Tiny Technologies Combat Nerve Agents

FORT BELVOIR, VA, UNITED STATES

08.16.2016

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

Exactly how small is a nanometer? The average human hair is 50 micrometers wide and one nanometer is 1/50,000th the width of a single strand of hair. Using nano-sized structures to combat nerve agents could lead to enormous advancements to protect warfighters.

Funded by the Defense Threat Reduction Agency’s Joint Science and Technology Office, researchers are leveraging nano science to combat organophosphonate nerve agents (OPNA) for improved warfighter safety. The efforts, managed by Dr. Brian Pate, are part of JSTO’s Nanostructured Countermeasure Platforms for Chemical Warfare Agents (NCP-CWA) program that explores enhanced delivery methods of prophylactics and therapeutics.

Currently there are no approved broad-spectrum prophylactic countermeasures available to protect the warfighter against multiple chemical threats. The JSTO portfolio aims to fill this gap with its bioscavenger program, yet the current technology has some disadvantages including high costs and dosing requirements, potential immunogenicity, and short-term stability in circulation.

In addition, the JSTO portfolio for nerve agent therapeutics currently lacks the ability to treat effects on the brain. However, the NCP-CWA program addresses the gaps in the prophylactic and therapeutic medical countermeasures program by exploring alternative platform approaches, readily tailorable to specific threat agents.

Circulatory stability is an important factor in drug design. Protein-based bioscavenger therapeutics are only available in the circulatory system for a few days while the desired target is between 10 and 60 days. Prolonged circulatory stability of a medical countermeasure would afford the warfighter advanced protection against chemical threats.

Projects in the NCP-CWA program aim to improve the circulatory stability of protein prophylactics and therapeutics via novel mechanisms that leverage nanoscale phenomena.

One such project exploits the individual’s own red blood cells (RBC). The strategy is to encapsulate the protein therapeutic in a mixture of polymers that target RBCs. Upon attachment to RBCs, the protein becomes available throughout the circulatory system to scavenge chemical threats. In addition, attachment to RBCs improves the circulatory stability of the protein.

A second key project within the program aims to promote protein stability, enhance circulatory stability and eliminate immune response using a two-pronged approach. This strategy requires attachment of the protein therapeutic to a polymer, which is then encapsulated in a gel. This conjugation/encapsulation approach was applied to two different proteins and showed up to a three-fold improvement in circulatory stability for one protein and an improvement of 25- fold for the second protein.

The encapsulated particles showed little or no immunogenicity in a study conducted in rats. The results were published in the Journal of Controlled Release, “Butyrylcholinesterase Nanocapsule as a Long Circulating Bioscavenger with Reduced Immune Response.”

A third project in JSTO’s NCP-CWA program focuses on mitigating the toxic effects of OPNAs on the brain. Nerve agents enter the brain and bind to their target resulting in seizures. Currently, there are no effective therapeutics to protect the brain prior to the onset of seizures. The NCP-CWA strategy involves formulating a small molecule drug with liposomes for intranasal drug delivery. Early results demonstrate a dramatic improvement in the survivability of mice when exposed to a nerve agent simulant.

Together, the early successes of the NCP-CWA program points the way toward more effective means to protect and treat warfighters from exposure to nerve agents. Reducing or removing the threat posed by these chemical warfare agents, among the deadliest threats faced on today’s battlefields, offers the potential to provide a new means to offset enemy capabilities to equip the U.S. with the needed edge to facilitate victory in current and future military engagements.

POC: Dr. Brian Pate [e-mail]

• Date Taken: 08.16.2016
• Date Posted: 08.16.2016 12:07
• Story ID: 207250
• Location: FORT BELVOIR, VA, US