Synthesis Of Bottle Brush Polymers As Drug Delivery Precursors

Bottle brush polymer is a class of polymer macromolecules composed of main and side chains,whose main chains are connected to high-density polymer side chains through chemical bonds.Due to the unique structure of this polymer macromolecule,it is easier to retain in vivo than linear polymers,so it has the potential for drug loading applications.In this paper,polyethylene glycol monomethyl ether was selected as the substrate to design and synthesize two polymers,mPEG-N₃ and mPEG-Pt BA-N₃;Two new macromonomers,Norb-PEG and Norb-Pt BA-PEG,have been synthesized by cycloaddition of polymers with norbornene derivatives via azide-alkyne cycloaddition;Then three kinds of nano bottle brush polymers with different side chain structures were synthesized by the grafting through method with two novel macromonomers.1.mPEG-Br was synthesized with 2-bromo-2-methylpropionyl bromide using polyethylene glycol monomethyl ether of 5000 Da molecular weight as the substrate.mPEG-N₃（5100 Da）was synthesized by replacing Br with-N₃ in Na N₃.mPEG-Br was synthesized using polyethyleneglycol monomethyl ether with 2000 Da as substrate,and then polymerized with t-BA via ATRP reaction into mPEG-Pt BA-Br.mPEG-Pt BA-Br and Na N₃were used to synthesize mPEG-Pt BA-N₃（5100 Da）.2.Synthesis of norbornene hexanol by reaction of norbornene with6-amino-1-hexanol;Esterification of 4-Pentynoic acid acid with norbornene hexanol introduces an alkynyl group into the norbornene derivative;This derivative reacted with two polymers:mPEG-N₃ and mPEG-Pt BA-N₃,respectively,via click chemistry azide alkyne cycloaddition to generate two macromonomers,Norb-PEG（5400 Da）and Norb-Pt BA-PEG（4400 Da）.And then the macromonomer Norb-Pt BA-PEG was hydrolyzed,and the hydrolyzed macromonomer has a large number of carboxyl groups,which can be used to load magnetic materials or applied as drug loading materials.3.The two macromonomers,Norb-PEG and Norb-Pt BA-PEG,were synthesized by romp reaction into three bottle-brush polymers with different side chain structures:the bottle-brush homopolymer Brush-Norb-PEG,the bottle brush core-shell copolymer Brush-Norb-Pt BA-PEG,and the bottlebrush hybrid copolymer PEG-Brush-Pt BA-PEG.When the molar ratio of catalyst to macromonomer was 1:20,the degree of polymerization of the bottle brush homopolymer Brush-Norb-PEG was 13 and its PDI was 1.33.The degree of polymerization of the bottle brush core-shell copolymer Brush-Norb-Pt BA-PEG was 9,and its PDI was 1.28.The degree of polymerization of the bottle brush hybrid copolymer PEG-Brush-Pt BA-PEG was 13 and its PDI was 1.27.The synthesized three nanoscale bottle brush polymers can be functionalized with a large number of carboxyl groups after hydrolysis of the tert-butyl moieties,which will serve as potential drug binding sites.