Tag Archives: snake venom

Snake venom as a healing agent in hydrogels

The Brazilian lancehead is one of several South American pit vipers that produce venom that has proven to be a powerful blood coagulant. Scientists at Rice University have combined a derivative of the venom with their injectable hydrogels to create a material that can quickly stop bleeding and protect wounds, even in patients who take anti-coagulant medications. (Credit: Photo by Greg Hume via Wikipedia)

The Brazilian lancehead is one of several South American pit vipers that produce venom that has proven to be a powerful blood coagulant. Scientists at Rice University have combined a derivative of the venom with their injectable hydrogels to create a material that can quickly stop bleeding and protect wounds, even in patients who take anti-coagulant medications. (Credit: Photo by Greg Hume via Wikipedia)

Mesmerizing and beautiful in their way, venomous snakes are healers, as well as, killers. An Oct. 27, 2015 news item on Azonano describes a new healing use for their venom,

A nanofiber hydrogel infused with snake venom may be the best material to stop bleeding quickly, according to Rice University scientists.

The hydrogel called SB50 incorporates batroxobin, a venom produced by two species of South American pit viper. It can be injected as a liquid and quickly turns into a gel that conforms to the site of a wound, keeping it closed, and promotes clotting within seconds.

An Oct. 26, 2015 Rice University news release, which originated the news item, provides more details (Note: Links have been removed),

Rice chemist Jeffrey Hartgerink, lead author Vivek Kumar and their colleagues reported their discovery in the American Chemical Society journal ACS Biomaterials Science and Engineering. The hydrogel may be most useful for surgeries, particularly for patients who take anti-coagulant drugs to thin their blood.

“It’s interesting that you can take something so deadly and turn it into something that has the potential to save lives,” Hartgerink said.

Batroxobin was recognized for its properties as a coagulant – a substance that encourages blood to clot – in 1936. It has been used in various therapies as a way to remove excess fibrin proteins from the blood to treat thrombosis and as a topical hemostat. It has also been used as a diagnostic tool to determine blood-clotting time in the presence of heparin, an anti-coagulant drug.

“From a clinical perspective, that’s far and away the most important issue here,” Hartgerink said. “There’s a lot of different things that can trigger blood coagulation, but when you’re on heparin, most of them don’t work, or they work slowly or poorly. That obviously causes problems if you’re bleeding.

“Heparin blocks the function of thrombin, an enzyme that begins a cascade of reactions that lead to the clotting of blood,” he said. “Batroxobin is also an enzyme with similar function to thrombin, but its function is not blocked by heparin. This is important because surgical bleeding in patients taking heparin can be a serious problem. The use of batroxobin allows us to get around this problem because it can immediately start the clotting process, regardless of whether heparin is there or not.”

The batroxobin combined with the Rice lab’s hydrogels isn’t taken directly from snakes, Hartgerink said. The substance used for medicine is produced by genetically modified bacteria and then purified, avoiding the risk of other contaminant toxins.

The Rice researchers combined batroxobin with their synthetic, self-assembling nanofibers, which can be loaded into a syringe and injected at the site of a wound, where they reassemble themselves into a gel.

Tests showed the new material stopped a wound from bleeding in as little as six seconds, and further prodding of the wound minutes later did not reopen it. The researchers also tested several other options: the hydrogel without batroxobin, the batroxobin without the hydrogel, a current clinical hemostat known as GelFoam and an alternative self-assembling hemostat known as Puramatrix and found that none were as effective, especially in the presence of anti-coagulants.

The new work builds upon the Rice lab’s extensive development of injectable hydrogel scaffolds that help wounds heal and grow natural tissue. The synthetic scaffolds are built from the peptide sequences to mimic natural processes.

“To be clear, we did not discover nor do any of the initial investigations of batroxobin,” Hartgerink said. “Its properties have been well-known for many decades. What we did was combine it with the hydrogel we’ve been working on for a long time.

“We think SB50 has great potential to stop surgical bleeding, particularly in difficult cases in which the patient is taking heparin or other anti-coagulants,” he said. “SB50 takes the powerful clotting ability of this snake venom and makes it far more effective by delivering it in an easily localized hydrogel that prevents possible unwanted systemic effects from using batroxobin alone.”

SB50 will require FDA approval before clinical use, Hartgerink said. While batroxobin is already approved, the Rice lab’s hydrogel has not yet won approval, a process he expects will take several more years of testing.

