Formation of platinum (II) as a six member ring for sustained polymeric delivery

Abstract

A new pH-activated polymer chelate of cisplatin was synthesized using a scalable and green aqueous technique. Synthesis of the chelate was based on formation of a 6-member ring of platinum(II) with acetyl-homo-Lysine (Ac-homo-Lys), which was accomplished under completely aqueous conditions using a traceless photocleavable protection chemistry. Synthesis preceded by, first, amidation of a photocaged homo-Ac-Lys with hyaluronic acid (HA) in water using a p-hydroxyphenacyl (pHP) group as the photoremovable protecting group, followed by reaction of cisplatin (diaqua form) in water to form the reversible chelate. Platinum drug release was pH rate controlled, with more rapid release (t_1/2 20 h) at acidic pH similar to the tumor microenvironment yet slower release (t_1/2 35 h) at normal physiological pH.

Keywords: Cisplatin chemotherapy; Five-membered ring; Homo-lysine; Hyaluronic acid; Lysine; Six-membered ring.