Controlled release of DNA from poly(vinylpyrrolidone) capsules using cleavable linkers

The design of polymer carriers with tunable degradation and cargo release is fundamental for applications in drug and gene delivery. In this study, we report low-fouling poly(N-vinyl pyrrolidone) (PVPON) capsules assembled via hydrogen bonding and stabilized using covalent cross-linking. We first investigated the effects of pH and ionic strength to optimize the assembly conditions. A model therapeutic cargo (plasmid DNA) was then loaded in the capsules and used for encapsulation and release studies. Two bisazide cross-linkers that contain a disulfide bond, termed PEG₈ (poly(ethylene glycol)) and PEG(16), were employed to stabilize the multilayer films, and used to tune the degradation and cargo release behavior of the capsules in simulated cytoplasmic conditions. The results suggest that PEG₈-stabilized capsules were more efficiently cross-linked, and hence displayed higher plasmid encapsulation. Consequently, the capsules cross-linked with PEG₈ also showed a two-fold reduction in degradation rate. This ability to achieve controlled carrier degradation and cargo release makes these capsules of potential interest for drug and gene delivery.