By Frances Bishopp

NanoSystems LLC, which has developed a technology that improves formulations of poorly water soluble products, will partner with Wyeth-Ayerst Laboratories to develop a nanoparticle formulation of (small particles of pure drug) Wyeth-Ayerst's immunosuppressant drug, Rapamune.

Under terms of the agreement, NanoSystems, of Collegeville, Pa., will apply its NanoCrystal drug formulation technology to develop a nanoparticle formulation of Rapamune for evaluation in late-stage human clinical studies.

In return, NanoSystems will receive an up-front license fee, research payments and royalties on product sales.

Specific financial details were not disclosed.

Rapamune, a macrolide antibiotic, is made by Wyeth-Ayerst, a Philadelphia-based division of American Home Products Corp.

NanoSystems' NanoCrystal technology allows the conversion of a drug ingredient to a more stable, small particle crystalline form, which has a dramatically improved bioavailability, while being physically identical to classical dosage forms.

NanoCrystals are small (less than 400 nanometers, or one billionth of a meter, in diameter) particles of crystalline drug, stabilized by absorption of selected polymers onto their surfaces.

"We take a drug substance and, through a milling process, break it down into tiny, tiny particles," Larry Sternson, president and CEO of NanoSystems, told BioWorld Today. "We then can convert those small particles into pharmaceutical dosage forms." NanoCrystals provide a unique route to formulating a wide range of structurally and therapeutically diverse molecules that, due to limited water solubility, either exhibit poor or erratic performance in clinical situations, or are refractory to traditional formulation approaches.

NanoSystems targets a significant potential market by catalyzing the clinical and commercial viability of products that would otherwise be discontinued in development due to solubility limitations. The company estimates 100,000 new chemical entities, or one-third of the compounds synthesized each year, may benefit from application of the NanoCrystal technology.

Sternson explained the company's technology can be a rescue arm for drugs that have performed poorly in the clinic and, in some instances, might have been a candidate for failure. "Poorly water-soluble drugs perform poorly in the body," Sternson said. "This technology allows us to improve the efficiency and performance of delivery."

The milling technique, Sternson explained, allows NanoSystems' methods to chop down the size of the drug crystals to very small dimensions. NanoSystems has also perfected the technique of keeping these tiny crystals stable so they don't immediately recombine to form larger particles. "When we make them small, they stay small," Sternson said.

When the particles become small, they dissolve more quickly; in oral delivery, this brings about higher bioavailability and better performance with less variability, Sternson said.

Besides oral delivery, NanoCrystal technology has been used in the development of injectable, topical and aerosol dosage forms.

The nanoparticle suspension has the look of "thin skim milk," Sternson said. However, NanoSystems has the ability to convert that suspension into solid dosage forms. "We can make capsules and tablets," Sternson said.

Additionally, NanoCrystal technology serves as a platform for targeting drugs to specific anatomical sites or for controlling delivery over time.

In 1994, NanoSystems was originally established as a business unit of Sterling Winthrop Inc., which was a subsidiary of the Eastman Kodak Co. Following the divestiture of Kodak's other health care businesses, NanoSystems, as of Dec. 21, 1995, became an independent, privately held company.

To date, eight drugs incorporating the company's technology have been tested in human clinical trials. The company has more than two dozen feasibility studies ongoing with various clients and license agreements with a number of pharmaceutical companies such as Warner-Lambert Co., of Morris Plains, N.J., Astra Draco AB, of Sodertalje, Sweden, Merck & Co., of Whitehouse Station, N.J., Mimetix Inc., of San Francisco, and Janssen Pharmaceutica N.V., a subsidiary of Johnson & Johnson. *