02430nas a2200385   4500000000100000008004100001260001600042653001800058653001600076653001400092653001800106653003100124653004500155653001300200653001200213653001800225653001300243653001800256653001500274653002300289653002600312653001000338100002700348700001500375700001400390700001200404700001500416700001100431700001500442245011600457300001100573490000700584520143900591022001402030       2009                            d  c2009 Feb 1510aAzo Compounds10aClofazimine10aDodecanol10aDrug Carriers10aHydrogen-Ion Concentration10aHydrophobic and Hydrophilic Interactions10aMaleates10aMannose10aPolyethylenes10aPolymers10aPotentiometry10aSolubility10aStatic Electricity10aSurface-Active Agents10awater1 aHernandez-Valdepeña I1 aDomurado M1 aCoudane J1 aBraud C1 aBaussard J1 aVert M1 aDomurado D00aNanoaggregates of a random amphiphilic polyanion to carry water-insoluble clofazimine in neutral aqueous media.  a345-510 v363 a<p>Clofazimine, an antibiotic drug active against mycobacteria and used for the treatment of leprosy, is a very weak base insoluble in neutral aqueous media. It may cause rather severe secondary effects. Basically, these two shortcomings can be minimized by combination with a drug carrier. The potential of a polymeric carrier composed of nanosized aggregates formed by hydrophobized poly(methyl vinyl ether-alt-maleic acid) to solubilize clofazimine in neutral aqueous media and to administer it to mice was investigated. This amphiphilic polyanion was synthesized by partial esterification of commercial poly(methyl vinyl ether-alt-maleic anhydride) by dodecanol. An aggregate-forming analog bearing mannose residues aimed at targeting mannose receptors born by macrophages was also synthesized and characterized. In the presence of the aggregates, rather large amounts of clofazimine were compatibilized with neutral aqueous media. Comparison with a water-insoluble neutral dye, namely yellow OB, showed that the apparent solubilization of clofazimine was due to a synergistic combination of electrostatic and hydrophobic interactions and not only to the latter as in the case of yellow OB. Despite its favorable in vitro characteristics, clofazimine entrapped within the lipophilic pockets born by the amphiphilic aggregates exhibited no antibiotic activity after administration to mice infected with Mycobacterium bovis BCG.</p>  a1879-0720