In the ongoing battle against cancer, a Massachusetts startup is taking a novel approach to drug delivery that could significantly improve treatment outcomes while reducing the harsh side effects that often accompany chemotherapy. Enzian Pharmaceutics, founded by MIT alumni, has developed a new type of oral tablet that delivers cancer drugs more evenly over time, potentially transforming how patients receive treatment.
The Innovation: 3D-Printed Fibrous Tablets
Unlike traditional oral cancer medications that quickly dissolve in the stomach and deliver a sudden burst of chemicals into the bloodstream, Enzian’s tablets are designed for controlled release. The company’s proprietary technology uses tiny 3D-printed fibers that transform into a gel-like substance when exposed to water.
“A lot of orally delivered cancer drugs could benefit from this,” says Aron Blaesi PhD ’14, who founded the company in 2016. “Right now, soon after someone has taken a cancer drug, its concentration in the blood can be up to 50 times greater than when they are supposed to take the next pill.”
This dramatic fluctuation in drug concentration is responsible for many of the severe side effects associated with traditional chemotherapy, as the sudden influx of chemicals affects not just cancer cells but also healthy tissues in the heart, liver, and brain. By contrast, Enzian’s technology aims to maintain a steadier concentration of the drug in the body, potentially improving both effectiveness and patient quality of life.
From MIT Research to Startup Reality
The innovation originated from Blaesi’s doctoral work at MIT’s Department of Mechanical Engineering. Early in his research, conducted as part of the Novartis-MIT Center for Continuous Manufacturing, Blaesi worked on manufacturing pills with an injection molding machine. He noticed that injection molded pills were far less porous than traditional compressed tablets.
“If you put a typical pill into a fluid or into the stomach, the fluid percolates the pores and quickly dissolves it,” Blaesi explains. “That’s not the case when you have an injection molded product.”
This observation, combined with guidance from his advisor Nannaji Saka ScD ’74, led the researchers to explore how different tablet microstructures changed the rate at which drugs are released. They moved from injection molding to 3D printing for more precision, eventually developing tightly wound microstructures that could carry drugs effectively.
Technical Breakthrough: Expandable Fibers
The breakthrough came when Blaesi experimented with different carrier materials and discovered that higher molecular weight materials took longer to dissolve because they would absorb water and expand before degrading.
“Initially I thought, ‘Oh no, the drug isn’t being dissolved fast enough anymore,’” Blaesi recalls. “Then we thought, ‘Everything has its place.’ This could stay in the stomach for longer because of the expansion. Then it could release the drug over time.”
The final tablet design features fibers arranged in a grid pattern. When water flows into the spaces between the fibers, they expand to form a strong gel-like substance that slowly erodes in the stomach while steadily releasing the drug. In animal studies, the tablets remained in the stomach for 12 to 24 hours before being safely excreted.
Addressing Cancer Drug Solubility Challenges
Many cancer drugs are only soluble in acidic solutions, meaning they can only be absorbed while in the stomach. However, on an empty stomach, traditional drugs may only remain in the stomach for 30-40 minutes, and even with a full stomach, the window is just a few hours. This limitation forces patients to take high doses immediately, creating the problematic peak concentrations that cause side effects.
- Traditional oral cancer drugs create peak concentrations up to 50 times higher than trough levels
- Short gastric residence time limits drug absorption
- High peak concentrations affect healthy organs, causing severe side effects
- Drug concentration drops too low between doses, potentially reducing effectiveness
Enzian’s technology directly addresses these challenges by extending gastric residence time and providing controlled release. For prostate cancer drugs currently dosed at several hundred milligrams per day, Blaesi hopes to reduce the dosage to about a tenth of that while achieving better therapeutic effects.
Clinical Path Forward
The company is currently validating its tablets’ ability to stay in place in a small number of healthy human volunteers. In about a year, Enzian plans to begin testing the technology’s ability to improve the effectiveness and safety of cancer drugs in patients.
This approach could have broad applications beyond prostate cancer. The company believes its technology could improve treatments for blood, skin, and breast cancers as well. The controlled release mechanism is particularly valuable in clinical trials, where demonstrating a new drug’s superiority over existing treatments is crucial, and adverse events can end a drug’s development.
Broader Implications for Drug Delivery
Controlled-release drug delivery systems represent a significant advancement in pharmaceutical science. According to research published in various medical journals, these systems offer several key benefits including reduced side effects, improved patient compliance, and more consistent therapeutic effects. The market for controlled-release drug delivery is projected to continue growing as more precise delivery mechanisms are developed (Prophecy Market Insights).
Gastroretentive drug delivery systems, like those developed by Enzian, specifically target the challenge of keeping medications in the stomach for extended periods. As noted in research from the National Center for Biotechnology Information, these systems can be particularly valuable for drugs with specific absorption windows or solubility requirements (NCBI).
Enzian’s approach to 3D printing fibrous structures represents an innovative solution to longstanding challenges in gastroretentive drug delivery. While research in this area has been ongoing for decades, the specific expandable fibrous tablet approach appears to overcome previous technical obstacles.
Looking Ahead
For cancer patients, the potential benefits of this technology are significant. By reducing the extreme fluctuations in drug concentration that characterize traditional oral chemotherapy, Enzian’s tablets could mean fewer severe side effects and more consistent treatment effectiveness.
The move into human trials represents the culmination of more than a decade of work for Blaesi, who remains confident that Enzian can deliver on its promise of improving treatments. “The opportunity is enormous,” Blaesi says. “So many oral cancer drugs have this delivery problem. We still have to do the efficacy and safety studies on patients, but we expect this to be a game changer.”
As the company moves forward with clinical trials, the medical community will be watching closely to see if this MIT-born innovation can fulfill its promise of making cancer treatment more effective and less punishing for patients.
Sources
MIT News: Startup’s tablets deliver cancer drugs more evenly over time
Prophecy Market Insights: Controlled Release Drug Delivery Market
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