Synthesis of Diblock Copolymer Nanoparticles via RAFT Alcoholic Dispersion Polymerization: Effect of Block Copolymer Composition, Molecular Weight, Copolymer Concentration, and Solvent Type on the Final Particle Morphology

Abstract

Various poly(2-hydroxyethyl methacrylate-b-benzyl methacrylate) (PHEMA n –PBzMA m ) and poly(2-hydroxypropyl methacrylate-b-benzyl methacrylate) (PHPMA n –PBzMA m ) nano-objects have been prepared via reversible addition–fragmentation chain transfer (RAFT) alcoholic dispersion polymerization. Using either a PHPMA or PHEMA macro-CTA as a steric stabilizer, chain extension with BzMA was conducted in methanol, ethanol, or isopropanol. In each case, in situ self-assembly is driven by the growing PBzMA chains, which become insoluble in lower alcohols above a certain critical chain length. Empirically, PHPMA macro-CTA proved to be much more effective than PHEMA macro-CTA in such syntheses, since the former conferred higher colloidal stability in alcohol. By constructing two detailed phase diagrams, the final nanoparticle morphology is shown to be sensitive to the DP of the core-forming block (PBzMA), the total solids content, and also the mean DP of the stabilizer block (PHPMA). The latter effect is readily demonstrated for PHPMA macro-CTAs possessing mean DPs of 48 and 63. Using PHPMA48 as a steric stabilizer, a range of nano-objects (spheres, worms or vesicles) can be accessed simply by tuning the DP of the core-forming PBzMA block. In contrast, using the PHPMA63 stabilizer only produces spherical morphologies. Presumably this is because the latter confers more effective steric stabilization, which prevents the efficient fusion of spheres to form worms. Nevertheless the PHPMA63–PBzMA n formulation may still be useful, since it allows access to spherical nanoparticles with tunable mean diameters of 29–100 nm. Such phase diagrams are essential for the reproducible targeting of copolymer morphologies, since they enable mixed phase regions to be avoided and allow the predictable synthesis of pure spheres, worms, or vesicles at a given concentration. Finally, a block copolymer “jellyfish” was observed during these PISA syntheses, which suggests that such intermediates are most likely a generic feature of the in situ conversion of worms into vesicles.

RAFT dispersion polymerization in non-polar solvents: facile production of block copolymer spheres, worms and vesicles in n-alkanes

“…More specifically, the judicious selection of a relatively short macro-CTA enables both 45 worm-like and vesicular morphologies to be obtained ( Figure 1C). Thus the same morphological control previously reported for aqueous and alcoholic formulations can also be achieved for RAFT polymerizations conducted in non-polar solvents, which further demonstrates the universal applicability of such PISA 50 formulations.…”

“…Given that these diblock copolymer nanoparticles can be prepared directly in water at relatively low solution viscosities at up to 25 % solids, such 45 robust surfactant-free formulations appear to offer real potential for various commercial applications, including readily sterilizable gels 15 new vectors for intracellular delivery 27 and novel Pickering emulsifiers. 28 Similarly, RAFT dispersion polymerization in polar solvents 50 such as lower alcohols has been extensively explored by Pan et al, [29][30][31][32][33][34] by Charleux and co-workers, 35,36 and also by our own research group. 25,26 Again, pure spherical, worm-like and vesicular morphologies have all been observed, depending on the targeted diblock composition.…”

“…Representative TEM images obtained for each of the PLMA37-PBzMAx compositions are also shown. The scale bar on each image 50 corresponds to 500 nm. The mean diameter of these spherical diblock copolymer nanoparticles can be systematically increased simply by targeting a higher degree of polymerization (x) for the core-forming PBzMA block.…”

Semi-crystalline diblock copolymer nano-objects prepared via RAFT alcoholic dispersion polymerization of stearyl methacrylate

“…For alcoholic dispersion polymerization formulations, we have examined using PBzMA as the core-forming block. [22][23][24][25][26] For example, a detailed phase diagram has been reported for PDMA-PBzMA diblock copolymers prepared via RAFT dispersion polymerization of BzMA in ethanol. 23 In the present study, this prototypical amorphous core-forming block has been replaced with semi-crystalline poly(stearyl methacrylate) (PSMA).…”

“…[14][15][16][17][18][19][20] This highly attractive approach enables bespoke organic nanoparticles to be prepared directly during the copolymer synthesis at much higher concentrations. The most versatile PISA formulation is based on dispersion polymerization, which can be performed in either water, 21 polar solvents such as alcohols, [22][23][24][25][26][27][28][29][30][31] or non-polar solvents such as n-alkanes. [32][33] In each case, a soluble macromolecular chain transfer agent (macro-CTA) is chain-extended using a soluble vinyl monomer in a suitable solvent that is a non-solvent for the growing second block.…”