pH-Triggered Drug Release of Monodispersed P(St-co-DMAEMA) Nanoparticles: Effects of Swelling, Polymer Chain Flexibility and Drug-Polymer Interactions.

Monodispersed pH-sensitive poly(styrene-co-N,N′-dimethylaminoethyl methacrylate) (P(St-co- DMAEMA)) nanoparticles (NPs) were synthesized by emulsion polymerization for use in potential applications in targeted drug delivery to the tumor microenvironment. pH-Sensitive volume swelling and drug release of the NPs with varied St/DMAEMA molar ratios, crosslinking degrees and model drug coumarin-6 loading were explored in vitro to elucidate the pH-sensitive drug release mechanisms. The swelling of the NPs, which accounts for the electrostatic repulsion of protonated tertiary amine groups under acidic conditions, reaches maximum at low pH, low crosslinking density and high DMAEMA content. The NPs undergo a pH-triggered drug release, and under the condition of pH 5 and pH 2, the average release rate during 24 h is 1.5-fold and 3-fold higher than that at physiological pH, respectively. The pH-triggered drug release is related to pH-sensitive swelling, polymer chain flexibility and drug-polymer interaction, and is significantly impacted by the St/DMAEMA molar ratio, degree of crosslinking and drug loading.