Mississippi researchers use FRESH 3D printing to deliver chemotherapy drugs directly to tumor sites

Researchers at the University of Mississippi School of Pharmacy have demonstrated that 3D printed hydrogel implants loaded with drug-filled nanocarriers could concentrate chemotherapy at a tumor site rather than dispersing it throughout the body. The team claims the method could reduce severe side effects associated with traditional cancer treatment.

The study, published in Pharmaceutical Research, used spanlastics — highly deformable nanovesicles composed of Sorbitan Monostearate (Span 60) and an edge activator, Polyethylene sorbitol ester (Tween 80) — to encapsulate doxorubicin, a commonly used chemotherapy drug.

Those vesicles were then embedded in sodium alginate hydrogels and fabricated into disc-shaped implants using Freeform Reversible Embedding of Suspended Hydrogels (FRESH) bioprinting.

“Delivering chemotherapeutics is always a nasty business because of the severe side effects that the patients experience,” explained Jaidev Chakka, Principal Scientist in the School of Pharmacy at the University of Mississippi. “The goal of this publication is: ‘How we can minimize those side effects?’”

From nanoparticle to nucleus

Each spanlastic vesicle measured between 200 and 300 nanometers — a fraction of the width of a human hair — allowing the carriers to pass through cell membranes and deposit doxorubicin directly inside cancer cells. Encapsulation efficiency ranged from 33% to 45%, and particle size remained stable over eleven days.

“Every drug for cancer has to act inside the cell, either on RNA or on DNA or inhibiting a cell pathway,” Chakka said. “If the drug is not able to penetrate the cell membrane or be taken up by the cell, the effect of the drug is none. But when we put that drug in a nanoparticle, we are also protecting the drug from degradation, so we are actually pushing a good amount of drug molecules into the cell in one go.”

“Having the drug in an implant, or in our case, a 3D printed construct, and placing that construct at the tumor sites means we can concentrate the delivery to the tumor area, instead of throughout the whole body,” said Elom Doe, a third-year doctoral student in pharmaceutical sciences at the university.

In vivo testing is still required

The work does still remain at the laboratory stage, however. “What we did is test how the drug acts in vitro or outside the body,” Doe said. “We would have to test it in in-vivo models before we can think of delivering it to patients, and that’s not a job you can do in a day.”

“With this study, we did two things: One is using 3D printing as a fabricating method for a hydrogel-based drug delivery system,” Chakka added. “The second one is that we demonstrated these drug delivery systems can be effective in killing cancer cells in vitro, but there is still a long way to go.”