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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 19 records

Microfabrication of a High-Throughput Nanochannel Delivery/Filtration System

A microfabrication process is proposed to produce a nanopore membrane for continuous passive drug release to maintain constant drug concentrations in the patient s blood throughout the delivery period. Based on silicon microfabrication technology, the dimensions of the nanochannel area, as well as microchannel area, can be precisely controlled, thus providing a steady, constant drug release rate within an extended time period. The multilayered nanochannel structures extend the limit of release rate range of a single-layer nanochannel system, and allow a wide range of pre-defined porosity to achieve any arbitrary drug release rate using any preferred nanochannel size. This membrane system could also be applied to molecular filtration or isolation. In this case, the nanochannel length can be reduced to the nanofabrication limit, i.e., 10s of nm. The nanochannel delivery system membrane is composed of a sandwich of a thin top layer, the horizontal nanochannels, and a thicker bottom wafer. The thin top layer houses an array of microchannels that offers the inlet port for diffusing molecules. It also works as a lid for the nanochannels by providing the channels a top surface. The nanochannels are fabricated by a sacrificial layer technique that obtains smooth surfaces and precisely controlled dimensions. The structure of this nanopore membrane is optimized to yield high mechanical strength and high throughput.

Ferrari, Mauro↗

Robotic Scaffolds for Tissue Engineering and Organ Growth

The aim of tissue engineering (TE) is to restore tissue and organ functions with minimal host rejection. TE is seen as a future solution to solve the crisis of donor organs for transplant, which faces a shortage expected only to increase in the future. In this innovation, a flexible and configurable scaffold has been conceived that mechanically stresses cells that are seeded on it, stimulating them to increased growth. The influence of mechanical stress/ loading on cell growth has been observed on all forms of cells. For example, for cartilages, studies in animals, tissue explants, and engineered tissue scaffolds have all shown that cartilage cells (chondrocytes) modify their extracellular matrix in response to loading. The chondrocyte EMC production response to dynamics of the physical environment (in vivo cartilage development) illustrates a clear benefit (better growth) when stressed. It has been shown that static and dynamic compression regulates PRG4 biosynthesis by cartilage explants. Mechanical tissue stimulation is beneficial and (flexible) scaffolds with movable components, which are able to induce mechanical stimulation, offer advantages over the fixed, rigid scaffold design. In addition to improved cell growth from physical/mechanical stimulation, additional benefits include the ability to increase in size while preserving shape, or changing shape. By making scaffolds flexible, allowing relative movement between their components, adding sensing (e.g., for detecting response of cells to drug release and to mechanical actions), building controls for drug release and movement, and building even simple algorithms for mapping sensing to action, these structures can actually be made into biocompatible and biodegradable robots. Treating them as robots is a perspective shift that may offer advantages in the design and exploitation of these structures of the future.

Stoica, Adrian↗

Gravisensing, apoptosis, and drug recovery in Taxus cell suspensions

Haploid and diploid cell suspensions of Taxus spp. were examined for their adaptive plasticity in response to simulated microgravity, unit gravity, and hypergravity. Cell suspensions produced the taxane, paclitaxel, (TAXOL (R)), which is useful for the treatment of various cancers. Amyloplasts contributed to taxane ring biosynthesis and to drug release at the cell wall. Drug-producing cells reacted as gravisensing osmotic tensiometers. In stressed cells, amyloplasts docked and fused in clusters to sites on the plasmalemma before taxane discharge into the culture medium. In simulated microgravity and compared to all other treatments, taxane production was reduced nearly 100-fold. The percent paclitaxel of total taxanes remained 3-to 6-fold greater, and biomass doubled. When p53-independent programmed cell death was induced, taxanes were released into the culture medium as free molecules (soluble and insoluble) or bound to membranes, nuclear fragments, xylan residues, and other particulate materials. Unit gravity and especially hypergravity promoted xylogenesis and significant drug overproduction. A model relating families of >touch = (TCH), taxane early response (TER), nuclear cycling, and apoptosis-regulating genes to gravisensing, cell wall modifications, and to taxane recovery accounted for most but not all of the observations.

