Interplay between Molecular Packing, Drug Loading, and Core Cross-Linking in Bottlebrush Copolymer Micelles

Abstract

Amphiphilic copolymers with bottlebrush architecture provide opportunities for the refinement of materials properties that may not be attainable from their linear analogues. In this study, we investigated the effect of polymer architecture on an interplay between molecular packing inside micelle cores, cargo loading, and core crosslinking. Four families of polylactide-b-poly(ethylene oxide) (PLA−PEO) bottlebrush block copolymers with different sidechain arrangements were synthesized by a combination of grafting-through and grafting-from methods. Copolymers with double-graft PLA side chains produced smaller and more uniform micelles than those with single-graft PLA branches. Photoactive coumarin groups, installed at PLA side chain ends, improved paclitaxel loading efficiencies of the copolymer micelles and allowed for the preparation of uniform, core-cross-linked PLA nanoparticles. The highest paclitaxel uptake (up to 30 wt % of the micelle core) was observed for micelles prepared from bottlebrush copolymers with branched PEO side chains, with paclitaxel uptake increasing with the size of PEO side chains. On the other hand, micelle photo-cross-linking efficiency was the highest (up to ∼90%) for copolymers with linear PEO side chains and decreased with increasing size of the hydrophilic headgroup. These trends were attributed to the decrease in molecular packing efficiency inside micelle cores for copolymers with larger and more rigid hydrophilic headgroups. For poorly packed micelles, paclitaxel loading improved core photo-cross-linking efficiencies, suggesting structural rearrangements inside micelles with cargo uptake. Preliminary results also showed that paclitaxel release from bottlebrush micelles was slowed down with increasing degree of core cross-linking.

Dilute solution structure of bottlebrush polymers

“…For example: ROMP was initiated by adding G3 (14.03 mg, 0.02 µmol for n bb = 10) in 0.5 mL of THF. After 30 min, a large readily dissolved in CB, and (ii) CB has a relatively high boiling point compared to other organic solvents, which reduces the effects of solvent evaporation.The viscosity of each solution was measured at 30 • C using one of two Cannon-Fenske HeNe laser with a wavelength of 633 nm and an Avalanche photodiode located at a fixed scattering angle of 90 • relative to the incident laser beam [92][93][94].…”

Dilute Solution Structure of Bottlebrush Polymers

“…The setup consisted of a 4 mW HeNe laser with a wavelength of 633 nm and an Avalanche photodiode located at a fixed scattering angle of 90 • relative to the incident laser beam. [92][93][94] We note that performing scattering at this relatively large wave-vector may introduce some wave-vector dependence on the hydrodynamic radius; however, our results indicate that these measurements are consistent with intrinsic viscosity and computer simulations and thus we do not pursue studying this wave-vector dependence. Bottlebrush samples were diluted in chlorobenzene to concentrations ranging from 4 mg/mL to 12 mg/mL and loaded into glass cuvettes.…”

Syntheses of triblock bottlebrush polymers through sequential ROMPs: Expanding the functionalities of molecular brushes

“…With ζ ‐potential of 9 ± 1 and 19 ± 1 mV, both nanostructures displayed cationic surface characteristics. Based on their chemical compositions and sizes, we hypothesize that the packing mode of B1′ and B2′ triblock brushes within these cationic nanoparticles may differ from conventional amphiphilic diblock brushes . Indeed, the rigid PNB backbone and the strong electrostatic repulsion between the cationic PAEAM grafts in B1′ and B2′ enabled the formation of sophisticated arrays of the hydrophilic P(NB‐ g ‐PEG) and P(NB‐ g ‐PAEAM) segments within the nanoassemblies, which require additional exploration.…”