(43c) Solution Assemblies of Novel Amphiphilic Block Copolymers for Drug Delivery

The biomedical field utilizes solution assemblies of block copolymers as drug and gene delivery vehicles, imaging agents, and diagnostic tools.  Specifically, amphiphilic block copolymers form solution assemblies of a variety of structures based on the molecular weight and volume fraction of each component; these structures include spherical micelles, cylindrical micelles, and vesicles, which can be used as drug delivery vehicles.  The increased stability, synthetic versatility, and potential for post-assembly functionalization make these macromolecular assemblies particularly attractive for biological applications. In particular, the incorporation of active targeting groups, through post-assembly functionalization, can be used to promote cell-specific interactions in vitro and in vivo and hence enable disease-targeting therapies.  Previous work showed that targeting ligands buried at the hydrophilic/hydrophobic interface were not active whereas peripheral ligands promoted rapid clearance from the body.  Therefore, polymer-peptide conjugates, prepared using a combination of anionic ring-opening polymerization and solid phase peptide synthesis, with manipulated ligand display enabled decoupled prolonged circulation and active targeting for enhanced and effective drug delivery.  This study revealed the influence of the targeting ligand location on the solution assembly, directed cellular internalization, and in vivo circulation time, and analyzed the efficiency of hydrophobic drug encapsulation and delivery.  The series of amphiphilic block copolymers studied herein present a methodology for decoupling prolonged circulation and targeted therapeutic delivery, which could prove pivotal for effective drug delivery strategies.