Paclitaxel/biosynthesis↗

Neural Mechanism by which Gravitational Stimuli and Stress Affect the Secretion of Renin and Other Hormones

The serotonin-releasing drug p-chloroamphetamine (PCA), as well as L-propranolol and chloriasondamine were used in a study which established that the pathway from the hypothalamus to the kidneys is sympathetic. Which hypothalamic nuclei mediate the response to PCA is being investigated experiments are being conducted to determine a readily reproducible psychological stimulus to renin secretion that can be used in rats. The effects of equithesin, urethane, and inactin on plasma renin activity were examined in preparation for tilting experiments. The relation of vasopressin-secreting neurons in the brain sem to PCA response was explored in Brattleboro rats that are congenitally unable to produce vasopressin in their hypothalami.

Ganong, W. F.↗

Microcapsules and Methods for Making

Methods of forming multi-lamellar microcapsules having alternating layers of hydrophilic and hydrophobic immiscible liquid phases have been developed using different polymer/solvent systems. The methods use liquid-liquid diffusion and simultaneous lateral phase separation, controlled by proper timed-sequence exposures of immiscible phases and low shear mixing, to form narrow size distributions of spherical, multilamellar microcapsules. The use of special formulations of solubilized drugs, surfactants, and polymeric co-surfactants in aqueous vehicles which are dispersed in hydrocarbon solvents containing small quantities of oil, low molecular weight co-surfactants and glycerides that are aqueous insoluble enables the formation of unique microcapsules which can carry large amounts of pharmaceuticals in both aqueous and non-aqueous solvent compartments. The liquid microcapsules are quickly formed in a single step and can include a polymeric outer 'skin' which protects the microcapsules during physical manipulation or exposure to high shear forces. Water-in-oil and oil-in-water microcapsules have been formed both in 1 x g and in microgravity, which contain several types of drugs co-encapsulated within different fluid compartments inside the same microcapsule. Large, spherical multi-lamellar microcapsules have been formed including a cytotoxic drug co-encapsulated with a radiocontrast medium which has advantages for chemoembolization of vascular tumors. In certain cases, crystals of the drug form inside the microcapsules providing zero-order and first order, sustained drug release kinetics.

Morrison, Dennis R.↗

NASA Tech Briefs, April 2002

The contents include: 1) Application Briefs; 2) Sneak Preview of Sensors Expo; 3) The Complexity of the Diagnosis Problem; 4) Design Concepts for the ISS TransHab Module; 5) Characteristics of Supercritical Transitional Mixing Layers; 6) Electrometer for Triboelectric Evaluation of Materials; 7) Infrared CO2 Sensor With Built-In Calibration Chambers; 8) Solid-State Potentiometric CO Sensor; 9) Planetary Rover Absolute Heading Detection Using a Sun Sensor; 10) Concept for Utilizing Full Areas of STJ Photodetector Arrays; 11) Development of Cognitive Sensors; 12) Enabling Higher-Voltage Operation of SOl CMOS Transistors; 13) Estimating Antenna-Pointing Errors From Beam Squints; 14) Advanced-Fatigue-Crack-Growth and Fracture- Mechanics Program; 15) Software for Sequencing Spacecraft Actions; 16) Program Distributes and Tracks Organizational Memoranda; 16) Flat Membrane Device for Dehumidification of Air; 17) Inverted Hindle Mount Reduces Sag of a Large, Precise Mirror; 18) Heart-Pump-Outlet/Cannula Coupling; 19) Externally Triggered Microcapsules Release Drugs In Situ; 20) Combinatorial Drug Design Augmented by Information Theory; 21) Multiple-Path-Length Optical Absorbance Cell; 22) Model of a Fluidized Bed Containing a Mixture of Particles; 23) Refractive Secondary Concentrators for Solar Thermal Systems; 24) Cold Flow Calorimeter; 25) Methodology for Tracking Hazards and Predicting Failures; 26) Estimating Heterodyne-Interferometer Polarization Leakage; 27) An Efficient Algorithm for Propagation of Temporal- Constraint Networks; 28) Software for Continuous Replanning During Execution; 29) Surface-Launched Explorers for Reconnaissance/Scouting; 30) Firmware for a Small Motion-Control Processor; 31) Gear Bearings and Gear-Bearing Transmissions; and 32) Linear Dynamometer With Variable Stroke and Frequency.

