphocyte proliferation, increased the ratio of CD4+/CD8+ T cells, and elevated the frequency of CD3+ CD69+ T cells in spleen lymphocytes. Therefore, PEI-PSP-CaCO3 microparticles induced a stronger cellular and humoral immune response and could be potentially useful as a vaccine delivery and adjuvant system.

Nanoparticle-Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia-Reperfusion Injury.

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia-reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle-patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle-patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle-patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.

Primary Care Telemedicine and Care Continuity: Implications for Timeliness and Short-term Follow-up Healthcare.

The effectiveness of telemedicine by a patient's own primary care provider (PCP) versus another available PCP is understudied. Examine the association between primary care visit modality with timeliness and follow-up in-person healthcare, including variation by visits with the patient's own PCP versus another PCP. Cohort study including primary care visits in a large, integrated delivery system in 2022. Outcomes included timeliness (visit completed within 7days of scheduling) and in-person follow-up (PCP visits, emergency department (ED) visits, hospitalizations) within 7days of the index PCP visit. Logistic regression measured the association between visit modality (in-person, video, and audio-only telemedicine) with the patient's own PCP or another PCP and outcomes, adjusting for characteristics. Among 4,817,317 primary care visits, 59% were in-person, 27% audio-only, and 14% video telemedicine. Most (71.3%) were with the patient's own PCP. Telemedicine visits were timelier, with modality having a larger association for visits with patient's own PCP versus another PCP (P < 0.001). For visits with patient's own PCPs, return office visit rates were 1.2% for in-person, 5.3% for video, and 6.1% for audio-only. For another PCP, rates were 2.2% for in-person, 7.3% for video, and 8.1% for audio. Follow-up ED visits ranged from 1.4% (in-person) to 1.6% (audio-only) with own PCP, compared to 1.9% (in-person) to 2.3% (audio-only) with another PCP. Differences in return office and ED visits between in-person and telemedicine were larger for visits with another PCP compared to their own PCP (P < 0.001). Follow-up hospitalizations were rare, ranging from 0.19% (in-person with own PCP) to 0.32% (video with another PCP). Differences in return office and ED visits between in-person and telemedicine were larger when patients saw a less familiar PCP compared to their own PCP, reinforcing the importance of care continuity.

The San Francisco Health Systems Collaborative: Public Health and Health Care Delivery Systems’ Response to the Covid-19 Pandemic

The San Francisco Health Systems Collaborative: Public Health and Health Care Delivery Systems’ Response to the Covid-19 Pandemic

Nanomotor-hydrogel Delivery System with Enhanced Antibacterial Performance for Wound Treatment.

In this study, we present a novel system consisting of nanomotors and a hydrogel. Calcium carbonate nanomotors are prepared using layer-by-layer self-assembly technology with calcium carbonate nanoparticles as the core and catalase (CAT) and polydopamine (PDA) as the shell. Calcium carbonate nanomotors were loaded into a Schiff base hydrogel to synthesize the CaCO3@NM-hydrogel system. A nanomotor is a device that works on the nanoscale to convert some form of energy to mechanical energy. The motion speed of the system in 5.0 mM H2O2 aqueous solution under near-infrared light (NIR) irradiation with a power density of 1.8 W/cm2 is 13.6 μm/s. The addition of CaCO3@NM further promotes gelation and improves the mechanical properties. The energy storage modulus increases to 4.0 × 103 Pa, which is 50 times higher. Schiff base hydrogels form dynamic reversible chemical bonds due to inter- and intramolecular hydrogen bonding. They also have good self-healing properties, as observed by measuring the energy storage modulus versus the loss modulus at 1 versus 10 kHz. The results show that the system significantly inhibited the growth of both Gram-positive bacteria, Staphylococcus aureus, and Gram-negative bacteria, Escherichia coli, after 48 h, with an inhibition rate of nearly 95%. These findings provide a basis for further research and potential applications of the system in wound dressings.

