Amphoteric hydrogel capsules: Multiple encapsulation and release routes

We show that chemical cross-linking of hydrogen-bonded poly(methacrylic acid)/poly(vinylpyrrolidone) (PMAA/PVPON) capsules deposited onto silica core with ethylenediamine (EDA) followed by core dissolution and pH-triggered removal of PVPON produces amphoteric hydrogel hollow capsules, whose walls are composed of cross-linked PMAA and contain amino groups provided by the cross-linker. The capsules exhibit highly reversible swelling at acidic and basic pH values due to excess positive and negative charges in the capsule wall and are of minimum size at pH 5.5. Apart from covalent cross-linking, the hydrogel capsule wall is also stitched through ionic pairing in a wide interval of pH. At pH 5-6, where carboxylic acid groups are protonated, the capsule wall expands ( and hydrogel capsules increase in size) in salt solutions as a result of dissociation of ionic cross-links. In contrast, at pH > 6 and pH < 5, where hydrogel wall acquires charge, salt results in the hydrogel contraction and in a decrease of capsule size. In addition to pH and ionic strength, capsule swelling can be controlled by the number of cross-links achieved through variation of cross-linking time. We also show that these soft hydrogel capsules easily flatten when in contact with a solid surface and that the degree of flattening is governed by the surface and capsule charge and the degree of cross-linking in the capsule wall. Finally, we demonstrate that this pH- and ionic-strength-dependent swelling of hydrogel capsules affords multiple routes for encapsulation and controlled release of macromolecules.