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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

All sources NASA NTRS DOE OSTI

NASA NTRS2010

Microfluidic device for drug delivery

A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

Beebe, David J.↗

NASA NTRS2014

Micro-Fluidic Device for Drug Delivery

Beebe, David J.↗

NASA NTRS2012

Nano Sponges for Drug Delivery and Medicinal Applications

This invention is a means of delivering a drug, or payload, to cells using non-covalent associations of the payload with nano-engineered scaffolds; specifically, functionalized single-walled carbon nanotubes (SWNTs) and their derivatives where the payload is effectively sequestered by the nanotube's addends and then delivered to the site (often interior of a cell) of interest. Polyethylene glycol (PEG) and other water-soluble organic molecules have been shown to greatly enhance the solubility of SWNTs in water. PEG groups and other water-solubilizing addends can act to sequester (sponge) molecules and deliver them into cells. Using PEG that, when attached to the SWNTs, the SWNT/PEG matrix will enter cells has been demonstrated. This was visualized by the addition of fluorescein isothiocyanate (FITC) to the SWNT/PEG matrix. Control studies showed that both FITC alone and FITC/PEG did not enter the cells. These observations suggest that the FITC is highly associated with the SWNT/PEG matrix that brings the FITC into the cells, allowing visualization of SWNTs in cells. The FITC is not covalently attached, because extended dialysis in hot DMF will remove all fluorescence quickly (one week). However, prolonged dialysis in water (1-2 months) will only slowly diminish the fluorescence. This demonstrates that the SWNT/PEG matrix solubilizes the FITC by sequestering it from the surrounding water and into the more solubilizing organic environment of the SWNT/PEG matrix of this type. This can be extended for the sequestering of other molecules such as drugs with PEG and other surfactants.

Tour, James M.↗

NASA NTRS1992

Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery

The brush border membrane of intestinal mucosal cells contains a peptide carrier system with rather broad substrate specificity and various endo- and exopeptidase activities. Small peptide (di-/tripeptide)-type drugs with or without an N-terminal alpha-amino group, including beta-lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Polypeptide drugs are hydrolyzed by brush border membrane proteolytic enzymes to di-/tripeptides and amino acids. Therefore, while the intestinal brush border membrane has a carrier system facilitating the absorption of di-/tripeptide drugs, it is a major barrier limiting oral availability of polypeptide drugs. In this paper, the specificity of peptide transport and metabolism in the intestinal brush border membrane is reviewed.

Review, Tutorial↗

NASA NTRS2003

Alternating-pulse iontophoresis for targeted cutaneous anesthesia

In studies of sensory contributions to motor control, it may be advantageous to temporarily reduce the sensitivity of specific sensory systems. This article details a method for non-invasively inducing cutaneous anesthesia, leaving proprioceptive and motor functions intact. This method, called alternating-pulse iontophoresis, differs from conventional direct-current (DC) iontophoretic drug delivery in that adjacent drug delivery electrodes are stimulated out-of-phase. The total current delivered at any instant is then less than that produced during a comparable DC application, while the uniformity of drug delivery is expected to improve. Effective delivery of local anesthetics to the cutaneous foot soles by alternating-pulse iontophoresis was demonstrated using cutaneous pressure sensory threshold levels (STL's) assessed with Semmes-Weinstein monofilaments (arbitrary units of perceived force, or a.u.). Thirteen of 16 healthy subjects achieved a level of anesthesia greater than or equal to that normally associated with clinical peripheral sensory neuropathy. Average STL's measured prior to the anesthesia procedure were 4.00 a.u. ( approximately 10 mN). Immediately following the procedure, STL's were elevated to an average of 5.40 a.u. ( approximately 246 mN) and averaged 4.97 a.u. ( approximately 92 mN) after 50 min of standing. A number of research and clinical applications for this technique are suggested.

