BOSTON (1-31-12) -- Long duration, controllable drug delivery is of wide interest to medical researchers and clinicians, particularly those seeking to improve treatment for patients with chronic pain or to prevent cancer recurrence after surgery. Now a team of researchers led by Boston University Biomedical Engineer and Chemist Mark Grinstaff has developed a unique material and drug delivery mechanism that could pave the way for implants that release a drug at a designated rate for months.

The system consists of a biocompatible, highly porous, three-dimensional polymer material containing a selected drug and a volume of air that slows infiltration from surrounding water. As water seeps into the material, it displaces the air, gradually releasing the drug.

"The idea was to create a 3D material that has polymer fibers throughout and air trapped within," said Grinstaff, who developed the material in conjunction with BU biomedical engineering PhD student Stefan Yohe and Dr. Yolanda Colson, a Brigham and Women's Hospital thoracic surgeon and lung cancer specialist. "If we can slow the penetration of water into the structure, it will slow the release of the drug."

To prevent water from flooding the structure and causing an immediate release of the drug, Grinstaff and his colleagues designed the air-filled, mesh-like material to be "superhydrophobic"—so water-resistant that droplets of water barely touch the surface, forming beads similar to those that appear on a freshly waxed car. They produced the porous polymer mesh using a process called electrospinning, which overlays micron-sized fibers upon one another.

To control the rate of drug release, they adjusted chemical and physical properties of the material so that the entrapped air is loosely or tightly held. The more tightly held the air is within the structure, the harder it is for water to displace it, the slower the release, and the longer the treatment duration.

Loaded with a widely used anti-cancer drug called SN-38 in in vitro experiments, the polymer mesh and internal air pocket proved to be robust and effective against lung cancer cells in solution for more than 60 days, indicating its suitability for long-term drug delivery. Grinstaff and his collaborators next plan to conduct a series of in vivo experiments to evaluate the system's efficiency and potential clinical effectiveness—a critical preliminary step before initiating clinical trials.

Supported by the National Institutes of Health, The Wallace H. Coulter Foundation, the Center for Integration of Medicine & Innovative Technology and Boston University, this research was originally sparked by the Grinstaff group's ongoing investigation of potential therapies for recurring lung cancer, and interest in the use of new materials and procedures to deliver drugs over the course of months.

"Many researchers are advancing new drug delivery systems, and several others are designing superhydrophobic materials, but we're combining these disciplines to see if we can open up new doors and enable more effective treatments for a wide range of diseases," said Grinstaff.

The researchers detailed their novel drug delivery system in the January 16 online edition of the Journal of the American Chemical Society.

Source: Eurekalert!

WASHINGTON, Nov. 16, 2011 — A new episode in the American Chemical Society's (ACS) award-winning "Global Challenges/Chemistry Solutions" podcast series spins a real-life tale in which spider silk shows promise for overcoming a major barrier to the use of gene therapy in everyday medicine.

Penn-led team develops microelectronic device to map brain activity

PHILADELPHIA - A team of researchers co-led by the University of Pennsylvania has developed and tested a new high-resolution, ultra-thin device capable of recording brain activity from the cortical surface without having to use penetrating electrodes. The device could make possible a whole new generation of brain-computer interfaces for treating neurological and psychiatric illness and research. The work was published in Nature Neuroscience.

Children's Hospital of Philadelphia study suggests strategy to bypass defect in hemophilia, may also benefit other bleeding disorders

A genetically engineered clotting factor that controlled hemophilia in an animal study offers a novel potential treatment for human hemophilia and a broad range of other bleeding problems.

The researchers took the naturally occurring coagulation factor Xa (FXa), a protein active in blood clotting, and engineered it into a novel variant that safely controlled bleeding in mouse models of hemophilia. "Our designed variant alters the shape of FXa to make it safer and efficacious compared to the wild-type factor, but much longer-lasting in blood circulation," said study leader Rodney A. Camire, Ph.D., a hematology researcher at The Children's Hospital of Philadelphia.

"The shape of the variant FXa changes when it interacts with another clotting factor made available following an injury," added Camire. "This increases the functioning of the protein which helps stop bleeding." Camire is an associate professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania.

The study appears online today in Nature Biotechnology, and will be published in the journal's November 2011 print issue.

In hemophilia, an inherited single-gene mutation impairs a patient's ability to produce a blood-clotting protein, leading to spontaneous, sometimes life-threatening bleeding episodes. The two major forms of the disease, which occurs almost solely in males, are hemophilia A and hemophilia B, characterized by which specific clotting factor is deficient. Patients are treated with frequent infusions of clotting proteins, which are expensive and sometimes stimulate the body to produce antibodies that negate the benefits of treatment.

Roughly 20 to 30 percent of patients with hemophilia A and 5 percent of hemophilia B patients develop these inhibiting antibodies. For those patients, the conventional treatment, called "bypass therapy," is to use drugs such as factor VIIA and activated prothrombin complex concentrates (aPCCs) to restore blood clotting capability. But these agents are costly (as much as $30,000 per treatment) and not always effective. Camire added that, in the current animal study, they were able to show the variant protein is more effective at a lower dose than FVIIa.

The range of options for hemophilia patients could improve if the study results in animals were to be duplicated in humans. "The variant we have developed puts FXa back on the table as a possible therapeutic agent," said Camire. Naturally occurring (wild-type) FXa, due to its particular shape, is not useful as a therapy because normal biological processes shut down its functioning very quickly.

By custom-designing a different shape for the FXa protein, Camire's study team gives it a longer period of activity, while limiting its ability to engage in unwanted biochemical reactions, such as triggering excessive clotting. "This potentially could lead to a new class of bypass therapy for hemophilia, but acting further downstream in the clot-forming pathway than existing treatments," said Camire, who has investigated the biochemistry of blood-clotting proteins for more than a decade.

When infused into mice with hemophilia, the FXa variant reduced blood loss after injury, as it safely restored blood clotting ability. Further studies are necessary in large animal models to determine whether this approach can become a clinical treatment for hemophilia patients who have developed inhibitors, or even more broadly as a drug for uncontrolled bleeding in other clinical situations.

Funding support for this research came from the National Institutes of Health, Pfizer Inc., and the National Hemophilia Foundation. The first author of the study was Lacramioara Ivanciu, Ph.D., of The Children's Hospital of Philadelphia. Other co-authors with Camire were from Children's Hospital, Pfizer Inc., and the Perelman School of Medicine of the University of Pennsylvania.

Geneticists at Emory University School of Medicine have demonstrated a method that enables the routine amplification of all the genes on the X chromosome.

Researchers from the National Institute of Standards and Technology (NIST) and University of Colorado Boulder (CU) have developed a low-power microchip that uses a combination of microfluidics and magnetic switches to trap and transport magnetic beads.

Promega Corporation announced today that it has launched GoTaq(r) 1-Step RT-qPCR System for quantitative analysis of RNA.

Scientists at Universidad Carlos III de Madrid (UC3M -- Carlos III University) are participating in research to study how to make use of the potential for auto regeneration of stem skills from skin, in order to create, in the laboratory, a patient's entire cutaneous surface by means of a combination of biological engineering and tissue engineering techniques.

Scientists have improved upon their own previous world-best efforts to pluck out just the right stem cells to address the brain problem at the core of multiple sclerosis and a large number of rare, fatal children’s diseases.

U.S. Naval Research Laboratory researchers Dr. Sean J. Hart, Dr. Colin G. Hebert and Mr. Alex Terray have developed a laser-based analysis method that can detect optical pressure differences between populations or classes of blood cells that does not rely on prior knowledge, antibodies, or fluorescent labels for discrimination.