Source record↗

Externally triggered microcapsules

Disclosed are microcapsules comprising a polymer shell enclosing one or more immiscible liquid phases in which a drug or drug precursor are contained in a liquid phase. The microparticles also contain magnetic particles that can be heated by application of an external magnetic field and thus heated to a predetermined Curie temperature. Heating of the particles melts the polymer shell and releases the drug without causing heating of surrounding tissues.

Morrison, Dennis R.↗

Polyphosphazenes - New polymers with inorganic backbone atoms

Unique and useful properties of the class of nonhydrocarbon, nonhalocarbon, nonsilicone polymers known as polyphosphazenes are discussed at length. These polymers, with molecular weights to 4 million (degree of polymerization 15,000), can be fabricated as tubes, fibers, woven fabrics, flexible films, or plates, and many variants are stable to attack by water, bases, aqueous acids, jet fuels, oils, hydraulic fluids, gasoline, or other hydrocarbons. Rubbery polymers with these properties can be fashioned into flexible hose, fuel hose, gaskets, or O-rings. Since they do not provoke clotting reactions in blood, and reveal no carcinogenic effects to date, they are considered for internal prosthetic applications (replacement bone, temporary skin, heart valves), as biodegradable suturing material, as carriers for slow release of drugs, and as carriers for chemotherapeutic agents against cancers.

Allcock, H. R.↗

Advanced composite applications for sub-micron biologically derived microstructures

A major thrust of advanced material development is in the area of self-assembled ultra-fine particulate based composites (micro-composites). The application of biologically derived, self-assembled microstructures to form advanced composite materials is discussed. Hollow 0.5 micron diameter cylindrical shaped microcylinders self-assemble from diacetylenic lipids. These microstructures have a multiplicity of potential applications in the material sciences. Exploratory development is proceeding in application areas such as controlled release for drug delivery, wound repair, and biofouling as well as composites for electronic and magnetic applications, and high power microwave cathodes.

Schnur, J. M.↗

Application of the ionscan for the detection of methamphetamine and ephedrine in abondoned clandestine laboratories

Clandestine methamphetamine laboratories are prevalent in southern California. The most common encountered synthesis results in vapor release, and drug residue being left behind. The suspected manufacturing area can be vacuumed and/or methanol wiped and screened immediately at the lab site using the Ionscan. Positive results are confirmed by obtaining vacuum sweep samples with subsequent analysis at the DEA Laboratory. This procedure has been utilized successfully for identifying methamphetamine and ephedrine from clandestine laboratories that have been abandoned and/or remodeled.

Brown, Patricia A.↗

Utilization of peptide carrier system to improve intestinal absorption: targeting prolidase as a prodrug-converting enzyme

The feasibility of targeting prolidase as a peptide prodrug-converting enzyme has been examined. The enzymatic hydrolysis by prolidase of substrates for the peptide transporter L-alpha-methyldopa-pro and several dipeptide analogues without an N-terminal alpha-amino group (phenylpropionylproline, phenylacetylproline, N-benzoylproline, and N-acetylproline) was investigated. The Michaelis-Menten parameters Km and Vmax for L-alpha-methyldopa-pro are 0.09 +/- 0.02 mM and 3.98 +/- 0.25 mumol/min/mg protein, respectively. However, no hydrolysis of the dipeptide analogues without an N-terminal alpha-amino group is observed, suggesting that an N-terminal alpha-amino group is required for prolidase activity. These results demonstrate that prolidase may serve as a prodrug-converting enzyme for the dipeptide-type prodrugs, utilizing the peptide carrier for transport of prodrugs into the mucosal cells and prolidase, a cytosolic enzyme, to release the drug. However, a free alpha-amino group appears to be necessary for prolidase hydrolysis.

