Evaluation of the conjugate between N4-(4-carboxybutyryl)-1-beta-D-arabinofuranosylcytosine and chitosan as a macromolecular prodrug of 1-beta-D-arabinofuranosylcytosine.

Abstract

The conjugate of N4-(4-carboxybutyryl)-1-beta-D-arabinofuranosylcytosine (glu-ara-C) with chitosan, named chi-glu-ara-C, was prepared and evaluated on its utility as a macromolecular prodrug. 1-beta-D-Arabinofuranosylcytosine (ara-C) was predominantly regenerated gradually from chi-glu-ara-C in 1/15 M phosphate buffer, pH 7.4, at 37 degrees C, and its amount after 7 d incubation was 56% (w/w). The antitumor effect was evaluated by an increase in the lifespan (ILS) of the mice bearing P388 leukemia at the single administration at 24 h after inoculation. Ara-C exhibited an ILS of 3.4% at a dose of 100 mg/kg, and the survival time was not significantly different from that of the control. However, chi-glu-ara-C showed an ILS of 60.7% at a dose of 88 mg eq ara-C/kg, and the survival time was significantly different from that of the control. Chitosan and chi-glu-ara-C were observed to cause the side effects judged from the body weight loss to a certain extent. However, chi-glu-ara-C was recognized to be useful because of its effectiveness.

• Authors: H Ichikawa, H Onishi, T Takahata, Y Machida, T Nagai
• Journal: Drug design and discovery (Drug Des Discov) Vol. 10 Issue 4 Pg. 343-53 ( 1993) ISSN: 1055-9612 [Print] Switzerland
• PMID: 8148473 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Prodrugs
• chitosan-N(4)-(4-carboxybutyryl)-1-arabinofuranosylcytosine conjugate
• Cytarabine
• Chitin
• N(4)-(4-carboxybutyryl)-1-beta-arabinofuranosylcytosine
• Chitosan

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology, toxicity)
• Body Weight (drug effects)
• Chitin (analogs & derivatives, chemical synthesis, chemistry, pharmacology, toxicity)
• Chitosan
• Cytarabine (analogs & derivatives, chemical synthesis, pharmacology, toxicity)
• Drug Carriers
• Hydrogen-Ion Concentration
• Leukemia P388 (drug therapy)
• Longevity (drug effects)
• Magnetic Resonance Spectroscopy
• Mice
• Mice, Inbred Strains
• Prodrugs (chemical synthesis)
• Spectrophotometry, Ultraviolet