In Vitro pH-Dependent Drug Release from N⁴-(4-Carboxybutyryl)-l-/}-D-arabinofuranosylcytosine and Its Conjugate with Poly-L-lysine or Decylenediamine-dextran T70

Abstract

N 4 -(4-Carboxybutyryl)-l-/l-D-arabinofuranosylcytosine (glu-ara-C), the conjugate of glu-ara-C and poly-L-lysine (PLL), (PLL-glu-ara-C), and the conjugate of glu-ara-C and decylenediamine-dextran T70 (T70-C lo ), (T70-C lo -glu-ara-C), were prepared. Drug regeneration from glu-ara-C and the conjugates was investigated in buffered solutions of pH 4,5, 7,7.4 and 8. The character of the drug release from the conjugates was different from that from glu-ara-C. Namely, the release of l-/?-D-arabinofuranosylcytosine (ara-C) from glu-ara-C was accelerated under both weakly acidic and weakly basic conditions, while it was accelerated only under weakly basic conditions from the conjugates. Overall, the drug release profiles from the conjugates showed similar patterns. However, under neutral and weakly basic conditions, ara-C was regenerated more rapidly from PLL-glu-ara-C than from T70-C lo -glu-ara-C. During the incubation of glu-ara-C and the conjugates under weakly acidic conditions, l-/?-D-arabinofuranosyluracil (ara-U) was detected and its amount increased with time to similar extents. © 1989, The Pharmaceutical Society of Japan. All rights reserved.