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At least 1,747 records · Page 97
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

Temporal breakdown and Borel resummation in the complex Langevin method

We reexamine the Parisi-Klauder conjecture for complex e{sup i{theta}/2}{phi}{sup 4} measures with a Wick rotation angle 0{<=}{theta}/2{<=}{pi}/2 interpolating between Euclidean signature and Lorentzian signature. Our main result is that the asymptotics for short stochastic times t encapsulates information also about the equilibrium aspects. The moments evaluated with the complex measure and with the real measure defined by the stochastic Langevin equation have the same t{yields}0 asymptotic expansion which is shown to be Borel summable. The Borel transform correctly reproduces the time dependent moments of the complex measure for all t, including their t{yields}{infinity} equilibrium values. On the other hand the results of a direct numerical simulation of the Langevin moments are found to disagree from the 'correct' result for t larger than a finite t{sub c}. The breakdown time t{sub c} increases powerlike for decreasing strength of the noise's imaginary part but cannot be excluded to be finite for purely real noise. To ascertain the discrepancy we also compute the real equilibrium distribution for complex noise explicitly and verify that its moments differ from those obtained with the complex measure. - Highlights: Black-Right-Pointing-Pointer The Parisi-Klauder conjecture is reexamined for complex e{sup i{theta}/2}{phi}{sup 4} measures. Black-Right-Pointing-Pointer The time dependent moments are evaluated by temporal Borel resummation. Black-Right-Pointing-Pointer The results disagree with the Langevin simulations beyond a critical time t{sub c}. Black-Right-Pointing-Pointer t{sub c} increases with decreasing strength of the noise's imaginary part. Black-Right-Pointing-Pointer The technical reason for the breakdown is identified.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2015

Photo-synthesis of protein-based nanoparticles and the application in drug delivery

Recently, protein-based nanoparticles as drug delivery systems have attracted great interests due to the excellent behavior of high biocompatibility and biodegradability, and low toxicity. However, the synthesis techniques are generally costly, chemical reagents introduced, and especially present difficulties in producing homogeneous monodispersed nanoparticles. Here, we introduce a novel physical method to synthesize protein nanoparticles which can be accomplished under physiological condition only through ultraviolet (UV) illumination. By accurately adjusting the intensity and illumination time of UV light, disulfide bonds in proteins can be selectively reduced and the subsequent self-assembly process can be well controlled. Importantly, the co-assembly can also be dominated when the proteins mixed with either anti-cancer drugs, siRNA, or active targeting molecules. Both in vitro and in vivo experiments indicate that our synthesized protein–drug nanoparticles (drug-loading content and encapsulation efficiency being ca. 8.2% and 70%, respectively) not only possess the capability of traditional drug delivery systems (DDS), but also have a greater drug delivery efficiency to the tumor sites and a better inhibition of tumor growth (only 35% of volume comparing to the natural growing state), indicating it being a novel drug delivery system in tumor therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Stability of anisotropic stellar filaments

The study of perturbation of self-gravitating celestial cylindrical object have been carried out in this paper. We have designed a framework to construct the collapse equation by formulating the modified field equations with the background of f(R,T) theory as well as dynamical equations from the contracted form of Bianchi identities with anisotropic matter configuration. We have encapsulated the radial perturbations on metric and material variables of the geometry with some known static profile at Newtonian and post-Newtonian regimes. We examined a strong dependence of unstable regions on stiffness parameter which measures the rigidity of the fluid. Also, the static profile and matter variables with f(R,T) dark source terms control the instability of compact cylindrical system.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2021

Structure sensitivity and its effect on methane turnover and carbon co-product selectivity in thermocatalytic decomposition of methane over supported Ni catalysts

We explore how thermocatalytic decomposition of methane (TCD) is a promising approach for producing CO 2 -free hydrogen and solid carbon co-product. In this study, a series of Al 2 O 3 - and MgAl 2 O 4 -based Ni catalysts, prepared with varying synthesis and pretreatment methods, were evaluated for methane TCD performance at 650°C and characterized before and after reaction to elucidate activity-structure relationships. We found that methane TCD turnover increases with Ni particle size. Further, large Ni particle sizes (i.e., >20 nm) are selective toward the formation of carbon nanotubes (CNTs), while small Ni particle sizes (i.e., <10 nm) are selective toward the formation of graphitic carbon layers. The formation of graphitic carbon layers block access to Ni active sites, thus rendering the catalyst inactive more quickly than when CNTs are produced. Additionally, the catalyst deactivation observed with time-on-stream is due to the fragmentation of Ni particles into smaller Ni particles followed by their encapsulation with graphitic carbon layers.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Mechanistic in situ insights into the formation, structural and catalytic aspects of the La 2 NiO 4 intermediate phase in the dry reforming of methane over Ni-based perovskite catalysts

