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At least 55 records · Page 3

Optimizing Surfactant Templating of Yttria-Stabilized Zirconia Aerogels for High-Temperature Applications: Effect of Anionic and Nonionic Surfactant

Aerogels, mesoporous materials with extreme material properties including high specific surface area, low density, and low thermal conductivity, can be useful for applications including catalysis, sorption media, and drug delivery. The low thermal conductivity and high surface area of aerogels makes them advantageous as thermal management systems, specifically for aerospace or aeronautics applications. However, the pore collapse and subsequent surface area decrease of aerogels following exposure to high temperatures must be mitigated to allow aerogels to be effectively used in thermal management applications. This work investigates the anionic surfactant sodium dodecyl sulfate (SDS) and the nonionic surfactant Pluronic® P-123 as surfactant templates in yttria-stabilized zirconia (YSZ) aerogels. By utilizing surfactant templates, known to influence pore structure, it is anticipated that sintering and densification of the aerogels following high-temperature exposure will be mitigated. It was determined that the addition of SDS and P-123 increased the surface area and pore volume of as-dried aerogels and suppressed crystallite growth at high temperatures. However, the impact of surfactant templates on the surface area and pore volume of heat-treated aerogels was negligible, potentially due to low concentrations of surfactant and the removal of the surfactant following high-temperature exposure.

Yttria-stabilized zirconia aerogels↗

Exploring the Complexities of Drug Formulation Selection, Storage, and Shelf-Life for Exploration Spaceflight

Medications have been a part of space travel dating back as far as the Apollo missions. Currently, medical kits aboard the ISS contain medications and supplies to help crew members cope with a variety of possible medical events. NASA reported that 1,867 medical events occurred from 1981 to 1998 on space shuttle flights, STS-1 to STS-89; 498 out of the 508 crewmembers on those flights reported experiencing a medical event other than space motion sickness. In 2000, the Institute of Medicine (IOM) convened a committee of experts, Committee on Creating a Vision for Space Medicine during Travel beyond Earth Orbit, to examine the issues surrounding astronaut health and safety for long duration space missions. The primary theme of the committee’s final report is that there is not enough known about the risks to human health during long-duration missions beyond Earth’s orbit and ways to effectively mitigate those risks in an environment of deep space. In 2014, the IOM convened the Committee on Ethics Principles and Guidelines for Health Standards for Long Duration and Exploration Spaceflights and released a report emphasizing the importance of prevention, mitigation, and treatment of major risks to human health during exploration spaceflight. NASA’s Human Research Program has organized five distinct categories of spaceflight hazards summarized by the acronym “RIDGE” (Space Radiation, Isolation and Confinement, Distance from Earth, Gravity fields, and Hostile/Closed Environments) that astronauts may encounter during exploration spaceflight. From those hazards, NASA further derived 30 of the most critical human health and performance risks, including limits to medical care resulting from pharmaceutical degradation. As we prepare for more distant exploration missions to Mars and beyond, 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. The present editorial will summarize the current state of knowledge regarding 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.

drug degradation risk assessment↗

Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

Putcha, Lakshmi↗

Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers

The present work utilizes electrospinning to fabricate synthetic polymer/DNA composite scaffolds for therapeutic application in gene delivery for tissue engineering. The scaffolds are non-woven, nano-fibered, membranous structures composed predominantly of poly(lactide-co-glycolide) (PLGA) random copolymer and a poly(D,L-lactide)-poly(ethylene glycol) (PLA-PEG) block copolymer. Release of plasmid DNA from the scaffolds was sustained over a 20-day study period, with maximum release occurring at approximately 2 h. Cumulative release profiles indicated amounts released were approximately 68-80% of the initially loaded DNA. Variations in the PLGA to PLA-PEG block copolymer ratio vastly affected the overall structural morphology, as well as both the rate and efficiency of DNA release. Results indicated that DNA released directly from these electrospun scaffolds was indeed intact, capable of cellular transfection, and successfully encoded the protein beta-galactosidase. When tested under tensile loads, the electrospun polymer/DNA composite scaffolds exhibited tensile moduli of approximately 35 MPa, with approximately 45% strain initially. These values approximate those of skin and cartilage. Taken together, this work represents the first successful demonstration of plasmid DNA incorporation into a polymer scaffold using electrospinning.

