Novel pH-sensitive polyacetal-based block copolymers for controlled drug delivery

The principal aim of this study was to synthesize and characterize pH-sensitive biodegradable triblock copolymers containing a hydrophobic polyacetal segment for controlled drug delivery. Poly(ethylene glycol)–poly(ethyl glyoxylate)–poly(ethylene glycol) (PEG–PEtG–PEG) triblock copolymers with PEG molecular weights 500 (PEtG–PEG500) and 750 (PEtG–PEG750) were synthesized by PEtG end-capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG–PEtG–PEG was characterized by 1H NMR spectroscopy. Molecular weights of PEtG–PEG500 and PEtG–PEG750 were determined to be 2823 and 3387, respectively, by gel permeation chromatography. The polymers with a biodegradable polyacetal block underwent pH-dependent degradation via an acid-catalyzed hydrolysis. Paclitaxel (PTX)-loaded polymeric micelles were prepared by a dialysis method and the amount of PTX incorporated into the polymeric micelle formulations was 45,000 times greater than the water solubility of PTX at room temperature. The polymeric micelles prepared from the amphiphilic PEG–PEtG–PEG triblock copolymers have released the loaded PTX in a pH-dependent manner. The novel PEtG-based amphiphilic block copolymers can find applications for targeted and controlled drug delivery to the acidic environments found in tumors and intracellular compartments.