Multifunctional Poly(amidoamine) Dendrimer-Taxol Conjugates: Synthesis, Characterization and Stability
A series of multifunctional dendrimer-taxol conjugates have been synthesized for targeted drug delivery, based on the selected amine-terminated poly(amidoamine) dendrimer of generation 5 (PAMAM G5) as a platform. An imaging agent (fluorescein isothiocyanate), a targeting agent (folic acid), and taxol were sequentially covalently conjugated to the dendrimer. Two linkers, succinic acid and glutaric acid, were employed to attach taxol to dendrimer. The synthesized multifunctional dendrimer conjugates were extensively characterized using a variety of techniques including nuclear magnetic resonance (NMR), UV-Vis spectrometry, reverse-phase high performance liquid chromatography (RP-HPLC), and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF mass spectrometry). Stability assays indicated that the two dendrimer-taxol conjugates exhibited different rates of taxol release. A kinetic study of the hydrolysis of the succinic acid linker/dendrimer conjugate using quantitative thin layer chromatography (TLC) showed that the conjugate released free taxol over time through hydrolysis in PBS buffer with a half-life of 10 hours, while no significant taxol release was observed for the glutaric acid linker/dendrimer conjugate after 7 days in the same conditions. The synthesized PAMAM dendrimer-based multifunctional dendrimer-taxol conjugates are ready for experiments in targeted cancer therapy.
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Document Type: Research Article
Publication date: 2007-09-01
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