Non-NASA Center↗

Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent

PURPOSE: The objective was to investigate the ability of a glycosteroid (TC002) to increase the oral bioavailability of gentamicin. METHODS: Admixtures of gentamicin and TC002 were administered to the rat ileum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. 3H-TC002 was injected via externalized cannulas into rat ileum or jejunum, or PO and its distribution and elimination was determined. The metabolism of TC002 in rats was evaluated by solid phase extraction and HPLC analysis of plasma, urine and feces following oral or intestinal administration. RESULTS: The bioavailability of gentamicin was substantially increased in the presence of TC002 in both rats and dogs. The level of absorption was dependent on the concentration of TC002 and site of administration. Greatest absorption occurred following ileal orjejunal administration. TC002 was significantly more efficacious than sodium taurocholate, but similar in cytotoxicity. TC002 remained primarily in the GI tract following oral or intestinal administration and cleared rapidly from the body. It was only partly metabolized in the GI tract, but was rapidly and completely converted to its metabolite in plasma and urine. CONCLUSIONS: TC002 shows promise as a new drug transport agent for promoting intestinal absorption of polar molecules such as gentamicin.

Non-NASA Center↗

Code Blue on Orbit: Treating Cardiac Arrest on the ISS

As a result of the Columbia tragedy on February 1,2003, the International Space Station (ISS) crew size has been temporarily reduced from three to two. This change forces adaptations in many operational procedures used by the crew, including medical protocols which were designed for scenarios involving one casualty and two caregivers. The Office of Space Medicine directed that the procedure for the resuscitation of a crewmember in cardiac arrest be rewritten for use by a single care provider. Methods: Adaptation of this procedure made use of current American Heart Association Advanced Cardiac Life Support (ACLS) procedures and reflects necessary compromises between the realities of the operational environment and prompt provision of medical care. Results: Numerous changes were incorporated due to the diminution in available personnel, including substitution of endotracheal rather than intravenous delivery of drugs, more rapid defibrillation, addition of a precordial thump, removal of transcutaneous pacing, streamlining of procedural steps, and clarification of termination criteria. Discussion: The on-orbit care available to the ISS crewmembers is constrained by numerous factors, including crew medical training, minimal medical assets, limited air/ground communication , and a single caregiver for the foreseeable future. All of these combine to make a successful resuscitation unlikely, however, this procedure must ultimately deal with not only the patient's welfare, but also that of the caregiver, the mission, and the program.

Bacal, Kira↗

Implantable Wireless MEMS Sensors for Medical Uses

Sensors designed and fabricated according to the principles of microelectromechanical systems (MEMS) are being developed for several medical applications in outer space and on Earth. The designs of these sensors are based on a core design family of pressure sensors, small enough to fit into the eye of a needle, that are fabricated by a "dissolved wafer" process. The sensors are expected to be implantable, batteryless, and wireless. They would be both powered and interrogated by hand-held radio transceivers from distances up to about 6 in. (about 15 cm). One type of sensor would be used to measure blood pressure, particularly for congestive heart failure. Another type would be used to monitor fluids in patients who have hydrocephalus (high brain pressure). Still other types would be used to detect errors in delivery of drugs and to help patients having congestive heart failure.

Chimbayo, Alexander↗

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.↗

Quality Control Method for a Micro-Nano-Channel Microfabricated Device

A variety of silicon-fabricated devices is used in medical applications such as drug and cell delivery, and DNA and protein separation and analysis. When a fluidic device inlet is connected to a compressed gas reservoir, and the outlet is at a lower pressure, a gas flow occurs through the membrane toward the outside. The method relies on the measurement of the gas pressure over the elapsed time inside the upstream and downstream environments. By knowing the volume of the upstream reservoir, the gas flow rate through the membrane over the pressure drop can be calculated. This quality control method consists of measuring the gas flow through a device and comparing the results with a standard curve, which can be obtained by testing standard devices. Standard devices can be selected through a variety of techniques, both destructive and nondestructive, such as SEM, AFM, and standard particle filtration.

