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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 487 records · Page 27
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Energy storage-based packetized delivery of electricity

Systems and methods for Energy Storage-based Packetized Delivery of Electricity (ES-PDE) are disclosed that are radically different from the operation of today's grid. Using ES-PDE, the loads are powered by the energy storage systems (ESS) the majority of the time and only receive packets of electricity periodically to charge the ESSs. Therefore, the grid operators can schedule the delivery of electricity packets to utilize the existing grid infrastructure. Since the customers are powered by the co-located ESSs they are not impacted by the grid operation in short term. Therefore, when grid outages occur, the customers still have power for some time, giving the grid more time to be fully restored.

Nguyen, Tu Anh↗
DOE OSTI2024

Immolative cell-penetrating complexes for nucleic acid delivery to the lung

There are provided herein, inter alia, cationic amphipathic polymers, complexes, and compositions comprising same, and methods for their use including for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acids, into a cell. The complexes, compositions and methods may facilitate delivery and targeted release of the therapeutic, diagnostic and imaging agents to particular cell types and tissues.

Blake, Tim R.↗
DOE OSTI2019

Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery

Nanomedicine is a promising, noninvasive approach to reduce atherosclerotic plaque burden. However, drug delivery is limited without the ability of nanocarriers to sense and respond to the diseased microenvironment. Here, nanomaterials are developed from peptide amphiphiles (PAs) that respond to the increased levels of matrix metalloproteinases 2 and 9 (MMP2/9) or reactive oxygen species (ROS) found within the atherosclerotic niche. A pro-resolving therapeutic, Ac2-26, derived from annexin-A1 protein, is tethered to PAs using peptide linkages that cleave in response to MMP2/9 or ROS. By adjusting the molar ratios and processing conditions, the Ac2-26 PA can be co-assembled with a PA containing an apolipoprotein A1-mimetic peptide to create a targeted, therapeutic nanofiber (ApoA1-Ac226 PA). The ApoA1-Ac2-26 PAs demonstrate release of Ac2-26 within 24 h after treatment with MMP2 or ROS. The niche-responsive ApoA1-Ac2-26 PAs are cytocompatible and reduce macrophage activation from interferon gamma and lipopolysaccharide treatment, evidenced by decreased nitric oxide production. Interestingly, the linkage chemistry of ApoA1-Ac2-26 PAs significantly affects macrophage uptake and retention. Taken together, these findings demonstrate the potential of PAs to serve as an atheroma niche-responsive nanocarrier system to modulate the inflammatory microenvironment, with implications for atherosclerosis treatment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Overcoming Barriers Associated with Oral Delivery of Differently Sized Fluorescent Core‐Shell Silica Nanoparticles

Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, in this study, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C’ dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C’ dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C’ dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Breast tumor-targeted drug delivery via polymer nanocarriers: Endogenous and exogenous strategies

Breast cancer, one of the most common types of cancer worldwide, has a high degree of malignancy while lacking efficient treatments. The off-target events frequently occurring in drug administration have been a major obstacle, which causes severe side effects to patients and reduces the therapeutic efficacy. An ideal medication should precisely target the specific site with precise control over concentration and duration. In recent years, there has been immense progress in polymer nanocarriers that demonstrate great potential in the targeted delivery. These nanocarriers are constructed from materials sensitive to a wide range of endogenous (e.g., pH, enzyme, redox) and exogenous stimuli (e.g., light, ultrasound, magnetic waves), driving cargo release to the targeted tissue or cells. Here, we elucidate the mechanism of current targeting strategies and the engineering methods to construct these targeting systems or to improve their targeting efficiency. Here we capture the recent progress in the targeted nanocarriers derived from polymers which span hydrogels and micelles, demonstrating their design and applications in chemo, hyperthermia, immuno, and gene therapies.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Synthesis and Characterization of a Novel pH-Sensitive Aluminum Crosslinked Carboxymethyl Tragacanth Beads for Extended and Enteric Drug Delivery

