It’s impossible to imagine a world without polymers. From biopolymers produced from natural sources such as protein to synthetic polymers used in medical devices, household goods, and automotive parts, we are surrounded by them, and they play essential and ubiquitous roles in everyday life.
Over the past few decades, polymeric materials have significantly impacted contemporary medicine’s evolution and have become the predominant material for the construction of medical devices. Although the FDA already approves many medical polymers for their proven biocompatibility, biostability and non-toxic biodegradation,researchers continue to push for innovative mechanical and pharmaceutical applications to advance polymeric technology for better medical care and management of many chronic diseases.
Advancing hydrogel technologies
A team of scientists from Stanford University have developed a novel polymer-nanoparticle (PNP) hydrogel that can release the popular glucagon-like peptide-1 (GLP-1) receptor agonist drugs prescribed for diabetes and weight control over a period of four months instead of the usual daily or weekly timeframe.
Polymer-based hydrogels have been widely used for drug delivery applications because of their ability to hold large amounts of water and fluids while controlling drug release based on their unique properties and biocompatibility. The team at Stanford, however, took the hydrogel a step farther by taking the mesh of polymer chains and using nanoparticles to hold the drug molecules and release them in a controlled fashion as they dissolve.
In a November 2023 study published in Cell Reports Medicine, researchers report that such a system can assist in weight management and diabetes by increasing patient drug compliance and helping those with Type 2 diabetes improve longterm health outcomes. Researchers believe that reducing the amount and timing of injections will reduce the burden on patients and ultimately increase medication compliance.
“Adherence is one of the biggest challenges in Type 2 diabetes management,” says Eric Appel, associate professor of materials science and engineering at Stanford and principal investigator on the new hydrogel that allows the slow release of diet control drugs over many months. “Ozempic works great if you take it, but compliance is the problem. The goal is to improve disease management by decreasing patient burden, and only needing three shots a year makes it much easier for people with diabetes or obesity to stick with their drug regimens.”
According to Appel, traditional gels, which are covalently crosslinked, will swell when inserted into the body, which poses a problem with long-term drug dispersal: “In our case, we’ve shown that these gels are not covalently crosslinked because of their unique assembly mechanism. Instead, it’s what we call ‘molecular velcro’ or a really strong noncovalent interaction, not unlike a strong protein-ligand, and this is what prevents the hydrogel from swelling.”
The PNP is a mesh of polymer chains and nanoparticles that hold the drug molecules and releases them as they dissolve. The hydrogels fluidlike flow can easily be injected with standard needles but with a gel-like stability that is durable enough in the body to last the entire four-month period.
The GLP-1 drug stored in the hydrogel can be injected conveniently under the skin. The “depot”, as Appel refers to it, is like a “blob” of hydrogel small enough to be comfortable and inconspicuous for the patient yet large and durable enough to last four months as the hydrogel slowly dissolves away.
“We chose four months to match the cadence that people meet with their physician or endocrinologist, which is why we were so specific with the release period,” says Appel.
“The goal is to improve disease management by decreasing patient burden – only needing three shots a year makes it much easier for people…to stick with their drug regimens.”
Eric Appel
The team tested the drug-loaded PNP hydrogel by injecting it subcutaneously into diabetic rats and found that a single shot could maintain consistent exposure to GLP-1 receptor agonists over 42 days, corresponding to their proposed once every four months therapy in humans. The rats benefitted from The GLP-1 receptor agonists, which successfully controlled their blood glucose and body weight over the four months, with comparable efficacy to daily dosing. As hydrogel drug carrier applications continue to expand and encompass other small molecule drugs, PHP hydrogel carriers could be used in other medications or for treating a more comprehensive range of diseases.
Evolving polymeric heart valve tech
Another advancing technology researchers are racing to develop is a polymer heart valve that can replace mechanical and bioprosthetic valves. Although these artificial valves have been used to replace failing valves for over 50 years, they have significant disadvantages. Mechanical valves require lifelong anticoagulation and bioprosthetic valves are prone to structural degeneration, requiring reoperation to replace the original replacement valve.
As valvular disease continues to be one of the leading causes of cardiovascular morbidity, mortality and functional disability worldwide, a solution that would overcome the limitations of current valve replacements remains top of mind for researchers, who continue to test different polymer compounds and materials for long-term durability, hemocompatibility, and other essential qualities that prove they can be the future valve replacement solution.
Dr. Joseph Kennedy, professor of polymer science and chemistry at The University of Akron, author of more than 700 original scientific publications, and inventor of over 130 issued US patents on polymer science and technology, has devised a design using a polymer material he believes is far superior to any other polymer heart valve material currently being researched or tested.
The path to a successful, fully synthetic polymer heart valve began with Kennedy’s patented Poly (Styrene-block-IsoButylene-block-Styrene) (SIBS) polymer, used as a coating for cardiac stents. However, SIBS was only the beginning of his work toward creating a polymer that could function as a heart valve.
“For SIBS, the surface was everything,” Kennedy says. Like the stent coating, the heart valve must be biocompatible, hemocompatible, calcification resistant, and possess the proper biostability properties. “The heart valve must also be rubbery, soft and durable, just like SIBS. But these key biological properties are all surface properties.”
The surface coating, however, wasn’t quite enough for the heart valve design. A polymer heart valve would have to exhibit the surface properties of SIBS while possessing the strength for structural and dynamic applications.
“After examining many possibilities, we combined the polyisobutylene polymer that is part of the SIBS structure and polyurethanes,” says Kennedy. The combination created what Kennedy calls PIB-PU (polyisobutylene-polyurethane), a new polymer with strong biocompatible rubbers suitable for heart valves and other medical devices. “Strength ensures shape retention, durability, and other properties needed in a polymer heart valve,” he says. “PIB-PU is also highly fatigue-resistant, a critical property for a beating heart whose valves constantly open and close.”
Importantly, PIB-PU is designed for the crimping necessary for transcatheter aortic valve replacement (TAVR) procedures. TAVR is quickly becoming the preferred procedure for heart valve replacement because it is minimally invasive and results in much less downtime than surgical valve replacement.
“This is a thermoplastic elastomer,” says Kennedy, “which is the same material as existing TAVR valves because they have to be squeezed together through the catheter.”
According to Kennedy, the heart valve is only one of the many possibilities for PIB-PU in medical devices: “We have started investigating other uses, including meshes and anti-adhesion barriers. There is a whole landscape of possibilities, but it started with the heart valve.”
Kennedy adds now that they have the material needed for the valve, they need animal studies to further the research.
“We have only done in vitro studies,” he says. “Rodents aren’t good for these studies. We need larger animals like sheep, dogs, or cows.”
Polymer science and medical device engineering present complex challenges. Polymers must be safe for the body and maintain their performance for an extended or designated amount of time. Despite these challenges, polymers offer pragmatic solutions that continue to redefine healthcare by providing innovative tools that can improve patients’ lives across a broad spectrum of disease and medical problems. There is no end in sight for the crucial role polymers play in medical device engineering as they pave the way for the future of healthcare.