NASA Discipline Regulatory Physiology↗

Effects of methiothepin on changes in brain serotonin release induced by repeated administration of high doses of anorectic serotoninergic drugs

We previously observed, using in vivo microdialysis, that the potassium-evoked release of frontocortical serotonin (5-HT) is suppressed after rats receive high doses (30 mg/kg, i.p., daily for 3 days) of fluoxetine, a selective blocker of 5-HT reuptake. We now describe similar impairments in 5-HT release after repeated administration of two other 5-HT uptake blockers, zimelidine and sertraline (both at 20 mg/kg, i.p. for 3 days) as well as after dexfenfluramine (7.5 mg/kg, i.p. daily for 3 days), a drug which both releases 5-HT and blocks its reuptake. Doses of these indirect serotonin agonists were about 4-6 times the drug's ED50 in producing anorexia, a serotonin-related behavior. In addition, methiothepin (20 microM), a non-selective receptor antagonist, locally perfused through the dialysis probe 24 h after the last drug injection, enhanced K(+)-evoked release of 5-HT at serotoninergic nerve terminals markedly in control rats and slightly in rats treated with high doses of dexfenfluramine or fluoxetine. On the other hand, pretreatment with methiothepin (10 mg/kg, i.p.) one hour before each of the daily doses of fluoxetine or dexfenfluramine given for 3 days, totally prevented the decrease in basal and K(+)-evoked release of 5-HT. Finally, when methiothepin was injected systemically the day before the first of 3 daily injections of dexfenfluramine, it partially attenuated the long-term depletion of brain 5-HT and 5-HIAA levels induced by repeated administration of high doses of dexfenfluramine. These data suggest that drugs which bring about the prolonged blockade of 5-HT reuptake - such as dexfenfluramine and fluoxetine - can, by causing prolonged increases in intrasynaptic 5-HT levels as measured by in vivo microdialysis, produce receptor-mediated long-term changes in the processes controlling serotonin levels and dynamics.

NASA Discipline Regulatory Physiology↗

Fabrication and Modification of Nanoporous Silicon Particles

Silicon-based nanoporous particles as biodegradable drug carriers are advantageous in permeation, controlled release, and targeting. The use of biodegradable nanoporous silicon and silicon dioxide, with proper surface treatments, allows sustained drug release within the target site over a period of days, or even weeks, due to selective surface coating. A variety of surface treatment protocols are available for silicon-based particles to be stabilized, functionalized, or modified as required. Coated polyethylene glycol (PEG) chains showed the effective depression of both plasma protein adsorption and cell attachment to the modified surfaces, as well as the advantage of long circulating. Porous silicon particles are micromachined by lithography. Compared to the synthesis route of the nanomaterials, the advantages include: (1) the capability to make different shapes, not only spherical particles but also square, rectangular, or ellipse cross sections, etc.; (2) the capability for very precise dimension control; (3) the capacity for porosity and pore profile control; and (4) allowance of complex surface modification. The particle patterns as small as 60 nm can be fabricated using the state-of-the-art photolithography. The pores in silicon can be fabricated by exposing the silicon in an HF/ethanol solution and then subjecting the pores to an electrical current. The size and shape of the pores inside silicon can be adjusted by the doping of the silicon, electrical current application, the composition of the electrolyte solution, and etching time. The surface of the silicon particles can be modified by many means to provide targeted delivery and on-site permanence for extended release. Multiple active agents can be co-loaded into the particles. Because the surface modification of particles can be done on wafers before the mechanical release, asymmetrical surface modification is feasible. Starting from silicon wafers, a treatment, such as KOH dipping or reactive ion etching (RIE), may be applied to make the surface rough. This helps remove the nucleation layer. A protective layer is then deposited on the wafer. The protective layer, such as silicon nitride film or photoresist film, protects the wafer from electrochemical etching in an HF-based solution. A lithography technique is applied to pattern the particles onto the protective film. The undesired area of the protective film is removed, and the protective film on the back side of the wafer is also removed. Then the pattern is exposed to HF/surfactant solution, and a larger DC electrical current is applied to the wafers for a selected time. This step removes the nucleation layer. Then a DC current is applied to generate the nanopores. Next, a large electrical current is applied to generate a release layer. The particles are mechanically suspended in the solvent and collected by filtration or centrifuge.

