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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Preparation and in vitro evaluation of magnetic microsphere-methotrexate conjugate drug delivery systems.

Magnetic microsphere-methoxtrexate (MM-MTX) conjugates prepared by several different methods were analyzed for their suitability for in vivo use. MM-MTX were prepared by the following methods: (A) reaction of MTX with poly(ethylene glycol) 1500 (PEG) to form a poly(ethylene glycol)-methotrexate conjugate (PEGMTX) which was then added to a ferrous/ferric ion salt solution to give MM-MTX I; (B) reaction of ferrous/ferric ion salts with PEG to give a ferromagnetic polymer complex which was then coupled with MTX to give MM-MTX II; (C) MM-MTX IIIA were prepared by reacting MTX with amino-terminated magnetic microspheres, commercially available, in the presence of 1-ethyl-3,3-bis(methylamino)propylcarbodiimide (EDCI); (D) reaction of aminohexanol with di-tert-butyl dicarbonate to form an [N-(tert-butoxycarbonyl)amino]hexanol (t-Boc-AH), which was then coupled with MTX in the presence of 1,3-dicyclohexylcarbodiimide and 4-pyrrolidinopyridine to give a t-Boc-AH-MTX conjugate, which was then saturated with hydrogen chloride to give an aminohexanol-methotrexate (AH-MTX) conjugate. MM-MTX IIIB were then prepared by reacting AH-MTX with carboxyl-terminated magnetic microspheres, commercially available, in the presence of EDCI and 4-(dimethylamino)pyridine. The identity of MTX conjugates was confirmed using ultraviolet, infrared, and nuclear magnetic resonance spectroscopy. Drug content of the magnetic microsphere-methotrexate conjugates as determined by HPLC was 0.45% (w/w), 4.0% (w/w), and 6.3% (w/w) MTX for MM-MTX I, MM-MTX II, and MM-MTX IIIB, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

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