A synthetic mimic of the secretory granule for drug delivery

Secretory cells contain submicroscopic granules composed of a polyanionic polymer network that is collapsed owing to the presence of hydronium ions and weak base cations. The network is encapsulated within a lipid membrane, and functions as a vehicle for the osmotically inert storage of a variety of granule-bound endogenous mediator species, such as histamine, serotonin and proteases. These species are excreted from the granule and thence from the cell in response to external biochemical signals. Hydrogels that swell and shrink in response to external stimuli might serve as synthetic analogues of secretory granules. Here we describe the systematic engineering of multi-component, environmentally responsive hydrogel microspheres, coated with a lipid bilayer to mimic more closely the natural secretory granule. These microspheres exhibit pH- and ion-dependent volume phase transitions and ion-sensitive exchange of bound cations when the encapsulating lipid membrane is porated. We stimulated poration electrically in individual microgel particles immobilized and manipulated with a micropipette. This system could find use for the triggered release of encapsulated drugs in the body.