In this work, we focus on the stability and bulk/surface structural properties of the Ruddlesden-Popper phase La 2 NiO 4 and their consequences for dry reforming of methane (DRM) activity. Fuelled by the appearance as a crucial intermediate during in situ decomposition of highly DRM-active LaNiO3 perovskite structures, we show that La 2 NiO 4 can be equally in situ decomposed into a Ni/La 2 O 3 phase offering CO 2 capture and release necessary for DRM activity, albeit at much higher temperatures compared to LaNiO 3 . Decomposition in hydrogen also leads to an active Ni/La 2 O 3 phase. In situ X-ray diffraction during DRM operation reveals considerable coking and encapsulation of exsolved Ni, yielding much smaller Ni crystallites compared to on LaNiO 3 , where coking is virtually absent. Additionally, generalizing the importance of intermediate Ruddlesden-Popper phases, the in situ decomposition of La-based perovskite structures yields several obstacles due to the high stability of both the parent perovskite and the Ruddlesden-Popper structures and the occurrence of parasitic structures.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Grafted nickel-promoter catalysts for dry reforming of methane identified through high-throughput experimentation

High-throughput synthesis of a series of monometallic and bimetallic catalysts (45 bimetallic and 50 monometallic samples) consisting of nickel and one of nine different metal promoters (B, Co, Cu, Fe, Mg, Mn, Sn, V and Zn) supported on one of six different metal oxides alumina, ceria, magnesia, silica and titania) is carried out via organometallic grafting using a robotic platform. The catalysts are evaluated for their activity and selectivity for the dry reforming of methane at a feed ratio of CH 4 :CO 2 of 1 at 650–800 °C in a parallel flow reactor system. The type of oxide support prevails over the type of additive for both catalyst activity and stability. On Al 2 O 3 and MgO, Fe was found to be the best promoter; on SiO 2 , Cu is the best promoter at 700 °C and higher, while on TiO 2 , Mn is found to enhance the conversion at 800 °C. On CeO 2 , all additives except Fe have beneficial effects. Twenty-five catalysts show > 90% methane conversion with ten catalysts showing > 95% conversion at 800 °C with the H 2 :CO ratios ranging from 0.8 to 1.2. Amongst the ten highest performers, NiFe/Al 2 O 3 and NiFe/MgO are more active than Ni/Al 2 O 3 and Ni/MgO, respectively and were stable over a period of 25 h at 800 °C. Characterization on the as-prepared samples reveals highly dispersed phase, while after reduction in H 2 , highly dispersed and reduced nickel particles up to 10 nm are formed. The particles do not increase in size under dry reforming reaction conditions at 800 °C. An increased hydrogen consumption observed during H 2 -TPR of the nickel particles is positively correlated with methane conversion for Al 2 O 3 -based catalysts. The resistance to deactivation by coking and variation in coke structure are investigated by spectroscopic and microscopic methods to identify the relationship between metal promoters, alloy formation, and type of surface carbon deposits. Carbon whiskers were observed on the ten selected spent samples and are preferentially deposited on Ni rather than on the promoters. Carbon nanotube formation and metal particle removal from support were not observed to cause deactivation while amorphous carbon formation was clearly linked to catalyst deactivation, as amorphous carbon could encapsulate nickel, either on the support or at the end of the carbon nanotube. Furthermore, the organometallic grafting technique is an efficient and suitable technique for synthesizing highly dispersed and homogeneous phases which lead to high conversion and high durability for dry reforming of methane.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

Combined experimental and numerical evaluation of a prototype nano-PCM enhanced wallboard

