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Kevin SillCancer patients may have more hope of survival thanks to the IVECT Method.

For people living with cancer, treating their disease successfully is often marred by the many side effects associated with intravenous chemotherapy. Emerging drug delivery technologies focus on limiting the exposure of healthy cells to these toxic agents, but few have the potential to improve patient care in a significant way. Kevin N. Sill, PhD, R&D Magazine’s first ever Young Innovator of the Year and chief scientific officer of Intezyne Technologies, Inc. (Tampa, Fla.), has designed an advanced method for encapsulating a wide variety of therapeutic agents into a polymer-based drug delivery system, called the IVECT Method.

Sill’s journey to co-founding Intezyne, and developing the IVECT Method and cross-linking technology behind it, started during his graduate work at the Univ. of Massachusetts, Amherst. “My colleague, Habib Skaff, had said he was going to start a company and wanted me to come along with him. I was more than happy to do so,” says Sill. After taking this opportunity, Sill and his colleague began to discuss how they could use their unique skills in polymer chemistry to make an impact and better people’s lives. After looking at literature, and current unmet needs, the men decided to focus on nano-scale drug delivery devices, specifically polymer micelles.

Although the theory behind using synthetic polymers for drug delivery devices had been around since the 1970s, there were still issues that needed to be resolved, “such as the stability of the polymer micelle after administration, and the ability to target specific tissue using those micelles,” explains Sill. Other researchers “tried to piece together polymers off the shelf and use commercially available components in order to circumvent a lot of the problems that were coming up in drug delivery,” states Sill. However, none found the “magic bullet” they all hoped for: a stable drug delivery system.

Traditional polymer micelles utilize a diblock copolymer. “You have a block that hates water, and a block that loves water. When placed in water, the copolymers self-assemble, with the highest water-hating segment making up the core and the water-loving part on the outside,” says Sill. With this core-shell delivery device, scientists can encapsulate a high performance drug, such as current chemotherapy drugs, into the core.

The problem behind other micelle drug delivery devices is that upon administration of the body, the device comes in contact with the blood proteins and phospholipids, causing the micelle to fall apart. Once the micelle releases the drug into the bloodstream, you lose all benefit of these carriers and healthy tissues are exposed to toxic drugs.

These issues, and others, were solved within the first four years after founding Intezyne, with the development of Sill’s advanced micelle drug delivery technology, the IVECT Method. The method is versatile enough to encapsulate a wide range of therapeutics, including small molecules, magnetic contrast agents, and genetic materials (sRNA and DNA), while providing stability and protection against systemic drug exposure.

Cross-linked to innovation
Sill explained his idea behind the IVECT stabilization technology, a reversible cross-linker, came from a paper he was reading on polymer chemistry that had been out since the 1930s. “It defined a reaction that had all the attributes we were looking for at Intezyne,” says Sill. It was very facile, highly pH sensitive, and the cross-linking reversed almost instantaneously. “We ran a couple pilot studies, based upon these findings, and the chemistry looked perfect for this application,” continues Sill.

By adding a cross-linkable stabilizer region, Sill took the idea of a diblock copolymer a step further in the realms of drug delivery by creating structural elements of a triblock copolymer. Furthermore, Sill is able to take advantage of both active and passive targeting technologies, by adding tumor-specific targeting groups to the outer shell of the micelle. While the stabilizer block allows the micelle to accumulate passively within diseased tissues, the use of targeting ligands to hone in on the area and localize takes advantage of active cell targeting.

This triblock copolymer, the key structure behind the IVECT Method, allows the patient to get a high amount of the drug, without the toxic chemicals hitting the rest of the body. What is important about Sill’s technology is that the drug is trapped. Sill explains, “The cross-linking technology is physically connecting the polymer chains together in order to keep them bound while the micelle circulates.” It is only within diseased tissues that the chemistry of the cross-linker is undone and the drug is released.

Science, IP, and INDs
As chief science officer at Intezyne, not only is Sill the primary designer of the IVECT system and the innovator of the cross-linking technology, but he oversees a team of PhD-level scientists and conducts everyday research. He is heavily involved with securing the Company’s intellectual property, and has filed many patents for the company, several of which have been issued in the United States, Europe, and Japan. Currently, Sill is responsible for the development of four new drug products that utilize his IVECT Method. He and his team are working on IT-141, encapsulated SN-38 for metastatic colorectal cancer, which is positioned for a Q2 2010 Investigational New Drug (IND) filing; IT-143, encapsulated doxorubicin for anaplastic thyroid cancer, with a target IND submission in Q4 2010; IT-145 for pancreatic cancer, currently in pre-clinical development; and IT-121 a gene therapy based on oncology product, also in pre-clinical development.

Despite the potential of the IVECT Method, Sill states, “there is certainly a lot of work that still has to be done.” In the future, Sill believes his method could make a difference in Alzheimer's Disease and gene therapy as well. “We have not found a limit to the types of materials we are able to encapsulate with the IVECT Method. There are a lot of areas that we could start to explore,” says Sill.

It is this that excites Intezyne and Sill, along with the idea of the possibility of entering the world of personalized medicine, which will push the limits of this technology. Currently, Intezyne plans to remain focused on its primary goals and bring its lead product to clinical stage drug development.

“We are moving forward in the field of oncology,” says Sill.

Published in R & D magazine: Vol. 51, No. 7, December, 2009, pp.8-9.

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