Self-assembled polymeric micelles based on THP and THF linkage for pH-responsive drug delivery

Developing smart nanocarriers for drug delivery system is advantageous for many kinds of successful biomedicinal therapy. In this study, we designed an amphiphilic block copolymers containing pH-responsive tetrahydropyran (THP) and tetrahydrofuran (THF) linkage. Their structures were confirmed by ¹H NMR and gel permeation chromatography (GPC). The release rate of encapsulated drugs depends upon the pH value and pH sensitive linkage in the backbone of copolymers. For PLA-THP-PEG micelles the cumulative release amount of doxorubicin (DOX) was 62% at pH 5.0, which is about four times higher than that at pH 7.4. Under the same conditions the release rate for PLA-THF-PEG micelles is a little faster than that of the PLA-THP-PEG micelles. Cellular uptake study demonstrates that DOX-loaded micelles can easily enter the cells and produce the desired pharmacological action and minimizing the side effect of free DOX. These findings indicate that THP and THF linked diblock copolymer micelles is a promising candidate for drug carrier.