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A fullerene-paclitaxel chemotherapeutic: synthesis, characterization, and study of biological activity in tissue
Tatiana Y Zakharian1, Alexander Seryshev, Balaji Sitharaman
1Department of Chemistry and the Center of Nanoscale Science and Technology, Rice University, P.O. Box 1892, Houston, Texas 77251-1892, USA.
Abstract:
A fullerene-paclitaxel conjugate has been synthesized as a slow-release drug for aerosol liposome delivery of paclitaxel for lung cancer therapy. The conjugate was designed to release paclitaxel via enzymatic hydrolysis and subsequently has shown a half-life of release of 80 min in bovine plasma. A liposome formulation of the conjugate has been prepared using dilauroylphosphatidylcholine (DLPC), and its IC50 is virtually identical to the IC50 for a paclitaxel-DLPC formulation in human epithelial lung carcinoma A549 cells. With both clinically relevant kinetics of hydrolysis and significant cytotoxicity in tissue culture, the conjugate holds promise for enhanced therapeutic efficacy of paclitaxel in vivo.
