Nanotechnology Advances in Drug Delivery - Pharmaceutical Technology

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Nanotechnology Advances in Drug Delivery
Nanotechnology is emerging as a tool for resolving challenge in delivering poorly water soluble and highly potent drugs.

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Insert Therapeutics is further licensing the technology to another Arrowhead subsidiary, Calando Pharmaceuticals (Pasadena, CA), which develops small interfering RNA (siRNA) therapeutics. Calando's lead drug candidate, CALAA-01, is a nanoparticle containing nonchemically modified siRNA and a transferrin protein-targeting agent formulated with Calando's "Rondel" (RNA/Oligonucleotide Nanoparticle Delivery) technology.

Academia pursues nanotechnology

Researchers at Princeton University (Princeton, NJ) recently developed a new technique, "Flash NanoPrecipitation," which allows for mixing drugs and the materials that encapsulated them, according to a May 2007 university release. Similar mixing techniques previously have been used to create bulkier pharmaceutical products and have proven practical on a commercial scale.

The Princeton-led team, which includes chemical engineering professors Robert Prud'homme, Yannis Kevrekidis, and Athanassios Panagiotopoulos, is the first to apply the technology to create nanoparticles that are 100–300 nm wide, according to the release. Particles in this size range also could improve the delivery of inhaled drugs because they are large enough to remain in the lungs, but too small to trigger the body's lung-clearing defense systems. This trait could maximize the effectiveness of inhaled, needle-free vaccination systems.

In NanoPrecipitation, two streams of liquid are directed toward one another in a confined area. The first stream consists of an organic solvent that contains the drug and polymer, and the second stream contains pure water, outlines the release. When the streams collide, the hydrophobic drug and polymers precipitate out of solution, and the polymers immediately self-assemble onto the drug cluster to form a coating with the hydrophobic portion attached to the nanoparticle core and the hydrophilic portion stretching out into the water. By carefully adjusting the concentrations of the substances and the mixing speed, the sizes of the nanoparticles can be controlled. The stretched hydrophilic polymer layer keeps the particles from clumping together and prevents recognition by the immune system so that the particles can circulate through the bloodstream.

Researchers at the University of Pennsylvania School of Medicine & School of Engineering and Applied Science (Philadelphia, PA) used a cylindrical carrier to sustain delivery of the anticancer drug paclitaxel to an animal model of lung cancer 10 times longer than that delivered on spherical-shaped carriers, according to an April 2007 university release. The research team used skinny cylindrical nanoparticles composed of synthetic polymers to deliver the anticancer drug paclitaxel to human lung tumor tissue implanted in mice. The cylinders have diameters as small as 20 nm and lengths approaching the size of blood cells. The paclitaxel shrunk the tumors, and because the cylinders remained in circulation for up to one week after injection, they delivered a more effective dose, killing more cancer cells and shrinking the tumors to a much greater extent, an improvement over spherical nanoparticles (1).

Magnetic nanocrystalline iron-nickel alloys is another nano-based advance in drug delivery. Researchers at the University of Louisiana at Lafayette (Lafayette, LA) prepared magnetic nickel ferrite nanocrystals coated with the biocompatible polymer polymethacrylic acid (PMAA) and developed methods of hooking the anticancer agent doxorubicin to the ends of the PMAA chains (2).


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