Non-NASA Center↗

NASA NTRS2003

Biomaterials and Magnetic fields for Cancer Therapy

The field of biomaterials has emerged as an important topic in the purview of NASA s new vision of research activities in the Microgravity Research Division. Although this area has an extensive track record in the medical field as borne out by the routine use of polymeric sutures, implant devices, and prosthetics, novel applications such as tissue engineering, artificial heart valves and controlled drug delivery are beginning to be developed. Besides the medical field, biomaterials and bio-inspired technologies are finding use in a host of emerging interdisciplinary fields such as self-healing and self-assembling structures, biosensors, fuel systems etc. The field of magnetic fluid technology has several potential applications in medicine. One of the emerging fields is the area of controlled drug delivery, which has seen its evolution from the basic oral delivery system to pulmonary to transdermal to direct inoculations. In cancer treatment by chemotherapy for example, targeted and controlled drug delivery has received vast scrutiny and substantial research and development effort, due to the high potency of the drugs involved and the resulting requirement to keep the exposure of the drugs to surrounding healthy tissue to a minimum. The use of magnetic particles in conjunction with a static magnetic field allows smart targeting and retention of the particles at a desired site within the body with the material transport provided by blood perfusion. Once so located, the therapeutical aspect (radiation, chemotherapy, hyperthermia, etc.) of the treatment, now highly localized, can be implemented.

Ramachandran, Narayanan↗

NASA NTRS2016

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↗

NASA NTRS2011

Method for Impeding Degradation of Porous Silicon Structures

This invention relates to surface modification of porosified silicon (pSi) structures with poly(alkylene) glycols for the purpose of controlled degradation of the silicon matrix and tailored release of encapsulated substances for biomedical applications. The pSi structures are currently used in diverse biomedical applications including bio-molecular screening, optical bio-sensoring, and drug delivery by means of injectable/orally administered carriers and implantable devices. The size of the pores and the surface chemistry of the pSi structure can be controlled during the microfabrication process and thereafter. A fine regulation of the degradation kinetics of mesoporous silicon structures is of fundamental importance. Polyethylene glycols (PEGs) represent the major category of surface modifying agents used in classical drug delivery systems and in pharmaceutical dosage forms. PEGylation enables avoidance of RES uptake, thus prolonging circulation time of intravenously injectable nanovectors. PEG molecules demonstrate little toxicity and immunogenicity, and are cleared from the body through the urine (molecular weight, MW less than 30 kDa) or in the feces (MW greater than 30kDa). The invention focuses on the possibility of finely tuning the degradation kinetics of the pSi nanovectors and other structures through surface conjugation of PEGs with various backbone lengths/MWs. To prove the concept, pSi nanovectors were covalently conjugated to seven PEGs with MW from 245 to 5,000 Da and their degradation kinetics in physiologically relevant media (phosphate buffer saline, PBS pH7.4, and fetal bovine serum) was assessed by the elemental analysis of the Si using inductive coupled plasma atomic emission spectroscopy (ICP-AES). The conjugation of the PEG with lowest MW to the nanovectors surface did not induce any change in the degradation kinetics in serum, but inhibited degradation and consequently the release of orthosilicic acid into buffer. When PEGs with the longer chains were evaluated, Si mass loss from the nanovectors was slowed down, and the PEGylated structures were almost fully degraded within 18 24 hours in serum and within 48 hours in PBS. The most dramatic effect was observed for high MW PEGs 3,400 and 5,000 Da, which prominently inhibited the degradation of the systems, with complete degradation achieved only after four days. For these PEGs, during the early stages of the degradation, there was a lag period of little or no Si mass loss from the nanovector. The obtained profiles were in agreement with the erosion of the nanovector surface as observed by scanning electron microscopy.

Vilentchouk, Biana Godin↗

NASA NTRS1996

Transmembrane transport of peptide type compounds: prospects for oral delivery

Synthesis and delivery of potential therapeutic peptides and peptidomimetic compounds has been the focus of intense research over the last 10 years. While it is widely recognized that numerous limitations apply to oral delivery of peptides, some of the limiting factors have been addressed and their mechanisms elucidated, which has lead to promising strategies. This article will briefly summarize the challenges, results and current approaches of oral peptide delivery and give some insight on future strategies. The barriers determining peptide bioavailability after oral administration are intestinal membrane permability, size limitations, intestinal and hepatic metabolism and in some cases solubility limitations. Poor membrane permeabilities of hydrophilic peptides might be overcome by structurally modifying the compounds, thus increasing their membrane partition characteristics and/or their affinity to carrier proteins. Another approach is the site-specific delivery of the peptide to the most permeable parts of the intestine. The current view on size limitation for oral drug delivery has neglected partition considerations. Recent studies suggest that compounds with a molecular weight up to 4000 might be significantly absorbed, assuming appropriate partition behavior and stability. Metabolism, probably the most significant factor in the absorption fate of peptides, might be controlled by coadministration of competitive enzyme inhibitors, structural modifications and administration of the compound as a well absorbed prodrug that is converted into the therapeutically active agent after its absorption. For some peptides poor solubility might present a limitation to oral absorption, an issue that has been addressed by mechanistically defining and therefore improving formulation parameters. Effective oral peptide delivery requires further development in understanding these complex mechanisms in order to maximize the therapeutic potential of this class of compounds.

