Acid-labile core-layer–shell polymernanoparticles: modeling particle disintegration and subsequent drug release

Abstract

We present a computational investigation into the encapsulation and release of a drug from acid-labile core-layer–shell polymer nanoparticles. In particular, the nanoparticle consists of a hydrophobic layer sandwiched in between a hydrophilic core and an outer hydrophilic shell. This structure provides an effective enthalpic enclosure for an encapsulated hydrophilic drug. However, the acid-labile bonds can sever as the nanoparticle enters the more acidic environment near an actively growing tumor. As the hydrophobic layer, no longer kept in place by the acid-labile bonds, becomes unstable then holes start to form in the layer. We find that a more hydrophobic intermediate layer encapsulates the drug better and, in a more acidic environment, the hole growth in this intermediate layer is also much faster. It is through these holes that the drug can be released into the surrounding fluid. These smart nanoparticles, therefore, could provide a more efficient and safe means of delivering chemotherapeutic agents preferentially to tumor sites.