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.

Low-fouling poly(N-vinyl pyrrolidone) capsules with engineered degradable properties.

We report the assembly of low-fouling polymer capsules with engineered deconstruction properties by using a combination of layer-by-layer (LbL) assembly and click chemistry. Preformed, hydrogen-bonded multilayers of alkyne-functionalized poly(N-vinyl pyrrolidone) (PVPON(Alk)) and poly(methacrylic acid) (PMA) assembled at pH 4 on silica particles were cross-linked with a bisazide linker (containing a disulfide link) through alkyne-azide click chemistry. Following dissolution of the silica template particles, and altering the solution pH to 7.2 to disrupt hydrogen bonding between PVPON(Alk) and PMA to effect removal of PMA, stable, cross-linked PVPON capsules were obtained. The presence of the disulfide bond in the bisazide linker endowed the PVPON capsules with degradable characteristics under model intracellular conditions. The capsules deconstructed within 4 h in the presence of 5 mM glutathione. The cross-linked PVPON(Alk) multilayers (assembled on silica particles) were low-fouling to a range of proteins, including fibrinogen, lysozyme, immunoglobulin G, and bovine serum albumin. Further, MTT assays showed that the PVPON capsules had no effect on the proliferation of cells from a human colon cancer cell line (LIM1899), indicating negligible cytotoxicity toward the LIM1899 cells. The low-fouling, degradable, and low cytotoxicity characteristics of the PVPON capsules makes them attractive as a platform for the development of advanced therapeutic delivery systems.