Cytosine arabinoside prodrug designed to bind plasma serum albumin for drug delivery.

Abstract

Rational design of anticancer prodrugs for efficient albumin binding can show distinct advantages in drug delivery in terms of high drug availability, long systemic circulation, potential targeting effect, and enhanced chemotherapy effect. In the present study, we reported a cytosine arabinoside (Ara-C) prodrug which could well formulate in solution and instantly transform into long-circulating nanocomplexes by hitchhiking blood-circulating albumin after i.v. administration. Specifically, Ara-C was conjugated with an albumin-binding maleimide derivative, the resulting Ara-C maleimide caproic acid conjugate (AM) was well formulated in aqueous solution, conferring high albumin-binding ability in vitro albumin-binding studies. Moreover, in vivo fluorescence images of sulfo-cyanine5 maleimide indirectly demonstrated that AM showed better accumulation in tumors, exhibiting superior tumor targeting ability and antitumor activity compared to Ara-C. Such a uniquely developed strategy, integrating high albumin-binding capability, has great potential to be applied in clinical cancer therapy.

• Authors: Wei Wei, Zhonggui He, Jincheng Yang, Mengchi Sun, Jin Sun
• Journal: Drug delivery and translational research (Drug Deliv Transl Res) Vol. 8 Issue 5 Pg. 1162-1170 (10 2018) ISSN: 2190-3948 [Electronic] United States
• PMID: 29748833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caproates
• Maleimides
• Prodrugs
• Serum Albumin
• Cytarabine
• hexanoic acid
• maleimide

Topics

• Administration, Intravenous
• Animals
• Caproates (chemistry)
• Cell Line, Tumor
• Circular Dichroism
• Cytarabine (administration & dosage, chemical synthesis, chemistry, pharmacology)
• Drug Delivery Systems
• Drug Design
• Female
• Maleimides (chemistry)
• Mammary Neoplasms, Experimental (drug therapy, metabolism)
• Mice
• Molecular Docking Simulation
• Prodrugs
• Serum Albumin (metabolism)
• Xenograft Model Antitumor Assays