In the United States, forty-eight (48) percent of the residential end-use energy consumption is spent on space heating and air conditioning. Reducing envelope-generated heating and cooling loads through application of phase change material (PCM)-enhanced building envelopes can facilitate maximizing the energy efficiency of buildings. Combined experimental testing and numerical modeling of PCM-enhanced envelope components are two important aspects of the evaluation of their energy benefits. An innovative phase change material (nano-PCM) was developed with PCM encapsulated with expanded graphite (interconnected) nanosheets, which is highly conductive for enhanced thermal storage and energy distribution, and is shape-stable for convenient incorporation into lightweight building components. A wall with cellulose cavity insulation and prototype PCM-enhanced interior wallboards was built and tested in a natural exposure test (NET) facility in a hot-humid climate location. The test wall contained PCM wallboards and regular gypsum wallboard, for a side-by-side annual comparison study. Further, numerical modeling of the walls containing the nano-PCM wallboard was performed to determine its actual impact on wall-generated heating and cooling loads. The model was first validated using experimental data, and then used for annual simulations using Typical Meteorological Year (TMY3) weather data. This article presents the measured performance and numerical analysis evaluating the energy-saving potential of the nano-PCM-enhanced wallboard.

finite element analysis↗
DOE OSTI2020

Reinforcement learning based automated history matching for improved hydrocarbon production forecast

History matching aims to find a numerical reservoir model that can be used to predict the reservoir performance. An engineer and model calibration (data inversion) method are required to adjust various parameters/properties of the numerical model in order to match the reservoir production history. In this study, we develop deep neural networks within the reinforcement learning framework to achieve automated history matching that will reduce engineers’ efforts, human bias, automatically and intelligently explore the parameter space, and remove the need of large set of labeled training data. To that end, a fast-marching-based reservoir simulator is encapsulated as an environment for the proposed reinforcement learning. The deep neural-network-based learning agent interacts with the reservoir simulator within reinforcement learning framework to achieve the automated history matching. Reinforcement learning techniques, such as discrete Deep Q Network and continuous Deep Deterministic Policy Gradients, are used toth, used to train the learning agents. The continuous actions enable the Deep Deterministic Policy Gradients to explore more states at each iteration in a a learning episode; consequently, a better history matching is achieved using this algorithm as compared to Deep Q Network. For simplified dual-target composite reservoir models, the best history-matching performances of the discrete and continuous learning methods in terms of normalized root mean square errors are 0.0447 and 0.0038, respectively. Furthermore, our study shows that continuous action space achieved by the deep deterministic policy gradient drastically outperforms deep Q network.

42 ENGINEERING↗
DOE OSTI2021

Design and performance evaluation of a dual-circuit thermal energy storage module for air conditioners

We present experimental results and a validated numerical model of a dual-circuit phase-change thermal energy storage module for air conditioners. The module incorporates a phase-change material encapsulated in compressed expanded natural graphite foam. We used n-tetradecane as the PCM with a transition temperature (~4.5 °C) suitable for air-conditioning applications. Heat exchange to and from the module is accomplished through two fluid loops operating as a heat source and sink embedded inside multiple slabs of the composite material. This dual-circuit design enables easier integration with air-conditioning equipment and provides enhanced flexibility in system operation as compared to the state-of-the-art thermal storage systems. When integrated with an air-conditioner, this design will enable peak-load shaving and enhances operational efficiency. The thermal storage device was designed for a nominal storage capacity of ~ 3.5 kWh. We evaluated the heat transfer and energy storage performance of this device using standalone heat transfer experiments to estimate key thermal resistances and identify design improvements before integration with an air conditioner. The numerical model of the heat exchanger uses a combination of discretized and lumped parameter approaches to maintain a balance between accuracy and computational expense. Our analyses show that the geometric features and integration of fluid tubes are key contributors to the thermal contact resistance between the fluid and the thermal storage material, and consequently, to the overall performance of the thermal storage module. Our standalone experiments also identified important operating scenarios in which this thermal storage module can be used for air-conditioning in buildings.

25 ENERGY STORAGE↗
DOE OSTI2020

Characterization of 244 Cm Neutron Sources

There is a need to find a replacement for the 252 Cf sources currently used in Standards-based performance testing of neutron instrumentation. This is a result of its relatively short half-life, concerns about future availability and recent increases in cost. A potential replacement source, 244 Cm is evaluated in this study where two commercially available sources have been acquired and their neutron emission spectra measured using a pair of spectrometers. Both instruments showed the 244 Cm spontaneous neutron spectrum to be fully consistent with a MCNP6®-calculated spectrum using published Watt fission parameters for 244 Cm. In addition, the emission rate of the weaker 244 Cm source was established through a direct count rate comparison against a calibrated and similarly encapsulated 252 Cf source. The 244 Cm source emission rate was found to be in excellent agreement with value stated on the manufacturer's source certificate. It is concluded that 244 Cm would be an ideal replacement for 252 Cf based on its longer half-life (18.1 y) and its essentially identical neutron emission spectrum. In addition, 244 Cm sources are commercially available at reasonable cost.

