Layer-by-layer engineered polymer capsules for therapeutic delivery

Abstract

Polymer capsules fabricated via layer-by-layer (LbL) assembly have emerged as promising carriers for therapeutic delivery. The versatile assembly technique allows an extensive choice of materials to be incorporated as constituents of the multilayers, which therefore endow capsules with specific properties and functionalities. This chapter describes protocols for fabrication of LbL-engineered poly(methacrylic acid) (PMA) capsules for applications in gene delivery, including (1) synthesis of building blocks, (2) cargo encapsulation, (3) multilayer film formation, (4) surface modification, and (5) cross-linking of multilayer films and dissolution of particle templates. DNA is adsorbed onto positively charged silica particle templates, followed by formation of polymer films via hydrogen-bonded multilayers of thiol-functionalized PMA and poly(N-vinylpyrrolidone) (PVP). The outer polymer membranes can be surface modified with copolymers of PMA and poly(ethylene glycol) (PEG). Upon film stabilization and dissolution of particle templates, disulfide-cross-linked DNA-loaded PMA capsules are obtained, which serve as therapeutic carriers that can degrade and facilitate cargo release in intracellular reducing environment.