MTCTM
Abstract
Paclitaxel is a promising antitumor agent for head and neck cancer. An alloy of iron and activated carbon was formulated in the size range of 0.5–2 µm as a novel magnetically targetable carrier (MTCTM) for this drug. Quantitative UV and HPLC assays were used to measure the extent of binding and release of paclitaxel to and from activated carbons and their iron alloys. Drug binding was dependent on type and source of activated carbon. Iron alone did not adsorb paclitaxel. A type E carbon and iron alloy at 30:70 ratio was selected as prototype MTCTM Other iron/carbon ratios did not significantly improve adsorption. Binding was not affected by temperature or incubation time. Paclitaxel was chemically stable by HPLC assay during adsorption on and sustained desorption from MTCTM. The adsorption kinetics of paclitaxel to Type E carbon and to MTCTM behaved according to Langmuir’s isotherm. It was found in sera that 38% of adsorbed drug could be released from the paclitaxel-MTCTM over 24 hours. In addition the MTCTM could be localized (retained) quantitatively in a magnetic field at capillary (0.2 cm/sec) to arteriole (28 cm/sec) flow rates. The flow media was either water or in order to simulate blood viscosity, aqueous glycerol (AG). The cytotoxicity of paclitaxel derived from a specific MTCTM was identical to the same amount of free drug using a human tumor cell line of the oropharynx. The cytotoxicity of paclitaxel in vitro was not affected by the presence or absence of magnetic field retention of a specific MTCTM over the tumor cells. In conclusion, we have successfully prepared a prototype MTCTM specific for paclitaxel that can release clinically relevant amounts of drug for greater than 24 hours. and can be localized in a magnetic field at arteriole flow rates.
Keywords
Activate Carbon Tumor Blood Flow Intraarterial Chemotherapy Albumin Microsphere Activate Carbon ParticlePreview
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References
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