Carboxymethyl tragacanth (CM-TG) with a DS of 1.2 was synthesized and characterized for drug delivery using diclofenac sodium as a model drug. The mixture of CM-TG and drug was ionically crosslinked using aluminum chloride to form drug-loaded beads. The concentrations of 10 and 20% w/w solution of CM-TG were found to produce beads with acceptable qualities. The beads exhibited pH-dependent swelling. The highest swelling was observed at pH 6.8 which evidences the possibility to release the drug in the colon. FT-IR and TGA confirmed carboxymethylation of tragacanth and the absence of drug-polymer interaction. The diclofenac sodium entrapment efficiency was 30–35% while the loading varies from 4.5 to 18% w/w based upon the drug-polymer ratio. The beads could extend the drug release up to 180 min at pH 6.8. The pH-responsive CM-TG hydrogel beads are biocompatible and could be exploited as a new excipient in developing enteric release formulations.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Biomass Derived Antimicrobial Hybrid Cellulose Hydrogel with Green ZnO Nanoparticles for Curcumin Delivery and its Kinetic Modelling

Regenerated cellulose obtained from sugarcane bagasse was used for hydrogel preparation using epichlorohydrin (crosslinker) and green zinc oxide nanoparticles (ZNPs) which were phytosynthesised from musk melon seed extract. The synthesised ZNPs were characterised using FESEM and EDAX. The swelling capacity of the hydrogel was determined by swelling measurements. For drug delivery studies from hydrogel, curcumin was selected as the model drug for its appealing anticancer and antimicrobial activity. The presence of ZNPs and curcumin in the hybrid hydrogel was analysed using FTIR, XRD, TGA and SEM analysis. The drug loading efficiency was optimised by Taguchi method. The drug release studies were performed under varying pH and initial drug loading concentration. The kinetic studies showed the best fit with case II type of transport with polymer swelling as the drug release mechanism. Antimicrobial activity for curcumin loaded hybrid hydrogel and pure cellulose hydrogel was performed using Staphylococcus aureus (bacteria) and Trichophyton rubrum (fungi). Thus, the developed curcumin loaded biomass derived hybrid hydrogel could find potential application towards skin infective applications.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Gelatin/Gelatinized Sago Starch Biomembranes as a Drug Delivery System Using Rubber Latex as Plasticizer

Preparation and properties of gelatin and gelatin/gelatinized sago starch biomembranes as a drug delivery system are presented. Deproteinized natural rubber latex (DNRL) was chosen to blend as a plasticizer in biomembranes due to its elasticity. The opaque biomembranes were formed, and the effect of DNRL amounts (10–50 part per hundred of gelatin; phg) on mechanical properties of biomembranes was investigated. It was discovered that increasing the amounts of DNRL could decrease the brittleness of biomembranes. However, these DNRL blended biomembranes still swelled, dissolved in water, and eroded within 2 h. The 50 phg DNRL was further chosen for biomembrane preparations. Then, the 5–30 phg gelatinized sago starch which was prepared in-house was added. These gelatin/gelatinized sago starch biomembranes were homogenous and opaque. They portrayed good water uptake properties, and the highest values occurred in 20–30 min, then these biomembranes eroded slowly. Increasing the amounts of sago starch in biomembranes raised the water uptake rates but reduced the erosion properties. Biomembranes with and without starch blends showed the same tensile strengths. Their elongations at break increased when the amounts of starch were raised but still were lower than that of gelatin/DNRL biomembranes. The morphology, scanning electron microscopy, atomic force electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimeter, and X-ray diffractometer confirmed the compatibility of ingredients in biomembranes. Lidocaine and its hydrochloride salt were successfully incorporated in these biomembranes with good properties. The drug release and permeation of biomembrane showed good drug controlled release and were able to permeate through the pig skin.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Delivery of Conjugated Silicon Dioxide Nanoparticles Show Strong Anti-Proliferative Activities

Conjugation of different molecules is a promising approach to enhance the drug delivery and treatment. In the present study, here, we have synthesized silica oxide (SiO{sub 2}) nanoparticles conjugated with (3-Glycidyloxypropyl) trimethoxysilane (3GPS) and further reacted with 1,2,4-triazole (Tri), 3-aminotriazole (ATri), 5-aminetetrazole (Atet), imidazole (Imi). The structure, size, and morphology of nanocomposite materials were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) methods. These nanocomposite materials were tested on human colorectal carcinoma cells (HCT-116) to examine their anti-cancer capabilities by using MTT assay and morphometric analysis. Our results revealed that nanocomposite materials decreased cancer cell viability and cell proliferation and caused cell death in a concentration-dependent manner. Our findings demonstrate that SiO{sub 2}-conjugated nanocomposite materials possess strong anti-cancer capabilities and hold a great potential for the colon cancer treatments.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Effective delivery of recombinant proteins to rod photoreceptors via lipid nanovesicles

