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DRI Scientists Improve Islet Encapsulation Using Nanotechnology

Photos comparing traditional microencapsulation and nanocapsules.
Traditional microencapsulation (image left) created dead space between the protective coating and the islet. Nanocapsules (image right) conform to the cell’s outer membrane thereby eliminating this space and dramatically improving vital oxygen delivery.

Miami, FL (January 2008) -- For more than two decades, DRI scientists, biotech companies and others have been trying to develop ways to protect transplanted islets to promote their long-term survival. A potential solution sounded simple enough – encase the cells in a protective barrier that allows nutrients to flow in and insulin to flow out.

This research strategy, known as islet encapsulation technology, has been met with many challenges. Using different materials, scientists have constructed a variety of small, bubble-like casings called microcapsules in which to house the insulin-producing cells. The microcapsule would protect them from inflammatory reactions and immune attacks, while permitting the nutrients to reach the cell. However, even with improvements in these biomaterials, the very construct of a microcapsule continues to prevent islets from thriving.

While invisible to the naked eye, microcapsules are relatively large and the space within them is very big compared to the size of one islet cell. As a result, critical oxygen and other nutrients flowing in do not reach the islet in an efficient manner and adversely affect the islet cell’s health.

After observing the challenges and limitations of traditional microcapsules, the DRI’s Tissue Engineering group is developing a different encapsulation strategy using nanotechnology, the newest area of immuno-isolation research. Using the same layering technology as the microchip industry, scientists are applying microscopically-thin, “nanoscale” coatings directly to the surface of the islet cells. These coatings, made from a biocompatible polymer, serve as a physical barrier and help camouflage the islets from the recipient’s body.

The nanoencapsulation approach offers several advantages over microcapsules. In particular, the thin coatings substantially reduce the volume of the islet cells that are transplanted, which can minimize harmful side effects like clotting and high blood pressure. In addition, with nanoencapsulation, the small size of the capsules allows for transplantation into a number of areas within the body, including the liver, an alternative site or even within a transplantable device. Furthermore, nanoencapsulation could be used to protect many cell types beyond islets.

The nanoscale coatings conform to the islets like a surgical glove, eliminating the bubble-like space between the islet and the microcapsule wall. Elimination of this space speeds up oxygen delivery to the islets. The ultra-thin layers do not adversely affect the diffusion of essential nutrients to the islet’s thousands of cell components; each one should receive its share.

Taking encapsulation technology research even further, DRI scientists are now developing more “active” nanocapsules by tethering certain agents to the islet surface that will allow it to “defend” itself against an attack. For example, scientists suspect that by attaching anti-inflammatory molecules to the cells surface, they can reduce adverse reactions to transplant stress, such as clot formation and leukocyte (white blood cell) infiltration.

Integral to the success of cell protection through nanoscale technology is the development of polymers that will work in concert with the body’s cells, tissues and natural biological functions. Cherie Stabler, Ph.D., the head of the DRI’s Tissue Engineering team, and her colleagues are rigorously testing, screening and evaluating a variety of chemical compounds to develop polymers that meet these criteria.

In addition, the DRI is partnering with Dr. Jeffrey Hubbel, Director of the Integrative Biosciences Institute in Lausanne, Switzerland. World renowned for his work with biomaterials for tissue engineering and drug delivery, Dr. Hubbell is working with the DRI to develop novel polymers that can be used to make stable nanocapsules for islet cells.

Through an exhaustive, committed and disciplined research approach to finding a cure, DRI scientists continue to make progress in developing encapsulation technology and improve upon the therapies currently in use today.

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