Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 99, Issue 8, Pages 3542-3551Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.22112
Keywords
target; nanocrystal, high drug loading; cancer therapy
Funding
- University of North Carolina at Chapel Hill
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A novel nanocrystal formulation of hydrophobic drugs has been developed for cancer therapy The new method, called a three-phase nanoparticle engineering technology (3PNET), includes three phases: phase 1, amorphous precipitate; phase 2, hydrated amorphous aggregate; and phase 3, stabilized nanocrystal The 3PNET has been applied to two anticancer drugs, paclitaxel (PTX) and camptothecin (CPT), using Pluronic F127 (F127) polymer as a single excipient. The nanocrystals encapsulated over 99% of the drug with a high ratio of drug to excipient The nanocrystal formulation of PTX did not induce hemolysis at pharmacologically relevant concentrations. Antitumor activity in two tumor models, human lung cancer and murine breast cancer, demonstrated that intravenously injected nanocrystals significantly inhibited the tumor growth. The nanocrystals also showed significant therapeutic effects via oral administration In addition, the nanocrystals could be further modified for targeted delivery of PTX by conjugating a folate ligand to F127. The new nanomedicine formulations show clear potential for clinical development because of the excellent antitumor activity, low toxicity, and the ease of scale-up manufacture The formulation method may apply to other hydrophobic drugs (C) 2010 Wiley-Liss, Inc and the American Pharmacists Association J Pharm Sci 99 3542-3551,2010
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