The potential of liposomes to deliver functional proteins in retinal photoreceptors and modulate their physiological response was investigated by two experimental approaches. First, we treated isolated mouse retinas with liposomes encapsulating either recoverin, an important endogenous protein operating in visual phototransduction, or antibodies against recoverin. We then intravitrally injected in vivo liposomes encapsulating either rhodamin B or recoverin and we investigated the distribution in retina sections by confocal microscopy. The content of liposomes was found to be released in higher amount in the photoreceptor layer than in the other regions of the retina and the functional effects of the release were in line with the current model of phototransduction. Our study sets the basis for quantitative investigations aimed at assessing the potential of intraocular protein delivery via biocompatible nanovesicles, with promising implications for the treatment of retinal diseases affecting the photoreceptor layer. - Highlights: • Recombinant proteins encapsulated in nano-sized liposomes injected intravitreally reach retinal photoreceptors. • The phototransduction cascade in rods is modulated by the liposome content. • Mathematical modeling predicts the alteration of the photoresponses following liposome fusion.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Drug delivery using polyhistidine peptide-modified liposomes that target endogenous lysosome

Cell-penetrating peptides (CPPs) can deliver payloads into cells by forming complexes with bioactive molecules via covalent or non-covalent bonds. Various CPPs have been applied in CPP-modified liposomes, and their effectiveness is highly regarded in liposomal drug delivery systems (DDSs). Previously, we have reported on the polyhistidine peptide (H16 peptide: HHHHHHHHHHHHHHHH-NH{sub 2}) as a new CPP. The H16 peptide has a higher cell-penetrating capacity than well-known CPPs and delivers small molecules such as fluorescent dyes, bioactive peptides, and proteins into mammalian cells. However, it is not known whether the H16 peptide can deliver large cargos such as liposomes into cells. To assess the potential of the H16 peptide, in this study, we developed H16 peptide-modified liposomes (H16-Lipo) and evaluated their effectiveness in a liposomal DDS. The H16-Lipo was prepared by inserting a stearyl-H16 peptide into the hydrophobic region of a liposome. The H16-Lipo was internalized into human fibrosarcoma cells via multiple endocytosis pathways and localized to intracellular lysosomes. Based on this result, we used the H16-Lipo as a lysosome-targeting DDS. The H16-Lipo delivered alpha-galactosidase A (GLA), one of the lysosomal enzymes, to intracellular lysosomes and improved the proliferation of GLA-knockdown cells. These results suggest that the H16-Lipo is an effective drug carrier for lysosomal enzymes in a lysosome-targeting DDS. The loss of lysosomal enzymes has been known to induce metabolic disorders, called lysosomal storage diseases (LSDs). Our findings indicate that this combination of the H16 peptide and a liposome is a promising candidate as a DDS for the treatment of LSDs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Multicenter Evaluation of Biochemical Relapse–Free Survival Outcomes for Intraoperatively Planned Prostate Brachytherapy Using an Automated Delivery System

Purpose: To report biochemical recurrence in prostate cancer treated with intraoperatively planned low-dose-rate prostate brachytherapy using an automated delivery system (IO-LDRB). Methods and Materials: Between 2003 and 2013, 2608 patients from 3 centers were treated with IO-LDRB as single-modality treatment for low or low-tier intermediate-risk prostate cancer. Databases from the 3 centers have been analyzed. These independent databases were collected prospectively. Patient, tumor, and treatment characteristics were then compared, Kaplan-Meier survival estimates of biochemical relapse–free survival (bRFS) were generated, and the Cox proportional hazards model was used to determine factors predicting for relapse. Results: A total of 2608 patients with a median follow-up of 4.7 (interquartile range, 3.1-6.9) years were analyzed. Median age was 64 (range, 42-84) years. In these patients, median initial prostate-specific antigen was 5.5 ng/mL, 74% were T1, and 26% were T2; 73% were Gleason 6, and 25% Gleason 7. Median percentage of biopsy cores positive was 33%, and median gland volume was 34.2 cm{sup 3}. Eleven percent of patients received hormones for a median of 3.0 months before implantation. Median seed activity was 0.437 mCi, D90 (dose covering 90% of the prostate volume) was 186.7 Gy, and V100 was 99.37%. Biochemical relapse was observed in 124 patients (4.8%), and median time to failure was 4.0 years. Predicted bRFS was 93% at 7 years. On Cox regression bRFS was dependent only on D90 at the time of implantation and prostate-specific antigen density. Conclusions: This study demonstrates that IO-LDRB is an effective treatment option for patients with low and low-tier intermediate-risk prostate cancer. Rates of biochemical relapse remain low several years after treatment. These results compared favorably to published manual preplan technique results.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Ultrasound-Mediated Gemcitabine Delivery Reduces the Normal-Tissue Toxicity of Chemoradiation Therapy in a Muscle-Invasive Bladder Cancer Model

