Few people recover completely from spinal cord injuries, and the ones that do tend to be women. This sex difference has led to interest in the use of estrogen, which has been shown to protect neurons and help them grow, as a treatment for spinal cord injury.
The challenge for this approach is finding a way to avoid side effects of high estrogen doses by delivering the hormone at low doses over an extended time period. Researchers have previously used polymeric nanoparticles to deliver the hormone. But such materials sustain delivery for only a few days or weeks.
Now, Ryan J. Gilbert, Edmund F. Palermo, and coworkers at Rensselaer Polytechnic Institute have synthesized a polymer that can release estrogen over much longer periods of time, perhaps even years. Instead of mixing estrogen with an inert carrier polymer, they incorporate it as part of the polymer (Nat. Commun. 2019, DOI: 10.1038/s41467-019-12835-w).
Their material is a copolymer of an estrogen diallyl and an ethylene glycol dithiol. The estrogen is flanked by carbonates that can release the drug via hydrolysis. The ethylene glycol dithiol acts as a modifier that chemists can use to tune the polymer’s hydrophobicity and mechanical properties.
Using photo-initiated step-growth polymerization, the researchers made the polymer large enough to be electrospun into fibers, which are desirable for providing mechanical cues for the growth of neurons in spinal cord injury. On the basis of experiments in cell cultures, the researchers predict that such fibers could be tuned to release estrogen for as long as 10 years. They are currently studying the material in mice to see if the hydrolysis rate in living systems reflects what they observed in their lab tests.
The work is “novel and highly innovative,” says Naren L. Banik, a neuroscientist at the Medical University of South Carolina who is studying estrogen as a therapy for spinal cord injuries. Testing the material on spinal cord injury in animals is necessary, he adds. “Nonetheless, prolonged and sustained delivery of estrogen using this technique has significant therapeutic potential and clinical implications.”
Kathryn Uhrich, a chemist at the University of California, Riverside, who has worked on polymerized forms of other drugs, calls the work clever and the lab results impressive. “This paper had it all—thoughtful drug design, ability to synthesize the molecule, and, most importantly, the material worked,” she says.
The RPI researchers are exploring making similar polymers with other linkers and modifiers. They’re also making hydrogels that would allow them to inject the materials. And they think the approach can be used with any drug that has two handles for attaching cleavable linkers. “We have a lot of space to play around with the material science aspect,” Palermo says.