Here’s a link to and a citation for the paper,

Nanofibrous Snake Venom Hemostat by Vivek A. Kumar, Navindee C. Wickremasinghe, Siyu Shi, and Jeffrey D. Hartgerink. ACS Biomater. Sci. Eng., Article ASAP
DOI: 10.1021/acsbiomaterials.5b00356 Publication Date (Web): October 22, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Sponging up the toxins in your blood

It doesn’t sound like these nanosponges are going to help you with your hangover but should you have a snakebite, an E. coli infection or other such pore-forming toxin in your blood, engineers at the University of California at San Diego are working on a solution. From the University of California at San Diego Apr. 14, 2103 news release,

Engineers at the University of California, San Diego have invented a “nanosponge” capable of safely removing a broad class of dangerous toxins from the bloodstream – including toxins produced by MRSA, E. coli, poisonous snakes and bees. These nanosponges, which thus far have been studied in mice, can neutralize “pore-forming toxins,” which destroy cells by poking holes in their cell membranes. Unlike other anti-toxin platforms that need to be custom synthesized for individual toxin type, the nanosponges can absorb different pore-forming toxins regardless of their molecular structures. In a study against alpha-haemolysin toxin from MRSA, pre-innoculation with nanosponges enabled 89 percent of mice to survive lethal doses. Administering nanosponges after the lethal dose led to 44 percent survival.

They’ve produced a video about their work,

I like the fact that this therapy isn’t specific but can be used for different toxins (from the news release),

“This is a new way to remove toxins from the bloodstream,” said Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering and the senior author on the study. “Instead of creating specific treatments for individual toxins, we are developing a platform that can neutralize toxins caused by a wide range of pathogens, including MRSA and other antibiotic resistant bacteria,” said Zhang. The work could also lead to non-species-specific therapies for venomous snake bites and bee stings, which would make it more likely that health care providers or at-risk individuals will have life-saving treatments available when they need them most.

Here’s how the nanosponges work (from the news release),

In order to evade the immune system and remain in circulation in the bloodstream, the nanosponges are wrapped in red blood cell membranes. This red blood cell cloaking technology was developed in Liangfang Zhang’s lab at UC San Diego. The researchers previously demonstrated that nanoparticles disguised as red blood cells could be used to deliver cancer-fighting drugs directly to a tumor. …

Red blood cells are one of the primary targets of pore-forming toxins. When a group of toxins all puncture the same cell, forming a pore, uncontrolled ions rush in and the cell dies.

The nanosponges look like red blood cells, and therefore serve as red blood cell decoys that collect the toxins. The nanosponges absorb damaging toxins and divert them away from their cellular targets. The nanosponges had a half-life of 40 hours in the researchers’ experiments in mice. Eventually the liver safely metabolized both the nanosponges and the sequestered toxins, with the liver incurring no discernible damage. [emphasis mine]

It’s reassuring to see that this therapy doesn’t damage as it heals.

For those interested, here’s some technical information about how the nanosponges are created in the laboratory (from the news release),

Each nanosponge has a diameter of approximately 85 nanometers and is made of a biocompatible polymer core wrapped in segments of red blood cells membranes.

Zhang’s team separates the red blood cells from a small sample of blood using a centrifuge and then puts the cells into a solution that causes them to swell and burst, releasing hemoglobin and leaving RBC [red blood cell] skins behind. The skins are then mixed with the ball-shaped nanoparticles until they are coated with a red blood cell membrane.

Just one red blood cell membrane can make thousands of nanosponges, which are 3,000 times smaller than a red blood cell. With a single dose, this army of nanosponges floods the bloodstream, outnumbering red blood cells and intercepting toxins. Based on test-tube experiments, the number of toxins each nanosponge could absorb depended on the toxin. For example, approximately 85 alpha-haemolysin toxin produced by MRSA, 30 stretpolysin-O toxins and 850 melittin monomoers, which are part of bee venom.

In mice, administering nanosponges and alpha-haemolysin toxin simultaneously at a toxin-to-nanosponge ratio of 70:1 neutralized the toxins and caused no discernible damage.

This seems like promising work and, hopefully, they will be testing these nanosponges in human clinical trials soon.

Here’s a link to and a citation for the researchers’ paper,

A biomimetic nanosponge that absorbs pore-forming toxins by Che-Ming J. Hu, Ronnie H. Fang, Jonathan Copp, Brian T. Luk,& Liangfang Zhang. Nature Nanotechnology (2013) doi:10.1038/nnano.2013.54 Published online 14 April 2013

This paper is behind a paywall. (H/T to EurekAlert [Apr. 14, 2013 news release].)

The last time I wrote about nanosponges it was in the context of oil spills in my Apr. 17, 2012 posting.