244Cm↗
DOE OSTI2021

Germplasm cryopreservation of macroalgae for aquaculture breeding and natural resource conservation: A review

The expansion of the global macroalgal aquaculture and climate change creates the need for germplasm preservation of valuable aquaculture strains and maintenance of natural biodiversity. Compared to the large number of studies in fish and shellfish species, relative few studies have been conducted on the macroalgal germplasm cryopreservation. The first cryopreservation of macroalgae to –75 °C was reported on Neopyropia tenera (formerly called Porphyra tenera) in 1964. To date, a total of 34 studies reported germplasm cryopreservation in 33 species, including Chlorophyta (7 species), Ochrophyta (14 species), and Rhodophyta (12 species). Here, the goal of this review was to summarize the published studies on macroalgal germplasm cryopreservation, compare the reported protocols for the cryopreservation process, and identify the factors affecting post-thaw viability. Overall, macroalgal germplasm cryopreservation included haploid or diploid thalli, spores, and gametes. Cryotubes (1.5-ml or 2-ml) have been widely used to package germplasm samples for cooling and storage in most studies, and the 0.5-ml straws and 5-ml cryotubes have been used in several studies. Two approaches (programmable controlled cooling and vitrification) were employed for macroalgal germplasm cryopreservation. A two-step programmable controlled cooling (e.g., from initial culture temperature to a frozen temperature, such as –40 °C, and then directly plunging into liquid nitrogen at –196 °C) was determined to be an effective cooling strategy. Vitrification, a super rapid cooling for a sample to form non-crystalline amorphous solid, was applied on macroalgal germplasm cryopreservation with sample encapsulation and dehydration. Survival of post-thaw samples varied significantly in different studies. Based on research updates, recommendations are made for future research. It is expected that this review can serve as a foundation for future germplasm banking of macroalgae for aquaculture and biodiversity preservation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Prolonged effect of fluid flow stress on the proliferative activity of mesothelial cells after abrupt discontinuation of fluid streaming

Highlights: Black-Right-Pointing-Pointer Late-onset peritoneal fibrosis leading to EPS remains to be elucidated. Black-Right-Pointing-Pointer Fluid streaming is a potent factor for peritoneal fibrosis in PD. Black-Right-Pointing-Pointer We focused on the prolonged effect of fluid streaming on mesothelial cell kinetics. Black-Right-Pointing-Pointer A history of fluid streaming exposure promoted mesothelial proliferative activity. Black-Right-Pointing-Pointer We have thus identified a potent new factor for late-onset peritoneal fibrosis. -- Abstract: Encapsulating peritoneal sclerosis (EPS) often develops after transfer to hemodialysis and transplantation. Both termination of peritoneal dialysis (PD) and transplantation-related factors are risks implicated in post-PD development of EPS, but the precise mechanism of this late-onset peritoneal fibrosis remains to be elucidated. We previously demonstrated that fluid flow stress induced mesothelial proliferation and epithelial-mesenchymal transition via mitogen-activated protein kinase (MAPK) signaling. Therefore, we speculated that the prolonged bioactive effect of fluid flow stress may affect mesothelial cell kinetics after cessation of fluid streaming. To investigate how long mesothelial cells stay under the bioactive effect brought on by fluid flow stress after removal of the stress, we initially cultured mesothelial cells under fluid flow stress and then cultured the cells under static conditions. Mesothelial cells exposed to fluid flow stress for a certain time showed significantly high proliferative activity compared with static conditions after stoppage of fluid streaming. The expression levels of protein phosphatase 2A, which dephosphorylates MAPK, in mesothelial cells changed with time and showed a biphasic pattern that was dependent on the duration of exposure to fluid flow stress. There were no differences in the fluid flow stress-related bioactive effects on mesothelial cells once a certain time had passed. The present findings show that fluid flow stress exerts a prolonged bioactive effect on mesothelial cells after termination of fluid streaming. These findings support the hypothesis that a history of PD for a certain period could serve as a trigger of EPS after stoppage of PD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Bacteria-mediated in vivo delivery of quantum dots into solid tumor

Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

Nanoparticles are becoming promising carriers for gene delivery because of their high capacity in gene loading and low cell cytotoxicity. In this study, a chitosan-based nanoparticle encapsulated within a recombinant pcDNA3.1-dsNKG2D-IL-15 plasmid was generated. The fused dsNKG2D-IL-15 gene fragment consisted of double extracellular domains of NKG2D with IL-15 gene at downstream. The average diameter of the gene nanoparticles ranged from 200 nm to 400 nm, with mean zeta potential value of 53.8 ± 6.56 mV. The nanoparticles which were loaded with the dsNKG2D-IL-15 gene were uptaken by tumor cells with low cytotoxicity. Tumor cells pre-transfected by gene nanopartilces stimulated NK and T cells in vitro. Intramuscular injection of gene nanoparticles suppressed tumor growth and prolonged survival of tumor-bearing mice through activation of NK and CD8{sup +} T cells. Thus, chitosan-based nanoparticle delivery of dsNKG2D-IL-15 gene vaccine can be potentially used for tumor therapy. - Highlights: • Generation of a nanoparticle for delivery of dsNKG2D-IL-15 gene. • Characterization of the gene nanoparticle. • Antitumor activity mediated by the gene nanoparticle.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Mutational analysis of hepatitis B virus pre-S1 (9–24) fusogenic peptide

A hollow nanoparticle known as a bio-nanocapsule (BNC) consisting of hepatitis B virus (HBV) envelope L protein and liposome (LP) can encapsulate drugs and genes and thereby deliver them in vitro and in vivo to human hepatic tissues, specifically by utilizing the HBV-derived infection machinery. Recently, we identified a low pH-dependent fusogenic domain at the N-terminal part of the pre-S1 region of the HBV L protein (amino acid residues 9 to 24; NPLGFFPDHQLDPAFG), which shows membrane destabilizing activity (i.e., membrane fusion, membrane disruption, and payload release) upon interaction with target LPs. In this study, instead of BNC and HBV, we generated LPs displaying a mutated form of the pre-S1 (9–24) peptide, and performed a membrane disruption assay using target LPs containing pyranine (fluorophore) and p-xylene-bis (N-pyridinium bromide) (DPX) as a quencher. The membrane disruption activity was found to correlate with the hydrophobicity of the whole structure, while the peptide retained a random-coil structure even under low pH condition. One large hydrophobic cluster (I) and one small hydrophobic cluster (II) residing in the peptide would be connected by the protonation of residues D16 and D20, and thereby exhibit strong membrane disruption activity in a low pH-dependent manner. Furthermore, the introduction of a positively charged residue enhanced the activity significantly, suggesting that a sole positively charged residue (H17) may be important for the interaction with target LPs by electrostatic interaction. Collectively, these results suggest that the pre-S1 (9–24) peptide may be involved in the endosomal escape of the BNC's payloads, as well as in the HBV uncoating process. -- Highlights: •Low pH-dependent fusogenic domain of hepatitis B virus pre-S1 region is analyzed. •The domain resides in pre-S1 (9–24) region, exhibiting random-coil structure. •Membrane disruption activity of the domain is mainly driven by its hydrophobicity. •Two Asp residues of the domain function as low-pH sensing molecule.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Macrophage infiltration regulates the adipose ECM reconstruction and the fibrosis process after fat grafting

Background: Fat grafting experiences a regeneration process from free lipoaspirate to intact adipose tissue. The adipose extracellular matrixes (ECM) provide the structure and biochemical support for surrounding cells; inflammatory cells, like macrophages, regulate the process. Our hypothesis states that transferred fat undergoes ECM remodeling after fat grafting and this process is regulated by macrophage infiltration. Methods: Lipoaspirate was injected subcutaneously into the back of nude mice. The micro-structure of the fat grafts was observed and evaluated using scanning electron microscope (SEM) and collagen I immunohistostaining. The gene transcription level of collagen proteins and the matrix metalloproteinases (MMPs) were assessed by qRT-PCR. Local injection of clodronate-encapsulated liposome was used to evaluate the role of macrophages of fat grafts at different stages in ECM remodeling, depletion of macrophages, at different time points (Week 1 and Week 4). Results: Results from the SEM analysis showed that liposuction caused severe damage to the ECM structure in freshly aspirated adipose tissue. On Day 1 post-transplantation, the surface of adipocytes was covered with platelets and this secreted fibrin network on the fat grafts. An integral adipose structure was already established with an intact ECM at the end of Week 1. The early depletion of macrophages remarkably hindered ECM reconstruction process by down-regulating the expression of collagen proteins and MMPs. Expression of Collagen I was significantly decreased after depletion of macrophages in both gene and protein levels. Results also showed that the depletion of macrophages at the later stage of fat grafting resulted in less fibrosis and capsule formation. Conclusion: Free fat aspirates undergo a prompt ECM reconstruction process and completed in the first week; this process can be initiated with platelets and mainly modulated by inflammatory cells such as macrophages. It was also observed that prolonged macrophage infiltration contributes to fibrosis and capsule formation in fat grafts. - Highlights: • Free fat aspirates undergo a prompt ECM reconstruction process in the first week. • The ECM reconstruction process is initiated with platelets and modulated by macrophages. • Depletion of macrophage in transferred fat resulted in delayed ECM reconstruction.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Fluorescence-labeled liposome accumulation in injured colon of a mouse model of T-cell transfer-mediated inflammatory bowel disease

