Synthesis and application of pH-sensitive linkers in amphiphilic block copolymer

A series of acid cleavable linkers based on tetrahydropyran/tetrahydrofuran (THP/THF) ether were synthesized, in which both of the two terminals are active group which is easy to react with other compounds. The structures for these linkers 1a and 1b were confirmed by ¹H NMR, ¹³C NMR, HRMS, and IR. Model compound containing THP linkage was synthesized. Furthermore a pH-responsive amphiphilic diblock copolymer containing tetrahydrofuran (THF) linkage in which hydrophilic segment was poly(ethylene glycol) (PEG) and hydrophobic segment was hydrophobic polylactic acid (PLA) was synthesized and characterized by ¹H NMR, IR and gel permeation chromatography (GPC). The size, stability and critical micelle concentration (CMC) of diblock copolymer micelle were also evaluated. The preliminary experimental results show that the acid sensitive amphiphilic diblock copolymer micelle is a potential alternative for future drug delivery.