Synthesis of Poly(N-vinylpyrrolidone)-Based Polymer Bottlebrushes by ATRPA and RAFT Polymerization: Toward Drug Delivery Application.

Atom transfer radical polyaddition (ATRPA) was utilized herein to synthesize a specific functional polyester. We conducted ATRPA of 4-vinylbenzyl 2-bromo-2-phenylacetate (VBBPA) inimer and successfully obtained a linear type poly(VBBPA) (PVBBPA) polyester with benzylic bromides along the backbone. To obtain a novel amphiphilic polymer bottlebrush, however, the lateral ATRP chain extension of PVBBPA with N-vinyl pyrrolidone (NVP) met the problem of quantitative dimerization. By replacing the bromides to xanthate moieties efficiently, we thus observed a pseudo linear first order reversible addition-fragmentation chain transfer (RAFT) polymerization to obtain novel poly(4-vinylbenzyl-2-phenylacetate)-g-poly(NVP) (PVBPA-g-PNVP) amphiphilic polymer bottlebrushes. The critical micelle concentration (CMC) and particle size of the amphiphilic polymer bottlebrushes were characterized by fluorescence spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM) (CMCs < 0.5 mg/mL; particle sizes = ca. 100 nm). Toward drug delivery application, we examined release profiles using a model drug of Nile red at different pH environments (3, 5, and 7). Eventually, low cytotoxicity and well cell uptake of the Madin-Darby Canine Kidney Epithelial (MDCK) for the polymer bottlebrush micelles were demonstrated.