NASA Discipline Regulatory Physiology↗

NASA NTRS1982

Synthesis of adriamycin-coupled polyglutaraldehyde microspheres and evaluation of their cytostatic activity

Adriamycin was coupled to polyglutaraldehyde microspheres having an average diameter of 4500 A. The coupled microspheres remained stable during incubation with cells. Full cytostatic activity was observed when the coupled adriamycin was tested with murine or human leukemia and murine sarcoma cell lines. A 10-fold increase in sensitivity was obtained with drug-resistant human leukemia cell lines. Repeated use of the coupled microspheres in the cytostatic assays did not decrease their activity, indicating that these complexes can be recycled. The results suggest that coupled adriamycin sufficiently perturbs the plasma membrane to lead to cytostatic activity. It is proposed that this mode of drug delivery provides multiple and repetitious sites for drug-cell interactions. In addition, the drug-polymer complexes may overcome those forms of resistance that are the result of decreased drug binding at the cell surface.

Tokes, Z. A.↗

NASA NTRS2011

Method and Apparatus for Forming Nanodroplets

This innovation uses partially miscible fluids to form nano- and microdroplets in a microfluidic droplet generator system. Droplet generators fabricated in PDMS (polydimethylsiloxane) are currently being used to fabricate engineered nanoparticles and microparticles. These droplet generators were first demonstrated in a T-junction configuration, followed by a cross-flow configuration. All of these generating devices have used immiscible fluids, such as oil and water. This immiscible fluid system can produce mono-dispersed distributions of droplets and articles with sizes ranging from a few hundred nanometers to a few hundred microns. For applications such as drug delivery, the ability to encapsulate aqueous solutions of drugs within particles formed from the droplets is desirable. Of particular interest are non-polar solvents that can dissolve lipids for the formation of liposomes in the droplet generators. Such fluids include ether, cyclohexane, butanol, and ethyl acetate. Ethyl acetate is of particular interest for two reasons. It is relatively nontoxic and it is formed from ether and acetic acid, and maybe broken down into its constituents at relatively low concentrations.

Ackley, Donald↗

NASA NTRS2008

Pharmacy in a New Frontier - The First Five Years at the Johnson Space Center Pharmacy

A poster entitled "Space Medicine - A New Role for Clinical Pharmacists" was presented in December 2001 highlighting an up-and-coming role for pharmacists at the Johnson Space Center (JSC) in Houston, Texas. Since that time, the operational need for the pharmacy profession has expanded with the administration s decision to open a pharmacy on site at JSC to complement the care provided by the Flight Medicine and Occupational Medicine Clinics. The JSC Pharmacy is a hybrid of traditional retail and hospital pharmacy and is compliant with the ambulatory care standards set forth by the Joint Commission. The primary charge for the pharmacy is to provide medication management for JSC. In addition to providing ambulatory care for both clinics, the pharmacists also practice space medicine. A pharmacist had been involved in the packing of both the Space Shuttle and International Space Station Medical Kits before the JSC Pharmacy was established; however, the role of the pharmacist in packing medical kits has grown. The pharmacists are now full members of the operations team providing consultation for new drug delivery systems, regulations, and patient safety issues. As the space crews become more international, so does the drug information provided by the pharmacists. This presentation will review the journey of the JSC Pharmacy as it celebrated its five year anniversary in April of 2008. The implementation of the pharmacy, challenges to the incorporation of the pharmacy into an existing health-care system, and the current responsibilities of a pharmacist at the Johnson Space Center will be discussed.

