Biosciences, Bioengineering, and Pharmaceutical Research

Institute staff members are involved in a variety of programs related to the diagnosis and treatment of disease, including environmental and biomedical science, biomaterials and medical device development, bioengineering research, and pharmaceutical research. Also, as a member of the Southwest Research Consortium, SwRI conducts cooperative programs with other San Antonio Organizations — the University of Texas Health Science Center at San Antonio (UTHSCSA), the Southwest Foundation for Biomedical Research, the University of Texas at San Antonio, and Trinity University. Institute scientists also participate in the Center for Cell Regulation and Enhancement of the Biology/Biomaterials Interface at UTHSCSA.

The performance of preclinical efficacy and safety investigations, including pharmacokinetic studies, for biotechnology products continues to be a rapidly growing activity at the Institute. These studies, which meet Good Laboratory Practice standards, provide data for use by the U.S. Food and Drug Administration in the testing of new drugs in humans. Historically, preclinical investigations have used rodents and dogs as the primary research subjects; however, many new drugs, as well as new materials used in medical devices, are designed specifically to be compatible with human biochemistry and immunology. Consequently, the Institute increasingly uses nonhuman primates as the biomedical model that most closely resembles human physiology.

The Institute's complete adult and neonatal intensive care unit and a fully equipped operating suite support animal studies to evaluate the safety and efficacy of new medical devices.

In addition to conventional dosing studies, SwRI conducts toxicology investigations using unconventional drug administration routes. Studies were completed in 1995 using intradermal delivery and intracerebroventricular administration through an indwelling cannula. SwRI used magnetic resonance imaging (MRI) and computerized axial tomographic (CAT) scans to support the brain-delivery study.

SwRI accelerated progress toward a cure for diabetes by demonstrating that insulin-producing cells taken from pig pancreas can survive in a nonhuman primate. Using a novel, proprietary encapsulating device, the cells were placed in baboons. Further studies will include testing the device for clinical effectiveness in baboons with induced or naturally occurring diabetes.

With NASA sponsorship, Institute scientists investigated the risk of cancer caused by radiation exposure in deep space. Laboratory rats were exposed to high-energy proton radiation, similar to the solar flare radiation that astronauts would encounter during planetary travel or extended orbiting space station assignments. The results indicate a sensitivity of the tissues of the head and neck to the carcinogenic effects of high-energy proton radiation. The results will help NASA better assess risks to humans on extended space missions.

Stress, fatigue, sleeplessness, and other discomforts that result as the body adapts to microgravity during space flight can adversely affect an astronaut's ability to function. The Institute is working with NASA scientists to develop a portable cognitive activity monitor to be used by astronauts in space. The pocket-sized electronic device administers a series of tests that measure functions such as visual activity, reaction time, and motor coordination. The results will be used by NASA scientists and physicians to monitor the performance of astronauts.

In a project for the Advanced Research Projects Agency, the Institute is developing a trauma patient simulator for use in the U.S. Army's Life Support for Trauma and Transport device. To simulate a patient, SwRI developed a hybrid mathematical and neural network model of the cardiovascular system to predict changes in heart rate, blood pressure, blood values, and cardiac output based on blood loss and fluid administration. A system is also being developed to automate the selection of fluid resuscitation treatment for a trauma victim, based on the model's predictions of the patient's status.

Continuing its long history in the development of automatic blood pressure monitoring systems, SwRI recently developed a noninvasive system that continuously monitors blood pressure and produces a blood pressure waveform, a signal that was available previously only by inserting a catheter inside an artery. The device is being improved with a waveform analysis system that processes the blood pressure waveform for indications of changes in clinical status. The combined methodology will provide safer, more informative ways to monitor critical care parameters.

Medical monitoring and diagnostic devices increasingly use optical techniques for fast, accurate physiological measurement and assessment. SwRI is using its expertise in optics, optical fibers, algorithms for physiological monitoring, medical electronics, computer software, and microprocessors to develop integrated monitoring systems for hospital critical care units. These systems track the amount of blood pumped by the heart, the levels of oxygen and carbon dioxide in the blood, and the general performance of the cardiovascular and respiratory systems. Institute capabilities are also being applied in the new field of optical biopsy, in which an assessment of an organ's performance is made by shining light on it and analyzing the properties of the reflected light.

The Institute is applying its experience in the development of software for industrial and military clients to independent verification and validation of software for medical devices. In 1995, SwRI validated the software for a cardiac catheterization system, a pulmonary function analyzer, a clinical spreadsheet used to collect physiological data, a continuous arterial blood gas monitor, a cardiac output computer, and an oximeter. In validating software, SwRI uses its own software development methodology, which has become the standard for several medical device companies.

A device to hold the head during magnetic resonance imaging or computerized axial tomographic scan imaging of the brain is shown here in a CAD software rendering. The software allows the brain and holder to be imaged simultaneously, enabling neurosurgeons to accurately position their instruments. A prototype headholder was produced by stereolithography, which used the CAD files and lasers to polymerize the engineering plastic and produce the final shaped parts directly from the computer file.

Rapid electrical and mechanical design prototyping capabilities grew during 1995. Rapid prototyping depends, in part, on the use of computer workstations with sophisticated design software to simulate the function and appearance of devices without first going through expensive fabrication processes. For example, mechanical design engineers developed a non-metallic system that holds the head during MRI or CAT scan imaging of the brain. The prototype was developed using CAD software and fabricated using stereolithography. The software allows the brain and the holder to be imaged simultaneously, enabling neurosurgeons to accurately position their instruments.

A model for the development of secondary cataracts, which form in some patients following removal of the natural ocular lens as a result of cataracts, has been developed at the Institute in collaboration with UTHSCSA and an independent consultant. The model is being used to study epithelial cell proliferation on lens capsules and implanted intraocular lenses, and to determine the effectiveness of new drug applications and delivery systems to prevent cell proliferation, thus blocking secondary cataract formation.

Institute scientists investigated the absorption of nutrients and oral drugs contained in different hydrogel formulations to reduce unwanted side effects and to enhance drug release and absorption. Two bioanalytical assays were developed and validated to support drug release and absorption analyses in plasma and urine, and pharmacokinetic analyses were used to determine the effectiveness of more than 20 hydrogel formulations.

Sustained and controlled release formulations using microencapsulation and specialty coating technologies were applied to preventive antibiotic and hormone delivery systems for veterinary products. The Institute developed the formulations and tested them in vitro over a three-month period. Results correlated well with subsequent in vivo release profiles. The data are being used to develop second-generation formulations that will provide at least three months of continuous release.

The application of biodegradable microparticles as carriers for oral vaccines, to elicit a mucosal immune response after ingestion, has been expanded to include potential anti-AIDS vaccines. In close collaboration with a client, SwRI is developing the microparticles and conducting complete physical-chemical evaluations. The client is testing the effectiveness of the microparticles in animal models.

1995 Annual Report SwRI Home