Ferrari, Mauro↗

Nanochanneled Device and Related Methods

A nanochannel delivery device and method of manufacturing and use. The nanochannel delivery device comprises an inlet, an outlet, and a nanochannel. The nanochannel may be oriented parallel to the primary plane of the nanochannel delivery device. The inlet and outlet may be in direct fluid communication with the nanochannel. Considerable advances have been made in the field oftherapeutic agent (e.g. drug) delivery technology over thelast three decades, resulting in many breakthroughs in clinicalmedicine. The creation of therapeutic agent deliverydevices that are capable of delivering therapeutic agents incontrolled ways is still a challenge. One of the majorrequirements for an implantable drug delivery device iscontrolled release of therapeutic agents, ranging from smalldrug molecules to larger biological molecules. It is particularlydesirable to achieve a continuous passive drug releaseprofile consistent with zero order kinetics whereby theconcentration of drug in the bloodstream remains constantthroughout an extended delivery period.These devices have the potential to improve therapeuticefficacy, diminish potentially life-threatening side effects,improve patient compliance, minimize the intervention ofhealthcare personnel, reduce the duration of hospital stays,and decrease the diversion of regulated drugs to abusiveuses.Nanochannel delivery devices may be used in drug deliveryproducts for the effective administration of drugs. Inaddition, nanochannel delivery devices can be used in otherapplications where controlled release of a substance overtime is needed. Embodiments of this invention comprise a nanochanneldelivery device having nanochannels within a structureconfigured to yield high mechanical strength and high flowrates. Various fabrication protocols may be used to form thenanochannel delivery device. Embodiments of the fabricateddevices feature horizontal nanochannel lay-out (e.g., thenanochannel is parallel to the primary plane of the device),high molecule transport rate, high mechanical strength,optional multilayered lay-out, amenability to select channellining materials, and possible transparent top cover. Basedon silicon microfabrication technology, the dimensions ofthe nanochannel area as well as concomitant microchannelareas can be precisely controlled, thus providing a predictable,reliable, constant release rate of drug (or other) moleculesover an extended time period. In certain embodiments,the nanochannel delivery device can be used to builda multilayered nanochannel structure.

Ferrari, Mauro↗

Effect of chronic d-fenfluramine administration on rat hypothalamic serotonin levels and release

D-fenfluramine, an anorectic agent in rats and man, was administered daily at doses 1.25, 2.5, 5, or 10 mg/kg/day for 10 days, and sacrificed 6 days later. Hypothalamic serotonin (5-HT) levels were unchanged in rats receiving 1.25-5 mg/kg/day of d-fenfluramine but reduced by 22 percent (p less than 0.01) at the highest drug dose (10 mg/kg/day); hypothalamic 5-hydroxyindole acetic acid (5-HIAA) levels were reduced by 15 percent (p less than 0.05) or 28 percent (p less than 0.01) in rats receiving 5 or 10 mg/kg/day of the drug, respectively. Hypothalamic slices prepared from rats which were previously treated with any of the drug doses spontaneously released endogenous 5-HT at rates that did not differ from those of vehicle-treated rats. 5-HT released with electrical field-stimulation was unaffected by prior d-fenfluramine treatment at doses of 1.25-5 mg/kg/day, and was reduced by 20 percent (p less than 0.05) from slices prepared from rats which received 10 mg/kg/day. 5-HIAA efflux was also attenuated by the highest drug dose. These data indicate that chronic administration to rats of customary anorectic doses of d-fenfluramine (i.e. 0.06-1.25 mg/kg) fail to cause long-lasting reductions in brain 5-HT release.

Schaechter, Judith D.↗

Caffeine potentiates the enhancement by choline of striatal acetylcholine release

We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

Non-NASA Center↗

Peptides and neurotransmitters that affect renin secretion

Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the pathway by which psychosocial stimuli increase renin secretion.

Review↗

Microencapsulation of anti-tumor, antibiotic and thrombolytic drugs in microgravity

Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.

Morrison, Dennis R.↗