Bayuse, Tina↗

NASA NTRS1998

Use of Novel Light Sources and Melatonin Delivery Systems in the Maintenance of Temporal Organization of Physiological and Behavioral Circadian Rhythms

The synchronization of physiological and behavioral rhythms are controlled by an endogenous biological clock. It is generally accepted that environmental lighting is the strongest entrainer of this clock. The pineal gland is an important physiological transducer of environmental lighting via systemic melatonin secretion. We have used a novel light source using light emitting diode (LED) technology to entrain circadian rhythms in rats, and propose a novel percutaneous exogenous melatonin delivery system to entrain rat rhythms. We used 5 groups of Sprague-Dawley rats (175-350 g; N = 8/group) and showed normal entrainment of gross locomotor activity, feeding, and drinking circadian rhythms at light intensities varying from 80 lux to 0.1 lux (22.4 to 0.03 sq cm). To improve the delivery of melatonin across the skin stratum corneum it was formulated in a suitable vehicle in a transdermal drug delivery system. Various saturated and unsaturated fatty acids were used E, akin penetration enhancers. Our best vehicle formulation was achieved with a combination-of ethano1:water (60:40) along with 5% oleic acid as the enhancer. This formulation mixture was studied using Franz diffusion cell (0.636 sq cm diffusional area) and 1 cu cm dorsal skin isolated from Sprague Dawley rats. Our results showed that oleic acid in combination with the water ethanol mixture improved the flux of melatonin by more than 18 fold. The lag time for melatonin permeation was 2-3 hrs and the peak concentrations were achieved in 8-10 hrs. Our approaches in the future will involve the use of our transdermal melatonin delivery system and under the influence of LED light and microgravity.

Winget, C. M.↗

NASA NTRS1990

Pharmacokinetics and Pharmacodynamics in Space

The Pharmacokinetics and Pharmacodynamics Panel met on 29-30 Aug. 1988 at the Lunar and Planetary Institute in Houston, Texas to discuss pharmacokinetic and pharmacodynamic implications of space flight and make recommendations for operational and research strategies. Based on the knowledge available on the physiological changes that occur during space flight, the dependence of pharmacokinetics on physiological factors, and the therapeutic requirements for future space missions, the panel made several recommendations for research. It was suggested that using medications available with a large (wide) therapeutic window will avoid unforeseen therapeutic consequences during flight. The sequence for conducting research was outlined as follows: (1) identify ground-based simulation models (e.g., antiorthostatic bed rest) for conducting pharmacokinetic and pharmacodynamic research; (2) estimate parametric changes in these models using pharmacologic agents that have different pharmacokinetic characteristics and a narrow therapeutic index; (3) verify these findings during flight; and (4) develop and identify appropriate and effective drug delivery systems, dosage forms, and regimens. The panel recommended gaining a thorough understanding of the pharmacokinetic deviations of medications that have a narrow therapeutic index (e.g. cardiovascular drugs and sedative hypnotics) in order to ensure safe and effective treatment during flight with these agents. It was also suggested that basic information on physiological factors such as organ blood flow, protein composition and binding, tissue distribution, and metabolism by hepatic enzymes must be accumulated by conducting ground-based animal and human studies using models of weightlessness. This information will be useful to construct and identify physiologically based pharmacokinetic models that can provide valuable information on the pharmacodynamic consequences of space flight and aid in identifying appropriate therapeutic regimens.

Putcha, Lakshmi↗

NASA NTRS2011

Solvent/Non-Solvent Sintering To Make Microsphere Scaffolds

A solvent/non-solvent sintering technique has been devised for joining polymeric microspheres to make porous matrices for use as drug-delivery devices or scaffolds that could be seeded with cells for growing tissues. Unlike traditional sintering at elevated temperature and pressure, this technique is practiced at room temperature and pressure and, therefore, does not cause thermal degradation of any drug, protein, or other biochemical with which the microspheres might be loaded to impart properties desired in a specific application. Also, properties of scaffolds made by this technique are more reproducible than are properties of comparable scaffolds made by traditional sintering. The technique involves the use of two miscible organic liquids: one that is and one that is not a solvent for the affected polymer. The polymeric microspheres are placed in a mold having the size and shape of the desired scaffold, then the solvent/non-solvent mixture is poured into the mold to fill the void volume between the microspheres, then the liquid mixture is allowed to evaporate. Some of the properties of the resulting scaffold can be tailored through choice of the proportions of the liquids and the diameter of the microspheres.

