PH-sensitive poly(ortho ester urethanes) copolymers with controlled degradation kinetic: Synthesis, characterization, and in vitro evaluation as drug carriers

Abstract

Poly(ortho ester urethanes) (POEUs) copolymers were synthesized via polycondensation between the new ortho ester-based diols and hexamethylene diisocyanate (HDI) or dicyclohexylmethane 4,4′-diisocyanate (HMDI) with flexible or rigid chain, which was introduced to regulate the degradation kinetic of POEUs, and designed as POEU1 or POEU2, respectively. POEU1 and POEU2 could form nanoparticles using an oil-in-water single emulsion, which is named as NP1 and NP2, respectively. In vitro degradation experiment shows that NP1 prepared from POEU1 with flexible chains has a degradation half-life of 5.0h at pH 5.0 whereas NP2 prepared from POEU2 with rigid chains has a degradation half-life of 16.2h. Doxorubicin (DOX) was then loaded into these nanoparticles and designed as NP1/DOX and NP2/DOX for evaluating the antitumor effect. NP1/DOX with faster acid-triggered drug release can be more efficiently internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular tumor spheroids (MCTS), and lead to improved antitumor efficiency.