November 3, 2009
Self-Assembly Approaches toward Directed Drug Delivery: from Patchy Micelles to MAD Nanolayers
Electrostatic and secondary interactions of polyelectrolytes and amphiphilic block copolymers can be used to generate new drug and gene delivery systems capable of controlled release triggered by pH or temperature. The 2D and 3D assembly of drug delivery systems will be addressed, including the generation of responsive, multi-agent thin films for localized targeting and controlled delivery from implant surfaces, and the generation of amphiphilic systems that enable highly controlled presentation of ligand for molecularly targeted chemotherapy agents. The manipulation of the solution assembly behavior of new amphiphilic and charged linear dendritic block copolymers, and their use as gene and drug carriers and in novel biomaterials systems will be described. We explore the role of cluster presentation of ligand on patchy micelles generated by the self-assembly of linear dendritic block copolymers. Key to this approach is the synthesis of new amphiphilic linear peptide-dendritic block copolymers that self-assemble in the solution state to generate stable micelles with highly branched, dense dendritic groups in the exterior shell. Due to the unique nature of the dendritic outer block, these micelles act as vessels with a highly tunable 3D presentation of ligand, enabling the creation of delivery nanoparticles with homo- or heterogeneous surfaces that enable cluster presentation of ligand. On the other hand, the alternating adsorption of oppositely charged molecular species, known as the electrostatic layer-by-layer (LBL) process, is a simple and elegant method of constructing highly tailored ultrathin polymer and organic-inorganic composite thin films. We have utilized this method to develop thin films that can deliver proteins and biologic drugs with highly preserved activity from surfaces with sustained release periods of several days; manipulation of the 2D composition of the thin films can lead to simultaneous or sequential release of different components, resulting in highly tunable multi-agent delivery (MAD) nanolayered release systems.