Grattoni, Alessandro↗

Rodent Research on the International Space Station - A Look Forward

Rodent Research on the International Space Station (ISS) is one of the highest priority science activities being supported by NASA and is planned for up to two flights per year. The first Rodent Research flight, Rodent Research-1 (RR-1) validates the hardware and basic science operations (dissections and tissue preservation). Subsequent flights will add new capabilities to support rodent research on the ISS. RR-1 will validate the following capabilities: animal husbandry for up to 30 days, video downlink to support animal health checks and scientific analysis, on-orbit dissections, sample preservation in RNA. Later and formalin, sample transfer from formalin to ethanol (hindlimbs), rapid cool-down and subsequent freezing at -80 of tissues and carcasses, sample return and recovery. RR-2, scheduled for SpX-6 (Winter 20142015) will add the following capabilities: animal husbandry for up to 60 days, RFID chip reader for individual animal identification, water refill and food replenishment, anesthesia and recovery, bone densitometry, blood collection (via cardiac puncture), blood separation via centrifugation, soft tissue fixation in formalin with transfer to ethanol, and delivery of injectable drugs that require frozen storage prior to use. Additional capabilities are also planned for future flights and these include but are not limited to male mice, live animal return, and the development of experiment unique equipment to support science requirements for principal investigators that are selected for flight. In addition to the hardware capabilities to support rodent research the Crew Office has implemented a training program in generic rodent skills for all USOS crew members during their pre-assignment training rotation. This class includes training in general animal handling, euthanasia, injections, and dissections. The dissection portion of this training focuses on the dissection of the spleen, liver, kidney with adrenals, brain, eyes, and hindlimbs. By achieving and maintaining proficiency in these basic skills as part of the nominal astronaut training curriculum this allows the rodent research program to focus the mission specific crew training on scientific requirements of research and operations flow.

Experimental capabilities↗

Fluid Mechanics of Capillary-Elastic Instabilities in Microgravity Environment

The aim of this project is to investigate the closure and reopening of lung airways due to surface tension forces, coupled with airway elasticity. Airways are liquid-lined, flexible tubes and closure of airways can occur by a Rayleigh instability of the liquid lining, or an instability of the elastic support for the airway as the surface tension of the air-liquid interface pulls the tube shut, or both. Regardless of the mechanism, the airway is closed because the liquid lining has created a plug that prevents axial gas exchange. In the microgravity environment, surface tension forces dominate lung mechanics and would lead to more prevalent, and more uniformly distributed air-way closure, thereby creating a potential for respiratory problems for astronauts. Once closed the primary option for reopening an airway is by deep inspiration. This maneuver will pull the flexible airways open and force the liquid plug to flow distally by the incoming air stream. Airway reopening depends to a large extent on this plug flow and how it may lead to plug rupture to regain the continuity of gas between the environment and the alveoli. In addition to mathematical modeling of plug flows in liquid-lined, flexible tubes, this work has involved benchtop studies of propagating liquid plugs down tube networks that mimic the human airway tree. We have extended the work to involve animal models of liquid plug propagation in rat lungs. The liquid is radio-opaque and x-ray video imaging is used to ascertain the movement and distribution of the liquid plugs so that comparisons to theory may be made. This research has other uses, such as the delivery of liquids or drugs into the lung that may be used for surfactant replacement therapy or for liquid ventilation.

Grotberg, James B.↗

Advances in Nanotechnology for Efficacious and Stable Formulation Development

Current operational medical kits aboard the International Space Station (ISS) include an array of medications intended for the treatment of minor ambulatory care symptoms, first aid, and basic life support. All medications contained in the flight kits are commercially available off-the-shelf formulations used for treatment of illnesses on Earth. However, transport and stowage of supplies including medications for space missions are exposed to adverse environmental conditions and extended shelf-life demands. Proposed missions to Mars and near-Earth objects such as asteroid 1999 AO10 will present crew health risk that is different both quantitatively and qualitatively from those encountered on ISS missions. Few drug options are available at the present time for mitigation of crew health risk of planned space exploration missions. Alternatives to standard oral formulations that include sustained and targeted delivery technologies for preventive healthcare in space will be a welcome addition to the space formulary and may include controlled release topical, sub-cutaneous, intranasal and inhalation dosage forms. An example of such a technology development endeavor can be nanotechnology-based multi-stage drug cocktail and vaccine delivery systems. Nanostructures also have the ability to protect drugs encapsulated within them from physiologic degradation, target their delivery with sustained release and are suitable for per oral routes of administration. The use of nanostructures such as polymeric nanoparticles offers a non-invasive approach for penetrating the blood brain barrier. Finally, nanotechnology offers great potential for the development of safe and efficacious drug delivery systems for preventive health care in space and on Earth.