Chemoradiation therapy is the standard of care in muscle-invasive bladder cancer (MIBC). Although agents such as gemcitabine can enhance tumor radiosensitivity, their side effects can limit patient eligibility and treatment efficacy. This study investigates ultrasound and microbubbles for targeting gemcitabine delivery to reduce normal-tissue toxicity in a murine orthotopic MIBC model.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Localized Delivery of Cisplatin to Cervical Cancer Improves Its Therapeutic Efficacy and Minimizes Its Side Effect Profile

Cervical cancer represents the fourth most frequent malignancy in the world among women, and mortality has remained stable for the past 4 decades. Intravenous cisplatin with concurrent radiation therapy is the standard-of-care for patients with local and regional cervical cancer. However, cisplatin induces serious dose-limiting systemic toxicities and recurrence frequently occurs. In this study, we aimed to develop an intracervical drug delivery system that allows cisplatin release directly into the tumor and minimize systemic side effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Nucleolin is expressed in patient-derived samples and glioblastoma cells, enabling improved intracellular drug delivery and cytotoxicity

Highlights: • Nucleolin is overexpressed in GSC sub-populations and non-stem glioblastoma cells; • Nucleolin enables intracellular targeted drug delivery in glioblastoma cells; • Nucleolin is overexpressed in glioblastoma patient-derived samples. One of the major challenges in Glioblastoma (GBM) therapy relates with the existence of glioma stem-like cells (GSCs), known to be chemo- and radio-resistant. GSCs and non-stem GBM cells have the ability to interchange, emphasizing the importance of identifying common molecular targets among those cell sub-populations. Nucleolin overexpression has been recently associated with breast cancer sub-populations with different stem-like phenotype. The goal of this work was to evaluate the potential of cell surface nucleolin as a target in GBM cells. Different levels of nucleolin expression resulted in a 3.4-fold higher association of liposomes targeting nucleolin (functionalized with the nucleolin-binding F3 peptide) in U87, relative to GBM11 glioblastoma cells. Moreover, nucleolin was suggested as a potential marker in OCT4-, NANOG-positive GSC, and in the corresponding non-stem GBM cells, as well as in SOX2-positive GSC. Doxorubicin delivered by liposomes targeting nucleolin enabled a level of cytotoxicity that was 2.5- or 4.6-fold higher compared to the non-targeted counterparts. Importantly, an overexpression of nucleolin was also observed in cells of patient-derived samples, as compared with normal brain. Overall, these results suggested nucleolin as a therapeutic target in GBM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Poly(lactic- co -glycolic acid) Nanoparticles as Delivery Systems for the Improved Administration of Radiotherapeutic Anticancer Agents

This letter reports the development of poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) as delivery systems that could potentially encapsulate and improve the administration of radiotherapeutic anticancer agents. Different metal ions (Ba, Gd, and Ce) were used as surrogates of α-emitting radionuclides ( 223 Ra, 225 Ac, and 227 Th), and their encapsulation within the PLGA NPs ( D h < 300 nm) was evaluated. The initial concentration of metal ions, the metal salt (nitrate vs chloride), and the presence of chelators influenced the concentration of surrogate ions within the PLGA NPs. This letter shows the potential of PLGA NPs to encapsulate radionuclides, particularly α-emitters, for their application in nuclear medicine.

62 RADIOLOGY AND NUCLEAR MEDICINE↗