Cyclic Graft Copolymer Unimolecular Micelles: Effects of Cyclization on Particle Morphology and Thermoresponsive Behavior.

Rebecca J Williams,Andrew P Dove,Nigel Kirby,Rachel K O'Reilly,Anaïs Pitto-Barry

doi:10.1021/acs.macromol.5b02710

Rebecca J Williams, Andrew P Dove + Show 3 more

Open Access

https://doi.org/10.1021/acs.macromol.5b02710

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Journal: Macromolecules	Publication Date: Mar 17, 2016
Citations: 61	License type: cc-by

Affiliation: University of Warwick, Australian Synchrotron

Abstract

The synthesis of cyclic amphiphilic graft copolymers with a hydrophobic polycarbonate backbone and hydrophilic poly(N-acryloylmorpholine) (PNAM) side arms via a combination of ring-opening polymerization (ROP), cyclization via copper-catalyzed azide–alkyne cycloaddition (CuAAC), and reversible addition–fragmentation chain transfer (RAFT) polymerization is reported. The ability of these cyclic graft copolymers to form unimolecular micelles in water is explored using a combination of light scattering, small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryoTEM) analyses, where particle size was found to increase with increasing PNAM arm length. Further analysis revealed differences in the solution conformations, loading capabilities, and morphologies of the cyclic graft copolymers in comparison to equivalent linear graft copolymer unimolecular micelle analogues. Furthermore, the cyclic and linear graft copolymers were found to exhibit significantly different cloud point temperatures. This study highlights how subtle changes in polymer architecture (linear graft copolymer versus cyclic graft copolymer) can dramatically influence a polymer’s nanostructure and its properties.

Highlights

The function and properties of polymers are inherently linked to their structure; through variation of polymer composition and architecture a wide array of applications can be targeted.[1−3] Among the polymer architectures available in the polymer chemist’s toolbox are star,[4−6] branched,[7−10] and dendritic[11−13] structures as well as single chain polymer nanoparticles (SCNPs),[14−17] all of which have found application as unimolecular micelles for potential use as drug delivery vehicles.[10,13,18−20] These unimolecular particles possess advantages over conventional polymeric micelles prepared via the self-assembly of amphiphilic block copolymers,[21] where as a consequence of their unimolecular nature such particles do not display a critical micelle concentration, cannot disassemble, and demonstrate enhanced robustness toward variations in temperature, pH, and ionic strength
To prepare amphiphilic cyclic graft copolymers, hydrophilic poly(N-acryloylmorpholine) (PNAM) arms were grown from the reversible addition−fragmentation chain transfer (RAFT) chain transfer agent (CTA) groups located on the cyclic polycarbonate backbone using similar conditions to those we previously reported for the preparation of linear graft copolymers (Scheme 2).[52]
A series of amphiphilic cyclic graft copolymers with a hydrophobic polycarbonate backbone and hydrophilic PNAM side arms were prepared via a combination of ring-opening polymerization (ROP), CuAAC cyclization, and RAFT polymerization

Summary

Introduction

The function and properties of polymers are inherently linked to their structure; through variation of polymer composition and architecture a wide array of applications can be targeted.[1−3] Among the polymer architectures available in the polymer chemist’s toolbox are star,[4−6] branched,[7−10] and dendritic[11−13] structures as well as single chain polymer nanoparticles (SCNPs),[14−17] all of which have found application as unimolecular micelles for potential use as drug delivery vehicles.[10,13,18−20] These unimolecular particles possess advantages over conventional polymeric micelles prepared via the self-assembly of amphiphilic block copolymers,[21] where as a consequence of their unimolecular nature such particles do not display a critical micelle concentration, cannot disassemble, and demonstrate enhanced robustness toward variations in temperature, pH, and ionic strength. The molecular weights of the resulting graft copolymers were observed to increase, from Mn = 38.9 to 92.9 kDa, as PNAM arm length as evidenced by SEC analysis (Figure 3 and Table 1).

Results

Conclusion