A fullerene-paclitaxel chemotherapeutic: synthesis, characterization, and study of biological activity in tissue culture.

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.

• Authors: Tatiana Y Zakharian, Alexander Seryshev, Balaji Sitharaman, Brian E Gilbert, Vernon Knight, Lon J Wilson
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 127 Issue 36 Pg. 12508-9 (Sep 14 2005) ISSN: 0002-7863 [Print] United States
• PMID: 16144396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aerosols
• Fullerenes
• Liposomes
• Paclitaxel

Topics

• Aerosols (administration & dosage, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Delivery Systems
• Drug Screening Assays, Antitumor
• Fullerenes (chemistry, pharmacokinetics)
• Humans
• Liposomes
• Lung Neoplasms (drug therapy, metabolism)
• Molecular Structure
• Paclitaxel (chemical synthesis, chemistry, pharmacokinetics)
• Tissue Culture Techniques