A SYNTHETIC MIMIC OF THE SECRETORY GRANULE FOR DRUG-DELIVERY

Secretory cells contain submicroscopic granules composed of a polyanio nic polymer network that is collapsed owing to the presence of hydroni um ions and weak base cations(1-3). The network is encapsulated within a lipid membrane, and functions as a vehicle for the osmotically iner t storage of a variety of granule-bound endogenous mediator species, s uch as histamine, serotonin and proteases. These species are excreted from the granule and thence from the cell in response to external bioc hemical signals(1-4) Hydrogels that swell and shrink in response to ex ternal stimuli might serve as synthetic analogues of secretory granule s(5,6). Here we describe the systematic engineering of multi-component , environmentally responsive hydrogel microspheres, coated with a lipi d bilayer to mimic more closely the natural secretory granule. These m icrospheres 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. T his system could find use for the triggered release of encapsulated dr ugs in the body.