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Synthesis and Characterization of DNA Nano-meso-microspheres as Drug Delivery Carriers for Intratumoral Chemotherapy

出版	University of Florida, 2007
URL	http://books.google.com.hk/books?id=ufl_AQAACAAJ&hl=&source=gbs_api

註釋Optimized DNA-MS syntheses produced particles with narrow and normal size distributions in the 50nm to 5 micron diameter size range. In aqueous dispersions approximately 200% swelling was observed with dispersion stability for more than 48 hours. Typical process conditions included a 1550rpm initial mixing speed and particle filtration through 20 micron filters to facilitate preparation. DNA-MS were in situ loaded during synthesis for the first time with mitoxantrone, 5- fluorouracil, and methotrexate. DNA-MS drug incorporation was 12%(w/w) for mitoxantrone, 9%(w/w) for methotrexate, and 5%(w/w) for 5-fluorouracil. In vitro drug release into phosphate buffered saline was observed for over 35 days by minimum sink release testing. The effect of gadolinium crosslink concentration on mitoxantrone release was evaluated at molar equivalences in the range of 20% to 120%. The most highly crosslinked DNA-MS exhibited the longest sustained release. The drug efficacy of mitoxantrone loaded DNA-MS was evaluated in vitro using a murine Lewis lung carcinoma cell line and a significant cytotoxic response was found at mitoxantrone doses as low as 1ppm. Drug release properties, DNA biodegradability, and observed cancer cell cytotoxicity of drug loaded DNA-MS suggest that they are appropriate for intratumoral chemotherapy evaluation aimed at improved and less toxic cancer therapy.