April 2007 - Pharmaceutical Technology

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PharmTech Europe

April 2007

Pharmaceutical Technology

Synthesizing pharmaceutical intermediates

Manufacturers routinely look for stategies to improve production efficiency. One option is to increase yield. Jack Rosazza, professor emeritus of the University of Iowa, says a research team is pursuing reactions that might produce pharmaceutical intermediates on a large scale. Researchers are using complex enzymes called dioxygenases to produce chiral intermediates such as alpha naphthol with pharmaceutical applications. "What we develop with alpha naphthol," Rosazza says, "should be applicable to almost any aromatic material that could serve as a potential feedstock for making pharmaceutical intermediates." Improved chemical reactions could save time and costs by increasing the efficiency of synthesis.

Oxidations can be used to produce pharmaceutical intermediates. These reactions generally are avoided, however, because they generate pollution and require dangerous reagents such as explosive peroxyacids. Professor Horacio Olivo of the University of Iowa is conducting research that gives manufacturers a safe way to perform oxidations. Olivo uses lipases to generate peroxyacids in situ, so chemists do not have to handle them. The lipases then can be recycled and reused. In addition, Olivo uses ethyl acetate as a solvent for oxidations. Ethyl acetate is environmentally benign and does not require cleanup or special handling like chlorinated solvents do. Olivo's techniques greatly improve safety, reduce pollution, and involve reusable materials. All of these advantages may translate into significant cost savings for manufacturers.
-Erik Greb


Nanotubes Show Drug-Delivery Potential

London (Feb. 1)—Researchers at the University of London's ( http://www.lon.ac.uk/) School of Pharmacy have chemically modified carbon nanotubes to enable them to enter human cancer cells. Crossing biological barriers is the key step to using nanotubes as drug-delivery mechanisms.

The nanotubes were modified by various functional groups and incubated with live cells, including mammalian, bacterial, and fungal cells. The study showed that the various types of nanotubes showed "a capacity for cellular uptake and cross-intracellular movement without causing cell death," according to a university press release.

Kostas Kostraelos, deputy head of the Centre for Drug Delivery Research, led the research team. He explains that the nanotubes moved through the cells either as individual nanotubes or as small bundles, acting as "nanoneedles" into the plasma membrane without damaging or killing the cell.

The team plans to study the behavior of the nanotubes with various cell types and conduct toxicity studies.
-Maribel Rios


Novel Polymer–DNA Delivery System

Enschede, Netherlands (Feb. 26)—Scientists from the University of Twente's MESA+ Institute for Nanotechnology ( http://www.utwente.nl/en/) have designed a novel delivery system by combining synthetic iron-containing polymers with DNA macromolecules.

When the polymer is wrapped around the DNA, they are bonded electrostatically, and the process generates spherical, porous structures capable of carrying and delivering drugs and DNA fragments. The pores are larger than 50 nm.

Company Notes
Local delivery is possible using small molecules to oxidize the iron and break the bond between the DNA and polymer. This process also can be used to free DNA fragments from the sphere and apply them in gene therapy.

The research team, led by professors Julius Vancso (MESA+ Institute for Nano-technology) and Helmuth Mohwald (Max Planck Institut fFCr Kolloid und GrenzflE4chenforschung, Golm, Germany, http://www.mpikg-golm.mpg.de/), published their study in the Feb. 26 issue of Angewandte Chemie International Edition.
-Maribel Rios


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