Spatial Organization of Lipid Nanoparticle siRNA Delivery Systems Revealed by an Integrated Magnetic Resonance Approach.

Lipid nanoparticles (LNPs) are increasingly finding applications in targeted drug delivery, including for subcutaneous, intravenous, inhalation, and vaccine administration. While a variety of microscopy techniques are widely used for LNP characterization, their resolution does not allow for characterization of the spatial organization of different components, such as the excipients, targeting agents, or even the active ingredient. Herein, an approach is presented to probe the spatial organization of individual constituent groups of LNPs used for siRNA-based drug delivery, currently in clinical trials, by multinuclear solid-state magic-angle-spinning nuclear magnetic resonance (MAS NMR) spectroscopy. Dynamic nuclear polarization is exploited (DNP) for sensitivity enhancement, together with judicious 2H labeing, to detect functionally important LNP constituents, the siRNA and the targeting agent (<1-2 w/v%), respectively, and achieve a structural model of the LNP locating the siRNA in the core, the targeting agent below the surface, and the sugars above the lipid bilayer at the surface. The integrated approach presented here is applicable for structural analysis of LNPs and can be extended more generally to other multi-component biological formulations.

Gamma-Irradiated Gum Arabic Grafted with 2-Hydroxyethyl Methacrylate: A Novel Superabsorbent Polymer for Controlled Folic Acid Release.

This study explores the synthesis and characterization of superabsorbent hydrogels derived from chemically modified gum Arabic, designed for controlled folic acid release. The synthesis involves a two-step process: carboxymethylation followed by grafting with 2-hydroxyethyl methacrylate via gamma irradiation. The resulting hydrogels exhibit enhanced mechanical strength and controlled diffusivity, essential for nutrient delivery systems. Key factors such as copolymer composition and irradiation dose are investigated, affecting the synthesis process. Systematic studies of swelling behaviors reveal that the hydrogel achieves a maximum swelling of 888.1% at 40°C. The hydrogels are loaded with folic acid, and in vitro, sustained release profiles are examined under various pH conditions. The maximum release of 83.3% is observed after 24h at pH 7.0, following a Korsmeyer-Peppas release mechanism. Different characterization techniques, confirm the successful synthesis and unique properties of the superabsorbent hydrogels. Rheological behavior analysis, scanning electron microscopy, and biocompatibility assessments provide a comprehensive understanding of the hydrogel structures. Gamma irradiation ensures a homogeneous network structure, crucial for optimal swelling behavior and mechanical properties. This research highlights the potential of eco-friendly biopolymer hydrogels in precise drug delivery applications, leveraging the safety and process control benefits of gamma irradiation.

Bio-Nano Synergy in Therapeutic Applications: Drug-Graphene Oxide Nanocomposites for Modulated Acetylcholinesterase Inhibition and Radical Scavenging.

The current study explores the synergistic application of biophysical chemistry and nanotechnology in therapeutic treatments, focusing specifically on the development of advanced biomaterials to repurpose FDA-approved Alzheimer's disease (AD) drugs as potent antioxidants. By integration of AD drugs into graphene oxide (GO) nanocomposites, an attempt to enhance the acetylcholinesterase (AChE) inhibition and increase radical scavenging activity is proposed. This bionano synergy is designed to leverage the unique properties of both the nanomaterial surface and the bioactive compounds, improving treatment effectiveness. The nanocomposites also promise targeted drug delivery, as GO can traverse the blood-brain barrier to inhibit AChE more effectively in AD patients. Furthermore, the drug-GO nanocomposite exhibits enhanced radical scavenging capabilities, offering additional therapeutic benefits. This study also elucidates a molecular level understanding on how the properties of the drugs are modified when integrated into nanocomposites with GO, enabling the development of more effective materials. The interdisciplinary approach presented in this study exploits the potential of nanotechnology to enhance drug delivery systems and achieve superior therapeutic outcomes through bionano synergy.

Deep Learning for the Accurate Prediction of Triggered Drug Delivery.

