Double hydrophilic block copolymers PEO‐b‐PGA: Synthesis, application as potential drug carrier and drug release via pH‐sensitive linkage

Abstract

A new type of double hydrophilic block copolymer, poly(ethylene oxide) (PEO)-block-poly(glycerol monoacrylate) (PGA) have been synthesized via atom transfer radical polymerization of solketal acrylate (SA) using PEO-Br as macro-initiator, and subsequent hydrolysis of the acetal-protecting group in 1N HCl solution in THF. The polymerization is of a "living" nature and the copolymers with controlled molecular weight and narrow polydispersity (M(w)/M(n) = 1.01-1.03) were obtained. The complete hydrolysis of the acetal-protecting group was verified by IR and NMR spectroscopies. A hydrophobic fluorescent compound, 1-pyrenecarboxaldehyde, was used as a model drug, which was covalently bound to the PEO-b-PGA block copolymer via a pH-sensitive acetal linkage. The kinetics of the pyrene release was studied in THF/aqueous buffers at pH 5.0 (close to pH in endosomes) and 7.4 (pH of blood plasma) by fluorescent spectroscopy. The pyrene was released much faster at pH 5.0 than that at pH 7.4. The micelle behavior in solutions at pH 5.0 and 7.4 was studied by dynamic light scattering. All results show that this double hydrophilic PEO-b-PGA is a promising candidate for potential application as drug carrier for those carbonyl-containing hydrophobic drugs.