Grafted Block Copolymer Nanoassembly Drug Carrier

This project aims to develop a novel drug carrier, in the form of a grafted block copolymer nanoassembly (GNA) created from functional poly(ethylene glycol)-poly(amino acids). The GNAs contain a hydrophilic exterior and a hydrophobic interior, allowing tumor specific delivery of poorly-water soluble anticancer drugs through the enhanced permeability and retention (EPR) effect. The GNAs were prepared by conjugating multiple amphiphilic polymer ‘grafts' bound to a fluorescein-tagged polymer ‘scaffold.' Conjugation reactions of grafts with scaffolds were tested under various conditions with different reaction times, ratios, and concentrations. UV/VIS spectroscopic analysis revealed average grafting yields of 2-3 grafts (260 nm) per scaffold (494 nm) with 53 binding sites. Physiochemical properties of GNAs were evaluated by taking particle size with dynamic light scattering measurements at pH 5.0 and 7.4. Results suggested that GNAs have greater stability than conventional self-assembling nanoassemblies (SNAs). Drug loading experiments were subsequently conducted with GNAs using a model drug (17-allylaminogeldanamycin). Colorimetric quantification showed drug loading of 18% and 48% for GNAs and SNAs, respectively.

GNAs with robust globular structures are envisioned to provide a more facile and efficient delivery paradigm for hydrophobic anticancer drugs than other existing injection vehicles, taking advantage of the EPR effect.