KCS

Over the past decades, biocompatible polymers have been proposed as a delivery platform for the improved aqueous solubility and reduced off-target toxicity for small-molecule drugs, allowing for the selected delivery to the disease sites. Although such delivery systems have been demonstrated to possess great potential to decrease the toxic side effects often associated with conventional chemotherapy, successes have been limited due in part to the limited colloidal stability and specific triggers to release the encapsulated drug molecules under predefined biochemical condition. To overcome these challenges, we have developed two strategies based on the chemically modified natural polysaccharides such as chitosan and artificial synthetic block-copolymers for polymeric excipients to encapsulate cisplatin pharmacophore (Pt^II) as a model drug. For stability enhancement and inorganic drug-conjugation, native chitosan was modified with small poly(ethylene glycol) and malonic acid, which was then subjected to bind the aqua derivatives of Pt^II species. As a synthetic polymer-based platform, a series of poly(ethylene glycol)-b-poly(acrylic acid) copolymers have been synthesized via nitroxide-mediated radical polymerization with chemically modified alkoxyamine initiator, which was then employed to incorporate the chemotherapeutic Pt^II compounds. Both approaches lead to the formation of self-assembled nanoscale structures in aqueous solution, which possess the grafted polymer chains cross-linked via Pt^II-coordination and hydrophobic interactions, allowing for the enhanced colloidal stability and pH-sensitive reversible release of Pt^II species. The physicochemical properties of the resulting materials will be demonstrated.