Putcha, Lakshimi↗

The Pathway to a Safe and Effective Medication Formulary for Exploration Spaceflight

PURPOSE: Exploration space missions pose several challenges to providing a comprehensive medication formulary designed to accommodate the size and space limitations of the spacecraft; while addressing the individual medications needs and preferences of the Crew; the negative outcome of a degrading inventory over time, the inability to resupply before expiration dates; and the need to properly forecast the best possible medication candidates to treat conditions that will occur in the future. METHODS: The Pharmacotherapeutics Discipline has partnered with the Exploration Medical Capabilities (ExMC) Element to develop and propose a research pathway that is comprehensively focused on evidence-based models and theories, as well as on new diagnostic tools and treatments or preventive measures aimed at closure of the Med02 “Pharmacy” Gap; defined in the Human Research Program’s (HRP) risk-based research strategy. The Med02 Gap promotes the challenge to identify a strategy to ensure that medications used to treat medical conditions during exploration space missions are available, safe, and effective. It is abundantly clear that pharmaceutical intervention is an essential component of risk management planning for astronaut healthcare during exploration space. However, the quandary still remains of how to assemble a formulary that is comprehensive enough to prevent or treat anticipated medical events; and is also chemically stable, safe, and robust enough to have sufficient potency to last for the duration of an exploration space mission. In cases where that is not possible, addressing this Gap requires exploration of novel drug development techniques, dosage forms, and dosage delivery platforms that enhance chemical stability as well as therapeutic effectiveness. RESULTS: The proposed research pathway outlines the steps, processes, procedures, and a research portfolio aimed at identifying a capability that will provide a safe and effective pharmacy for any specific exploration Design Reference Mission (DRM). The proposed approach to building this research portfolio is to seek research projects that concentrate on four major focus areas; (1) Formulary selection, (2) Formulary potency and shelf life, (3) Formulary safety and toxicity, and (4) Novel technology and innovation such as portable real-time chemical analysis innovative drug therapies and dosage and delivery platforms. CONCLUSION: The research pathway has been completed and presented to the HRP. In spring 2017, it is scheduled to be reviewed by a panel of pharmaceutical and clinical experts that will evaluate the scientific merit and operational feasibility of the research pathway, as well as make suggestions for any warranted additions or improvements. Once finalized, the ExMC Element will proceed with the execution of this research pathway with the goal of gathering as much data, and learning as much as possible, to provide a safe and effective pharmaceutical formulary for use during exploration missions.

Daniels, V. R.↗

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↗

An update on Lab Rover: A hospital material transporter

The development of a hospital material transporter, 'Lab Rover', is described. Conventional material transport now utilizes people power, push carts, pneumatic tubes and tracked vehicles. Hospitals are faced with enormous pressure to reduce operating costs. Cyberotics, Inc. developed an Autonomous Intelligent Vehicle (AIV). This battery operated service robot was designed specifically for health care institutions. Applications for the AIV include distribution of clinical lab samples, pharmacy drugs, administrative records, x-ray distribution, meal tray delivery, and certain emergency room applications. The first AIV was installed at Lahey Clinic in Burlington, Mass. Lab Rover was beta tested for one year and has been 'on line' for an additional 2 years.

Mattaboni, Paul↗

Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

Putcha, Lakshmi↗

Monitoring Location and Angular Orientation of a Pill

A mobile pill transmitter system moves through, or adjacent to, one or more organs in an animal or human body, while transmitting signals from its present location and/or present angular orientation. The system also provides signals from which the present roll angle of the pill, about a selected axis, can be determined. When the location coordinates angular orientation and the roll angle of the pill are within selected ranges, an aperture on the pill container releases a selected chemical into, or onto, the body. Optionally, the pill, as it moves, provides a sequence of visually perceptible images. The times for image formation may correspond to times at which the pill transmitter system location or image satisfies one of at least four criteria. This invention provides and supplies an algorithm for exact determination of location coordinates and angular orientation coordinates for a mobile pill transmitter (PT), or other similar device that is introduced into, and moves within, a GI tract of a human or animal body. A set of as many as eight nonlinear equations has been developed and applied, relating propagation of a wireless signal between either two, three, or more transmitting antennas located on the PT, to four or more non-coplanar receiving antennas located on a signal receiver appliance worn by the user. The equations are solved exactly, without approximations or iterations, and are applied in several environments: (1) association of a visual image, transmitted by the PT at each of a second sequence of times, with a PT location and PT angular orientation at that time; (2) determination of a position within the body at which a drug or chemical substance or other treatment is to be delivered to a selected portion of the body; (3) monitoring, after delivery, of the effect(s) of administration of the treatment; and (4) determination of one or more positions within the body where provision and examination of a finer-scale image is warranted.

Schipper, John F.↗

Liquid-Spray Formulation Of Scopolamine

Scopolamine, fast-acting anticholinergic drug, formulated into drops administered intranasally. Formulation very useful for people who need immediate relief from motion sickness, and they can administer it to themselves. Also used in other clinical situations in which fast-acting anticholinergic medication required. Modified into such other forms as gel preparation, aqueous-base ointment, or aerosol spray or mist; also dispensed in metered-dose delivery system.

Putcha, Lakshmi↗