Gradient cross-linked biodegradable polyelectrolyte nanocapsules for intracellular protein drug delivery

Gradient shell cross-linked hollow polyelectrolyte nanocapsules composed of cysteamine conjugated chitosan and dextran sulfate were prepared by layer-by-layer adsorption on beta-cyclodextrin (beta-CD) functionalized silica spheres followed by cross-linking thiols and removal of silica core. This disulfide bond gradient cross-linked nanocapsules combined reduction and pH sensitive. Gradually increased from the inside to the outside of the cross-linking degree, one purpose is to ensure that cross-linking disulfide bond after reduction cleavage still has pH sensitive, on the other hand is to avoid cross-linked contraction of internal damage the crystal and bioactivity of protein drugs. Disulfide cross-linked nanocapsules were used to enhance the physical stability against acidic pH conditions compared to the un-cross-linked ones. Bovine serum albumin, as a model protein drug, was loaded inside nanocapsules. The disulfide bond cross-linked nanocapsules are intended to remain more stable in physiological pH and decrease the loss of protein drugs caused by the gastric cavity, and can release the drugs in the intracellular environment after glutathione reduction.