A Fullerene−Paclitaxel Chemotherapeutic:  Synthesis, Characterization, and Study of Biological Activity in Tissue Culture

• Published in: Journal of the American Chemical Society 2005-09, Vol.127 (36), p.12508-12509
• Main Authors: Zakharian, Tatiana Y, Seryshev, Alexander, Sitharaman, Balaji, Gilbert, Brian E, Knight, Vernon, Wilson, Lon J
• Format: Article
• Language: English
• Subjects: Aerosols - administration & dosage; Aerosols - metabolism; Antineoplastic agents; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Drug Delivery Systems; Drug Screening Assays, Antitumor; Fullerenes - chemistry; Fullerenes - pharmacokinetics; General pharmacology; Humans; Liposomes; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Medical sciences; Molecular Structure; Paclitaxel - chemical synthesis; Paclitaxel - chemistry; Paclitaxel - pharmacokinetics; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Tissue Culture Techniques
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0546525

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.