Journal
NATURE CHEMISTRY
Volume 4, Issue 6, Pages 503-510Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.1326
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Funding
- Maryland Department of Business and Economic Development (Nano-Bio Initiative)
- Maryland Technology Development Corporation
- National Science Foundation [CHE-1110911]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1110911] Funding Source: National Science Foundation
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The solubility characteristics of 40-70% of new drug candidates are so poor that they cannot be formulated on their own, so new methods for increasing drug solubility are highly prized. Here, we describe a new class of general-purpose solubilizing agents-acyclic cucurbituril-type containers-which increase the solubility of ten insoluble drugs by a factor of between 23 and 2,750 by forming container-drug complexes. The containers exhibit low in vitro toxicity in human liver, kidney and monocyte cell lines, and outbred Swiss Webster mice tolerate high doses of the container without sickness or weight loss. Paclitaxel solubilized by the acyclic cucurbituril-type containers kills cervical and ovarian cancer cells more efficiently than paclitaxel alone. The acyclic cucurbituril-type containers preferentially bind cationic and aromatic drugs, but also solubilize neutral drugs such as paclitaxel, and represent an attractive extension of cyclodextrin-based technology for drug solubilization and delivery.
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