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Paclitaxel is a powerful anticancer agent used to treat a variety of malignancies, but severe side effects limit its ultimate effectiveness and utility. To improve this drug's pharmacological properties, researchers have turned to nanoparticle-based delivery agents, although with marginal success; stably trapping large amounts of paclitaxel in most nanoparticles has proven difficult. Now, researchers at the University of Illinois at Urbana-Champaign have developed a new process for making nanoparticles that relies on paclitaxel itself to serve as the initiator that triggers polymer synthesis. The result is not only a stable nanoparticle formulation of paclitaxel but also one with very high and very controlled amounts of drug being incorporated in the nanoparticle.
Reporting their work in the journal Angewandte Chemie International Edition, Jianjun Cheng, Ph.D., a member of the Siteman Center of Cancer Nanotechnology Excellence (SCCNE), and graduate student Rong Tong, a student fellow funded by the SCCNE, describe the "living polymerization" technique they used to grow polymer nanoparticles that incorporate paclitaxel in the chemical structure of the polymer. The beauty of this process is that it provided the investigators with the ability to predetermine how much paclitaxel would end up in the nanoparticle merely by adjusting the ratio of drug molecule to lactide, the monomer from which polylactide is made. The investigators coat the final nanoparticle with a layer of poly(ethylene glycol) (PEG) to increase circulation time in the body.
Also important is the fact that the chemical linkage that binds paclitaxel to the polymer backbone can be broken down slowly in the body, providing sustained release of the drug once it reaches a tumor. Most nanoparticulate formulations of paclitaxel have been plagued by what researchers call "burst release," which delivers as much as 90% of the drug within a few hours.
The researchers also note that this technique should be applicable for entrapping any drug that, like paclitaxel, contains hydroxyl groups in its chemical structure. In fact, they report that they have prepared stable nanoparticles containing the anticancer drugs docetaxel and camptothecin using their living polymerization technique.
About National Cancer Institute
To help meet the goal of reducing the burden of cancer, the National Cancer Institute (NCI), part of the National Institutes of Health, is engaged in efforts to harness the power of nanotechnology to radically change the way we diagnose, treat and prevent cancer.
The NCI Alliance for Nanotechnology in Cancer is a comprehensive, systematized initiative encompassing the public and private sectors, designed to accelerate the application of the best capabilities of nanotechnology to cancer.
Currently, scientists are limited in their ability to turn promising molecular discoveries into benefits for cancer patients. Nanotechnology can provide the technical power and tools that will enable those developing new diagnostics, therapeutics, and preventives to keep pace with today’s explosion in knowledge.
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