Laurencin, Cato T.↗

NASA NTRS2025

Innovative Drug Selection, Storage, and Shelf-Life Strategies for Exploration Spaceflight

Medications have been a part of space travel dating back to the Apollo missions. A safe and effective medication formulary is essential to maintaining crew health and performance during long-duration spaceflight outside of low Earth orbit (LEO). Distance from Earth creates four key operational changes that increase medical risks, including communication, resupply, crewmember health, and evacuation. The current spaceflight pharmaceutical formulary consists of medications indicated to treat a variety of anticipated medical events and healthcare needs during spaceflight, but depends on a robust consumables resupply chain, which may be strained for a Lunar, and possibly non-existent for a Mars mission. The specific medications selections for the formulary may change to optimally align with the mission, crew compliment, and spacecraft design. Medical support at long-duration exploration missions will differ from LEO missions due to mission duration, lack of consumables resupply, prolonged exposure to space radiation, and the absence of emergency medical return capability. Loss of medication resupply limits or removes the ability to replace medications that have been exhausted or degraded, potentially exacerbating the medical risk posture. To address these anticipated risks, long-duration missions must consider use of novel medical technologies, treatment modalities, and smart medical systems that offer greater crew autonomy, such as physiologically based pharmacokinetic modeling, drug repurposing, on demand drug synthesis, or wearable drug delivery / monitoring devices. Once an ideal formulary for exploration space is determined, it is essential to establish the chemical and physical stability of each medication compound, as well as its safety by identifying its degradation profiles and products. Although few studies have been conducted to provide evidence on the physicochemical stability of pharmaceuticals during space missions, the data suggests that the spaceflight environment may promote degradation in some pharmaceuticals. Formulary drug purity and efficacy should be verified by pharmaceutical stability assessments, and can be realized non-destructively, and accessed in remote environments. Non-destructive pharmaceutical analysis and statistical modelling techniques could optimize exploration spaceflight medical care by enabling early detection of suboptimal therapeutics. Likewise, novel packaging, storage strategies, and dosage form innovations are promising countermeasures to optimize pharmaceutical shelf life, purity, and quality of exploration spaceflight medications. As we prepare for more distant exploration missions, risk management planning for astronaut healthcare should include the assembly of a medication formulary that is comprehensive enough to prevent or treat anticipated medical events, remains safe and chemically stable, and retains sufficient potency to last for the duration of the mission. Following extensive review of the literature, we will present innovative formulary optimization strategies, pharmaceutical stability assessment techniques, and storage and packaging solutions that could enhance drug safety and efficacy for future exploration spaceflight missions.

Vernie R Daniels↗

NASA NTRS2014

Innovative Technologies for Efficient Pharmacotherapeutic Management in Space

Current and future Space exploration missions and extended human presence in space aboard the ISS will expose crew to risks that differ both quantitatively and qualitatively from those encountered before by space travelers and will impose an unknown risk of safety and crew health. The technology development challenges for optimizing therapeutics in space must include the development of pharmaceuticals with extended stability, optimal efficacy and bioavailability with minimal toxicity and side effects. Innovative technology development goals may include sustained/chronic delivery preventive health care products and vaccines, low-cost high‐efficiency noninvasive, non‐oral dosage forms with radio‐protective formulation matrices and dispensing technologies coupled with self‐reliant tracking technologies for quality assurance and quality control assessment. These revolutionary advances in pharmaceutical technology will assure human presence in space and healthy living on Earth. Additionally, the Joint Commission on Accreditation of Healthcare Organizations advocates the use of health information technologies to effectively execute all aspects of medication management (prescribing, dispensing, and administration). The advent of personalized medicine and highly streamlined treatment regimens stimulated interest in new technologies for medication management. Intelligent monitoring devices enhance medication accountability compliance, enable effective drug use, and offer appropriate storage and security conditions for dangerous drug and controlled substance medications in remote sites where traditional pharmacies are unavailable. These features are ideal for Exploration Medical Capabilities. This presentation will highlight current novel commercial off‐the‐shelf (COTS) intelligent medication management devices for the unique dispensing, therapeutic drug monitoring, medication tracking, and drug delivery demands of exploration space medical operations.

Putcha, Lakshmi↗

NASA NTRS1991

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.↗