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Results for “DRUG DELIVERY”

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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal–Organic Framework (MOF)

Encapsulating a drug molecule into a water-reactive metal–organic framework (MOF) leads to amorphous drug confined within the nanoscale pores. Rapid release of drug occurs upon hydrolytic decomposition of MOF in dissolution media. Application to improve dissolution and solubility for the hydrophobic small drug molecules curcumin, sulindac, and triamterene is demonstrated. The drug@MOF composites exhibit significantly enhanced dissolution and achieves high supersaturation in simulated gastric and/or phosphate buffer saline media. This combination strategy where MOF inhibits crystallization of the amorphous phase and then releases drug upon MOF irreversible structural collapse represents a novel and generalizable approach for drug delivery of poorly soluble compounds while overcoming the traditional weakness of amorphous drug delivery: physical instability of the amorphous form.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal–Organic Framework (MOF)

Abstract Encapsulating a drug molecule into a water‐reactive metal–organic framework (MOF) leads to amorphous drug confined within the nanoscale pores. Rapid release of drug occurs upon hydrolytic decomposition of MOF in dissolution media. Application to improve dissolution and solubility for the hydrophobic small drug molecules curcumin, sulindac, and triamterene is demonstrated. The drug@MOF composites exhibit significantly enhanced dissolution and achieves high supersaturation in simulated gastric and/or phosphate buffer saline media. This combination strategy where MOF inhibits crystallization of the amorphous phase and then releases drug upon MOF irreversible structural collapse represents a novel and generalizable approach for drug delivery of poorly soluble compounds while overcoming the traditional weakness of amorphous drug delivery: physical instability of the amorphous form.

Suresh, Kuthuru↗
DOE OSTI2019

Modular Metal–Organic Polyhedra Superassembly: From Molecular‐Level Design to Targeted Drug Delivery

Abstract Targeted drug delivery remains at the forefront of biomedical research but remains a challenge to date. Herein, the first superassembly of nanosized metal–organic polyhedra (MOP) and their biomimetic coatings of lipid bilayers are described to synergistically combine the advantages of micelles and supramolecular coordination cages for targeted drug delivery. The superassembly technique affords unique hydrophobic features that endow individual MOP to act as nanobuilding blocks and enable their superassembly into larger and well‐defined nanocarriers with homogeneous sizes over a broad range of diameters. Various cargos are controllably loaded into the MOP with high payloads, and the nanocages are then superassembled to form multidrug delivery systems. Additionally, functional nanoparticles are introduced into the superassemblies via a one‐pot process for versatile bioapplications. The MOP superassemblies are surface‐engineered with epidermal growth factor receptors and can be targeted to cancer cells. In vivo studies indicated the assemblies to have a substantial circulation half‐life of 5.6 h and to undergo renal clearance—characteristics needed for nanomedicines.

Zhu, Wei↗
DOE OSTI2023

Electrospun PVA Fibers for Drug Delivery: A Review

Innovation in biomedical science is always a field of interest for researchers. Drug delivery, being one of the key areas of biomedical science, has gained considerable significance. The utilization of simple yet effective techniques such as electrospinning has undergone significant development in the field of drug delivery. Various polymers such as PEG (polyethylene glycol), PLGA (Poly(lactic-co-glycolic acid)), PLA(Polylactic acid), and PCA (poly(methacrylate citric acid)) have been utilized to prepare electrospinning-based drug delivery systems (DDSs). Polyvinyl alcohol (PVA) has recently gained attention because of its biocompatibility, biodegradability, non-toxicity, and ideal mechanical properties as these are the key factors in developing DDSs. Moreover, it has shown promising results in developing DDSs individually and when combined with natural and synthetic polymers such as chitosan and polycaprolactone (PCL). Considering the outstanding properties of PVA, the aim of this review paper was therefore to summarize these recent advances by highlighting the potential of electrospun PVA for drug delivery systems.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Evaluation of Three Morphologically Distinct Virus-Like Particles as Nanocarriers for Convection-Enhanced Drug Delivery to Glioblastoma

Glioblastoma is a particularly challenging cancer, as there are currently limited options for treatment. New delivery routes are being explored, including direct intratumoral injection via convection-enhanced delivery (CED). While promising, convection-enhanced delivery of traditional chemotherapeutics such as doxorubicin (DOX) has seen limited success. Several studies have demonstrated that attaching a drug to polymeric nanoscale materials can improve drug delivery efficacy via CED. We therefore set out to evaluate a panel of morphologically distinct protein nanoparticles for their potential as CED drug delivery vehicles for glioblastoma treatment. The panel consisted of three different virus-like particles (VLPs), MS2 spheres, tobacco mosaic virus (TMV) disks and nanophage filamentous rods modified with DOX. While all three VLPs displayed adequate drug delivery and cell uptake in vitro, increased survival rates were only observed for glioma-bearing mice that were treated via CED with TMV disks and MS2 spheres conjugated to doxorubicin, with TMV-treated mice showing the best response. Importantly, these improved survival rates were observed after only a single VLP–DOX CED injection several orders of magnitude smaller than traditional IV doses. Overall, this study underscores the potential of nanoscale chemotherapeutic CED using virus-like particles and illustrates the need for further studies into how the overall morphology of VLPs influences their drug delivery properties.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Endothelial surface translocation of mitochondrial PDCE2 involves the non-canonical secretory autophagy pathway: Putative molecular target for radiation-guided drug delivery

