Polymer nanoparticles are key for a wide range of applications, such as nano-reactors, encapsulating agents, and biological drug delivery. The synthesis and self-assembly of block copolymers have been studied previously, but a holistic understanding of how the self-assembly pathway affects the size, shape, and morphology of the polymer nanoparticles has yet to be reported. This work takes a functionalisable block copolymer (polydimethyl acrylamide-b-polydiacetone acrylamide) and synthesises it via Polymerisation Induced Self Assembly (PISA) for a range of block copolymer molecular weights. This results in well-defined block copolymers characterised by gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The PISA syntheses suggest a hydrophobic block length of 100 self-assembles into a mixed morphology of nano-objects, but increasing this to 200 results in pure vesicular phases. The pH and salt concentration were varied to physiological conditions (pH 7.5, 140 mM NaCl), and polymer vesicles persisted at neutral pHs and with added electrolyte concentration. The next step was to investigate alternative self-assembly pathways, such as Thin Film Rehydration (TFR) and Solvent Exchange (SE), with the same block copolymer used for the PISA syntheses. TFR proved to be unsuccessful with the targeted block copolymers at pH 2.5. Differential Scanning Calorimetry (DSC) was employed to identify any phase changes of the block copolymer in the solid state. SE was studied as a potential self-assembly pathway for the block copolymer. Methanol was chosen as a co-solvent, and low methanol (5-15%) SE experiments yielded spherical micelles. Upon increasing the methanol concentration to 50%, cylindrical micelles were observed. Upon methanol evaporation, the PDAMm50-b-PDAAm300 sample produced a mixed phase of vesicles and kinetically trapped spheres. Increasing the pH led to the production of cylindrical micelles and spherical micelles; however, when salt was added, the charge was screened, leading to distorted vesicles. A key finding was that the volume of the hydrophobic block is affected when changing self-assembly conditions, which in turn changes the interfacial curvature of the block copolymer, leading to different morphologies being formed during SE. When methanol is increased to 50%, the added solvent plasticises the hydrophobic block, increasing its volume and decreasing the block-copolymer curvature, leading to worms. When 140 mM of NaCl was added to the SE mixture, this result suggests that the NaCl screens the charge on the polymer enough for the polymer to decrease the hydrophilic volume and reduce the interfacial curvature to form larger order nano-objects such as membrane-bound vesicles.
To better understand the morphological changes occurring during methanol evaporation, a three-hour SE evaporation was undertaken at various pHs and ionic strengths, monitoring the methanol content via benchtop NMR. The main morphological changes were from worms to spherical micelles before aggregation occurred. A membrane directing lipid (POPC) was used with the block copolymer during SE experiments to see if this could alter the morphology towards vesicles. This led to a range of spherical micelles being produced at various POPC block copolymer ratios. The self-assembly pathways studied prove that you can get a variety of morphologies from one starting material.
