Established drug delivery companies, start-ups, and academia are advancing nanotechnology in oral, injectable, transdermal,
and implantable systems as a means to improve bioavailability for a variety of drugs.
Nanotechnology at work
Start-up companies as well as established companies are pursuing commercial development of nanotechnology-based delivery systems
(see Table I). Elan Corporation's "NanoCrystal" technology, for example, is designed to improve the delivery of poorly water-soluble drugs by transforming
them into nanometer-sized particles, typically less than 1000 nm in diameter, which are produced by milling the drug substance
using a proprietary wet-milling technique, according to company information. The NanoCrystal particles of the drug are stabilized
against agglomeration by surface adsorption of select stabilizers. The result is an aqueous dispersion of the drug substance
that behaves like a solution, a "NanoCrystal Colloidal Dispersion," which can be processed into finished-dosage forms.
Table I: Select companies involved in nanotechnology-based drug delivery.
Elan has four products, approved in the United States, which use the NanoCrystal technology: Wyeth's (Madison, NJ) "Rapamune" (sirolimus), Merck & Co.'s (Whitehouse Station, NJ), "Emend" (aprepitant), Abbott Laboratories' (Abbott Park, IL) "Tricor" (fenofibrate), and Par Pharmaceutical's (Woodcliff Lake, NJ) "Megace ES" (megestrol). Elan also has a pact with Abbott and AstraZeneca to use the NanoCrystal technology
in developing a combination product of fenofibrate and AstraZeneca's (London) "Crestor" (rosuvastatin). Elan is partnered
with Johnson & Johnson (J&J, New Brunswick, NJ) for the NanoCrystal technology in J&J's long-acting injectable form of paliperidone that is under
Baxter Healthcare's "Nanoedge" dispersion technology is another example of a commercial nano-based approach. The particle size is reduced to
a nanometer size range to increase the surface area, thereby increasing the rate of dissolution by using two complementary
processes, homogenization and precipitation.
pSivida (Perth, Australia), which recently signed a $165-million pact with Pfizer for ophthalmic delivery, owns the right to develop
and commercialize "BioSilicon," a nanostructured porous silicon for drug delivery. BioSilicon is composed of elemental silicon
that is processed to create a honeycomb structure of pores. These pores can be formed into various shapes and sizes and filled
with drugs, including small chemical entities, peptides, and proteins, according to the company. pSivida is targeting the
technology for formulating poorly water-soluble drugs and for controlled, slow-release drug delivery.
pSivida's lead product using BioSilicon is "BrachySil," a brachytherapy treatment in Phase II trials, which involves the
localized delivery of radioactive agents directly into a tumor. The product is licensed to Beijing Med-Pharm Corp. (Plymouth Meeting, PA).
Insert Therapeutics (Pasadena, CA), a subsidiary of the nanotechnology company Arrowhead Research Corporation (Pasadena, CA), is using a nano-engineered polymeric drug delivery system,"Cyclosert," to deliver small molecules and nucleic
acids. The system is based on linear cyclodextrin-containing polymers. Insert Therapeutics is licensing the technology to
R&D Biopharmaceuticals GmbH (Planegg, Germany) to deliver the anticancer agent tubulysin A. R&D Biopharmaceuticals recently signed a pact with Insert
Therapeutics to use the technology in developing epothilones, microtubule depolymerization inhibitors used as anticancer therapies.