Highlights: • Radiation induces ectopic endothelial surface exposure of mitochondrial PDCE2. • PDCE2 translocation is associated with late-stage inhibition of autophagic flux. • Radiation damage overloads the degradative lysosomal pathway of autophagy. • PDCE2 trafficking occurs via autophagosomes and non-canonical secretory autophagy. • Surface PDCE2 provides a novel target for radiation-guided vascular drug delivery. Radiation has been proposed as a priming agent to induce discriminatory luminal biomarkers for vascular targeting and drug delivery in disorders such as brain arteriovenous malformations and cancers. We previously observed ectopic expression of intracellular proteins such as mitochondrial PDCE2 on irradiated endothelium in animal models. In this study we examined the mechanism of PDCE2 trafficking in human endothelial cells to better understand its suitability as a vascular target. Ionizing radiation induced PDCE2 surface localization in association with accumulation of autophagosome markers (L3CB and p62) indicative of late-stage inhibition of autophagic flux. This effect was abolished in the presence of Rapamycin, an autophagy-inducer, but replicated in the presence of Bafilomycin A, an autophagy blocker. PDCE2 co-localized with lysosomal markers of the canonical degradative autophagy pathway in response to radiation but also with recycling endosomes and SNARE proteins responsible for autophagosome-plasma membrane fusion. These findings demonstrate that radiation-induced blockade of autophagic flux stimulates redirection of intracellular molecules such as PDCE2 to the cell surface via a non-canonical secretory autophagy pathway. Intracellular membrane proteins trafficked in this way could provide a unique pool of radiation biomarkers for therapeutic drug delivery.

60 APPLIED LIFE SCIENCES↗
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 OSTI2025

Dynamic Nanopeptide Assemblies for Trans-Tympanic Drug Delivery

Aim: Otitis media is a common otolaryngologic diagnosis worldwide. Invasive methods to curtail and treat frequent occurrences are undesirable, thus necessitating the identification and production of a non-invasive approach to treating the disease. Due to tympanic membrane thickness, ototopical drug delivery is challenging. In this preliminary study, formulations integrating nanopeptides and thermoresponsive polymeric hydrogels are utilized to improve the efficiency of trans-tympanic membrane drug delivery. Methods: Peptides were synthesized using standard Fmoc (fluorenylmethoxycarbonyl protecting group) based solid state peptide synthesis on an automated peptide synthesizer. Ciprofloxacin release was simulated using multiwell microplates with porous inserts. Rate of Ciprofloxacin release was measured over a 48-hour period using a 200 uL solution of peptide fibers and Ciprofloxacin at 1 wt% each, and the labeled peptide at 0.1 wt% in PBS at pH of 7.4. The cytotoxicity of the PA (peptide amphiphile, specifically c16-AHL 3 K 3 -CO 2 H) micelle and fiber with and without ciprofloxacin was investigated by examining epidermal keratinocyte viability in the presence of the material at various concentrations. Laser scanning confocal microscopy was performed with excitation of the calcein dye at 485 nm and the PA-TAMRA (rhodamine labeled peptide) at 515 nm. Results: We have demonstrated the potential viability of a self-assembled peptide amphiphile hydrogel capable of transitioning from a network of 1D nanoscale fibers to 0D micelles. This dissociative mechanism of action yields a peptide that is an effective cell penetrating peptide (CPP) while temporally controlling the release of the antibiotic ciprofloxacin. Conclusion: This work highlights the potential utility of the dynamic process of an engineered peptide hydrogel capable of dissociating into CPPs capable of facilitating drug delivery across the tympanic membrane.

cell culture↗
DOE OSTI2018

Porous Silicon as a Nanomaterial for Disperse Transport Systems of Targeted Drug Delivery to the Inner Ear

The samples of porous silicon (por-Si) particles in three size ranges (60–80, 250–300, and 500–600 nm) are obtained by electrochemical anodic etching of single-crystal silicon in an electrolyte based on an HF solution, followed by a change in the modes of ultrasonic treatment and homogenization. A complex characterization of particles was carried out by scanning electron microscopy, photon cross-correlation spectroscopy, and X-ray photoelectron spectroscopy. In vitro biocompatibility models using unicellular organisms of infusoria Paramecium caudatum Keln are applied to demonstrate the low toxicity of the samples at concentrations used for intravenous administration. The systemic in vivo biodistribution was studied for the por-Si 60–80 nm sample using adult Wistar rats. Introduced nanoobjects are found in the liver and heart tissues without significant changes in shape or size and predominantly in the oxidized state. Possibilities of using por-Si samples as matrices for transporting pharmaceuticals with intravenous administration are studied by assessing the intensity of the ototropic effect of gentamicin. An objective audiologic method for studying the amplitude of otoacoustic emission revealed the largest otodepressive effect of gentamicin when submicrometer-sized por-Si particles (500–600 nm) was used as a disperse system for drug delivery. Thus, modifications of the conditions for the synthesis of por-Si nanoparticles are promising directions in obtaining physicochemical parameters of transport particles that are optimal for specific tasks of targeted drug delivery.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2018