Drug delivery systems maximize the efficacy of drugs by improving their pharmacokinetic profiles, pharmacodynamic effects, or both and reducing their adverse effects. One of the most advanced, clinically available formulations are liposome-encapsulated drugs. In this study, we aimed to determine if liposomes can selectively deliver compounds in gastrointestinal diseases. Initially, we evaluated the correlation between the diarrhea score and accumulation of fluorescence (FL)-labeled liposome using in vivo imaging systems in various disease states of an inflammatory bowel disease mouse model. The result showed that FL-labeled liposome accumulation and colon tissue weight, which reflect the disease state were highly and positively correlated. Then, to confirm the accumulation of liposomes at injured sites of the colon, we administered both FL-labeled liposomes and luminescence probes for detecting reactive oxygen species (ROS) to the mouse model. The imaging data showed that liposome accumulation tended to coincide with ROS detected sites and the correlation coefficient indicated a significantly positive correlation between liposome accumulation and ROS detection levels. Finally, we evaluated the involvement of macrophages in the uptake mechanism of the liposomes by analyzing the relationship between FL-labeled liposome accumulation and macrophage marker gene expression levels. The result showed that the expression of each macrophage marker gene and liposome accumulation showed a significant positive correlation. Therefore, the macrophages considerably contributed to the uptake mechanism of the liposomes. These data suggest that liposomes could be an attractive delivery tool for enhancing the accumulation of drug candidates through macrophages in injured colonic tissues. This approach is expected to provide new treatment options for patients with colitis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Preparation of cupric sulfate-based self-emulsifiable nanocomposites and their application to the photothermal therapy of colon adenocarcinoma

Highlights: • CuSO{sub 4} nanocomposites (NCs) were fabricated by hot-melt extrusion method. • Dispersion of CuSO{sub 4} in NCs was identified by several solid-state studies. • CuSO{sub 4} NCs exhibited improved photothermal therapeutic efficacies in Caco-2 cells. Nanocomposites (NCs) of cupric sulfate monohydrate (CuSO{sub 4}) were fabricated by hot-melt extrusion (HME) system equipped with twin screws. Micron-sized bulk powder of CuSO{sub 4} was dispersed in the mixture of surfactants (Span 80 and Tween 80) and hydrophilic polymer (polyethylene glycol (PEG) 6000) by HME process. Reduction of surface tension by surfactants and homogeneous dispersion in hydrophilic polymer along with HME technique were introduced to prepare CuSO{sub 4} NCs. Dispersion of CuSO{sub 4} NCs exhibited approximately 204 nm hydrodynamic size, unimodal size distribution, and positive zeta potential values. Encapsulation of CuSO{sub 4} in CuSO{sub 4} NCs and the physicochemical interactions between CuSO{sub 4} and pharmaceutical excipients were investigated by solid-state studies. Of note, CuSO{sub 4} NCs group exhibited higher antiproliferation efficacies, compared with bulk CuSO{sub 4}, in Caco-2 (human adenocarcinoma) cells at 75 and 100 μg/mL CuSO{sub 4} concentrations (p < 0.05). Also, near-infrared laser irradiation to CuSO{sub 4} NCs group elevated the antiproliferation efficacies, compared with non-irradiation group, in Caco-2 cells. After intravenous injection in mice, CuSO{sub 4} NCs did not show severe in vivo toxicities. Developed CuSO{sub 4} NCs can be one of promising candidates of photothermal therapeutic agents for colon cancers.

60 APPLIED LIFE SCIENCES↗