pH-sensitive polyketal nanoparticles for drug delivery.

In this work, pH-sensitive nanoparticles based on polyketal copolymer (PK3) were formulated by encapsulating hydrophilic doxorubicin hydrochloride (DOX) and hydrophobic paclitaxel (PTX) into the polymer, respectively. Polyketal PK3 was synthesized by the acetal exchange reaction between 2,2-dimethoxypropane and diols. DOX-loaded nanoparticles were fabricated through a modified double emulsion method and PTX-loaded nanoparticles were obtained by single emulsion method. The results demonstrated that the drug loading content increased with the increase of drug/polymer mass ratio, and PTX was entrapped into PK3 nanoparticles more effectively due to its hydrophobic character and the single emulsion method. The in vitro release behaviors of the DOX-loaded and PTX-loaded nanoparticles exhibited that both DOX and PTX release were pH-dependent, and the release rate was much faster in acid environment than that in neutral environment. The cytotoxicity assay of blank nanoparticles indicated that polyketal copolymer (PK3) was biocompatible and suitable as drug vehicle, while PK3 nanoparticle encapsulating DOX or PTX could kill the cancer cells sufficiently and efficiently. Thus, the pH-sensitive PK3 nanoparticle is a promising carrier for both hydrophilic and hydrophobic anticancer drugs.