Self-assembly of Block and Graft Copolymers in Aerosol Nanoparticles

This study examined how to control the self-assembly of block and graft copolymers during the aerosol process, which produces nanoparticles with phase-separated inner structure and phase dimensions ranging from 3 nm to 30 nm. The nanoparticles were also studied for the possibility of their use as a drug carriers. Block copolymers consist of two or more chemically different polymer blocks covalently bound together. In graft copolymers molecules are bound as side-chains to the copolymer backbone. The chemical differences within the copolymer lead to phase-separation: the different parts of the copolymer segregate into separate nano-sized domains. The aerosol flow reactor method was used to prepare nanoparticles of block and graft copolymers. In this method, a precursor solution containing the copolymers and any additional molecules is atomized into an aerosol reactor. Laminar gas flow carries the aerosol into the reactor, in which the solvent evaporates and the aerosol droplets dry into solid nanoparticles. The studied copolymers were poly(styrene-block-4-vinylpyridine) (PS-b-P4VP), a temperature responsive hydrogel poly(styrene-block-N-isopropylacrylamide-block-styrene) (PS-b-PNIPAm-b-PS), and a graft copolymer poly-L-lysine(dodecylbenzenesulfonic acid) (PLL(DBSA)). Furthermore, studies were conducted on PS-b-PNIPAm-b-PS and PLL(DBSA) as potential drug carriers. The self-assembly within the PS-b-P4VP aerosol nanoparticles depended on the copolymer composition, annealing temperature, and solvent composition. Low CholHS side-chain content in the cylinder-forming P4VP resulted in onion-like particles with single CholHS layers, which were sandwiched between P4VP lamellae. Increasing the CholHS content led to smectic P4VP(CholHS) layers perpendicular to the polymer domain interfaces. The highest content resulted in a breakdown of the onion-like structure. PS-b-PNIPAm-b-PS formed nanoparticles with onion-like, gyroid-like, and spherical inner structures with a PNIPAm matrix and physically cross-linking polystyrene domains. Particles with spherical and gyroid-like morphologies swell considerably in water at 20 °C. The release of the incorporated 1,8-ANS fluorescence probe was fastest with the gyroidal and slowest with the sphere-forming morphology. The releases were faster at 25 °C than at 45 °C. Self-assembly of PLL(DBSA) into alpha-helical or beta-sheet secondary structure was controllable with solvent and temperature. The beta-sheet conformation manifested as ~3 nm thick lamellae on the particle surface while alpha-helix formed worm-like domains in the core. Added drugs budesonide and ketoprofen prevented beta-sheet formation and PLL(DBSA)−drug nanoparticles were in the alpha-helical conformation. Drug release from nanoparticles improved the solubility of the poorly soluble budesonide.