The need to mitigate the adverse effects of chemotherapy has driven the exploration of innovative drug delivery approaches. One emerging trend in cancer treatment is the utilization of Drug Delivery Systems (DDSs), facilitated by nanotechnology. Nanoparticles, ranging from 1 nm to 1000 nm, act as carriers for chemotherapeutic agents, enabling precise drug delivery. The triggered release of these agents is vital for advancing this novel drug delivery system. Our research investigated this multifaceted delivery capability using liposomes and metal organic frameworks as nanocarriers and utilizing all three targeting techniques: passive, active, and triggered. Liposomes are modified using targeting ligands to render them more targeted toward certain cancers. Moieties are conjugated to the surfaces of these nanocarriers to allow for their binding to receptors overexpressed on cancer cells, thus increasing the accumulation of the agent at the tumor site. A novel class of nanocarriers, namely metal organic frameworks, has emerged, showing promise in cancer treatment. Triggering techniques (both intrinsic and extrinsic) can be used to release therapeutic agents from nanoparticles, thus enhancing the efficacy of drug delivery. In this study, we develop a predictive model combining experimental measurements with deep learning techniques. The model accurately predicts drug release from liposomes and MOFs under various conditions, including low- and high-frequency ultrasound (extrinsic triggering), microwave exposure (extrinsic triggering), ultraviolet light exposure (extrinsic triggering), and different pH levels (intrinsic triggering). The deep learning-based predictions significantly outperform linear predictions, proving the utility of advanced computational methods in drug delivery. Our findings demonstrate the potential of these nanocarriers and highlight the efficacy of deep learning models in predicting drug release behavior, paving the way for enhanced cancer treatment strategies.

Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection

Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein and a viable target for cardioprotection against myocardial ischaemia-reperfusion injury. Here, we reported a novel Drp1 inhibitor (DRP1i1), delivered using a cardiac-targeted nanoparticle drug delivery system, as a more effective approach for achieving acute cardioprotection. DRP1i1 was encapsulated in cubosome nanoparticles with conjugated cardiac-homing peptides (NanoDRP1i1) and the encapsulation efficiency was 99.3 ± 0.1 %. In vivo, following acute myocardial ischaemia-reperfusion injury in mice, NanoDRP1i1 significantly reduced infarct size and serine-616 phosphorylation of Drp1, and restored cardiomyocyte mitochondrial size to that of sham group. Imaging by mass spectrometry revealed higher accumulation of DRP1i1 in the heart tissue when delivered as NanoDRP1i1. In human cardiac organoids subjected to simulated ischaemia-reperfusion injury, treatment with NanoDRP1i1 at reperfusion significantly reduced cardiac cell death, contractile dysfunction, and mitochondrial superoxide levels. Following NanoDRP1i1 treatment, cardiac organoid proteomics further confirmed reprogramming of contractile dysfunction markers and enrichment of the mitochondrial protein network, cytoskeletal and metabolic regulation networks when compared to the simulated injury group. These proteins included known cardioprotective regulators identified in human organoids and in vivo murine studies following ischaemia-reperfusion injury. DRP1i1 is a promising tool compound to study Drp1-mediated mitochondrial fission and exhibits promising therapeutic potential for acute cardioprotection, especially when delivered using the cardiac-targeted cubosome nanoparticles.

A fluid–particle decomposition approach to matching market design for crowdsourced delivery systems

This paper considers a crowdsourced delivery (CSD) system that effectively utilizes the existing trips to fulfill parcel delivery as a matching problem between CSD drivers and delivery tasks. This matching problem has two major challenges. First, it is a large-scale combinatorial optimization problem that is hard to solve in a reasonable computational time. Second, the evaluation of the objective function for socially optimal matching contains the utility of drivers for performing the tasks, which is generally unobservable private information. To address these challenges, this paper proposes a hierarchical distribution mechanism of CSD tasks that decomposes the matching problem into the task partition (master problem) and individual task-driver matching within smaller groups of drivers (sub-problems). We incorporate an auction mechanism with truth-telling and efficiency into the sub-problems so that the drivers’ perceived utilities are revealed through their bids. Furthermore, we formulate the master problem as a fluid model based on continuously approximated decision variables. By exploiting the random utility framework, we analytically represent the objective function of the problem using continuous variables, without explicitly knowing the drivers’ utilities. The numerical experiment shows that the proposed approach solved large-scale matching problems at least 100 times faster than a naive LP solver and approximated the original objective value with errors of less than 1%. The code of this work is available at https://github.com/yuki-oyama/fluid-particle-csd.