Microneedle arrays for biosensing and drug delivery

Methods, structures, and systems are disclosed for biosensing and drug delivery techniques. In one aspect, a device for detecting an analyte and/or releasing a biochemical into a biological fluid can include an array of hollowed needles, in which each needle includes a protruded needle structure including an exterior wall forming a hollow interior and an opening at a terminal end of the protruded needle structure that exposes the hollow interior, and a probe inside the exterior wall to interact with one or more chemical or biological substances that come in contact with the probe via the opening to produce a probe sensing signal, and an array of wires that are coupled to probes of the array of hollowed needles, respectively, each wire being electrically conductive to transmit the probe sensing signal produced by a respective probe.

47 OTHER INSTRUMENTATION↗
DOE OSTI2024

Machine Learning of Performance Space Mapping for the DPD Simulation of Drug Delivery to Endothelial Cells

Despite huge effort over the years, the design of functionalised nanocarriers (NCs) for targeted drug delivery to endothelial cells is still to be completely unveiled. Dissipative particle dynamics (DPD) simulation is used to study the adhesion of NCs to endothelial cells under the influence of series of parameters such as shape, size, and ligand density of the NCs. However, preparing a performance space mapping that illustrates the penetration depths of NCs as a function of variations in their properties requires simulations of all possible NCs with the above-mentioned properties, which is not feasible. This challenge was addressed by leveraging a Gaussian process regression (GPR)-informed active learning strategy and an extensive exploration of numerous samples, each representing different properties of NCs. The performance space mapping reveals that NCs with rod and disc shapes exhibit superior penetration capabilities compared to those with a spherical shape. Furthermore, it demonstrates that smaller-sized rod-shaped NCs and larger-sized disc-shaped NCs tend to achieve better penetration. When considering smaller NCs, the influence of ligand density appears to be limited. On the contrary, for larger NCs, an increase in ligand density correlates with greater penetration depth, underscoring its substantial role in shaping their penetration capabilities.

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 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 OSTI2019

Amphiphilic Polypeptoids Rupture Vesicle Bilayers To Form Peptoid–Lipid Fragments Effective in Enhancing Hydrophobic Drug Delivery

Peptoids are highly biocompatible pseudopeptidic polyglycines with designable substituents on the nitrogen atoms. The therapeutic and drug-carrying potential of these materials requires a fundamental understanding of their interactions with lipid bilayers. Here, we use amphiphilic polypeptoids with up to 100 monomeric units where a significant fraction (26%) of the nitrogen atoms are functionalized with decyl groups (hydrophobes) that insert into the lipid bilayer through the hydrophobic effect. These hydrophobically modified polypeptoids (HMPs) insert their hydrophobes into lipid bilayers creating instabilities that lead to the rupture of vesicles. At low HMP concentrations, such rupture leads to the creation of large fragments which remarkably anchor to intact vesicles through the hydrophobic effect. At high HMP concentrations, all vesicles rupture to smaller HMP–lipid fragments of the order of 10 nm. We show that the technique for such nanoscale polymer–lipid fragments can be exploited to sustain highly hydrophobic drug species in solution. Using the kinase inhibitor, Sorafenib as a model drug, it is shown that HMP–lipid fragments containing the drug can efficiently enter a hepatocellular carcinoma cell line (Huh 7.5), indicating the use of such fragments as drug delivery nanocarriers.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗
DOE OSTI2020

Magnetic properties of γ-Fe 2 O 3 nanoparticles in a porous SiO 2 shell for drug delivery

A method is presented for synthesizing core–shell nanoparticles with a magnetic core and a porous shell suitable for drug delivery and other medical applications. The core contains multiple γ -Fe 2 O 3 nanoparticles (~15 nm) enclosed in a SiO 2 (~100–200 nm) matrix using either methyl (denoted TMOS- γ -Fe 2 O 3 ) or ethyl (TEOS- γ -Fe 2 O 3 ) template groups. Low-temperature Mössbauer spectroscopy showed that the magnetic nanoparticles have the maghemite structure, γ -Fe 2 O 3 , with all the vacancies in the octahedral sites. Saturation magnetization measurements revealed that the density of γ -Fe 2 O 3 was greater in the TMOS- γ -Fe 2 O 3 nanoparticles than TEOS- γ -Fe 2 O 3 nanoparticles, presumably because of the smaller methyl group. Magnetization measurements showed that the blocking temperature is around room temperature for the TMOS- γ -Fe 2 O 3 and around 250 K for the TEOS- γ -Fe 2 O 3 . Three dimensional topography analysis shows clearly that the magnetic nanoparticles are not only at the surface but have penetrated deep in the silica to form the core–shell structure.

Physics↗