Synthesis and characterization of a multi-arm poly(acrylic acid) star polymer for application in sustained delivery of cisplatin and a nitric oxide prodrug

摘要

Functionalized polymeric nanocarriers have been recognized as drug delivery platforms for delivering therapeutic concentrations of chemotherapies. Of this category, star-shaped multiarm polymers are emerging candidates for targeted delivery of anti-cancer drugs, due to their compact structure, narrow size distribution, large surface area and high water solubility. In this study, we synthesized a multi-arm poly(acrylic acid) star polymer via MADIX/RAFT polymerization and characterized it using NMR and size exclusion chromatography. The poly(acrylic acid) star polymer demonstrated excellent water solubility and extremely low viscosity, making it highly suited for targeted drug delivery. Subsequently, we selected a hydrophilic drug, cisplatin, and a hydrophobic nitric oxide-donating prodrug, O²-(2,4-dinitrophenyl) 1-[4-(2-hydroxy)ethyl]-3-methylpiperazin-1-yl]diazen-1-ium-1,2-diolate, as two model compounds to evaluate the feasibility of using poly(acrylic acid) star polymers for delivery of chemotherapeutics. After synthesizing and characterizing two poly(acrylic acid) star polymer-based nanoconjugates, poly(acrylic acid)-cisplatin (acid-Pt) and poly(acrylic acid)-nitric oxide prodrug (acid-NO), the in vitro drug release kinetics of both acid-Pt and acid-NO were determined at physiological conditions. In summary, we have designed and evaluated a polymeric nanocarrier for sustained-delivery of chemotherapies, either as a single treatment or a combination therapy regimen.