Toxicological Analysis of Nanoparticles and Microparticles Used as Oral Vaccine Delivery Systems using Vero Cell

Background: The present study was carried out to evaluate in-vitro toxicity associated with chitosan nanoparticles, Gantrez® nanoparticles and poly-lactide co-glycolide (PLG) microparticle in Vero cell line. The cytotoxicity of all three micro/nano-particles was assessed using different concentration. Methods: For each concentration of these delivery systems, the confluent monolayer of Vero cells was treated for a period of 48 hours and studied for morphological alteration and cell survivability after the treatment. Results: It was observed that the different concentrations of chitosan nanoparticles and Gantrez® nanoparticles did not have significant effect on the cell viability as evident from the non-significant difference between the OD540 of formazan product formed from MTT in treated and untreated cells. The concentration of chitosan nanoparticles and Gantrez® nanoparticles up to 1000 µg/ml did not have any influence in cellular metabolic activities and viability. However, a slight reduction (statistically insignificant) in the cellular viability and metabolic activities were observed when PLG microparticles were used at 1000 µg/ml.

Advancements in nanomedicine delivery systems: unraveling immune regulation strategies for tumor immunotherapy.

This review highlights the significant role of nanodrug delivery systems (NDDS) in enhancing the efficacy of tumor immunotherapy. Focusing on the integration of NDDS with immune regulation strategies, it explores their transformative impacts on the tumor microenvironment and immune response dynamics. Key advancements include the optimization of drug delivery through NDDS, targeting mechanisms like immune checkpoint blockade and modulating the immunosuppressive tumor environment. Despite the progress, challenges such as limited clinical efficacy and complex manufacturing processes persist. The review emphasizes the need for further research to optimize these systems, potentially revolutionizing cancer treatment by improving delivery efficiency, reducing toxicity and overcoming immune resistance.

The Impact of Increased PEEP on Hemodynamics, Respiratory Mechanics, and Oxygenation in Pediatric ARDS.

PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS. Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected. A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8-12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O). Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.

Biocompatible PAMAM-PLGA-PCL Nanocarrier for Efficient Curcumin Delivery to Lung Cancer Cells: In Vitro Studies.

We developed a novel polylactic-co-glycolic acid (PLGA)-polyamidoamine G4 (PAMAM G4)-polycaprolactone (PCL) nanocarrier for efficient delivery of curcumin (Cur) to A549 lung cancer cells. The synthesized nanocarrier was characterized by applying analytical techniques, FT-IR, DLS, TEM, and TGA. Successful synthesis, nano-size diameter (40 to 80 nm), near neutral surface charge (8.0 mV), and high drug entrapment (11.5%) were measured for the nanocarrier. Controlled (about 5 folds within first 2 h) and pH-sensitive (2 to 3 folds faster within first hours) Cur release observed for PLGA-PAMAM-PCL-Cur. Cell viability test (MTT assay) indicated the high capability of nanocarrier in suppression of A549 cancer cells (21% viability after 24 h of treatment with 200 nM) while did not result in toxicity on MSC normal cells. The IC50 observed for 50 nM at 24 h of post-treatment in A549 cells. The qRT-PCR technique indicated inducing the expression of apoptotic genes (Caspase9 and Bax) by 6-8 folds and suppressing anti-apoptotic gene (Bcl2) by 7 folds. ROS considerably increased in cancer cells as well. This nanocarrier would be a promising drug delivery system against lung cancer.