- This paper describes the preparation and characterization of microencapsulated liposome systems (MELs) for the controlled delivery of liposome-associated macromolecules. Liposomes were encapsulated within microspheres of calcium-crosslinked alginate, with an additional membrane of alginate-poly( L -lysine) (PLL). The membrane permeability to liposomes was highly dependent on PLL molecular weight, concentration and reaction time with the microspheres. Membranes formed from PLL of molecular weights ranging between 25 and 87 kDa retained more than 90% of the liposomes within MELs, while those of PLL of 111 kDa and above allowed liposome release. The release was characterized with an initial liposome burst, followed by a continuous release phase. It is suggested that the burst occurs as a result of membrane rupture upon liquefaction of the internal core of the microsphere, in phosphate-buffered saline. After re-establishment of the membrane, MELs released their liposomes, at a rate determined by the permeability properties of alginate-PLL membranes, and liposome surface charge. Direct imaging of the released media, using cryo-transmission electron microscopy (cryo-TEM), revealed that liposomes maintained their supramolecular structure. MELs, coated with PLL of different molecular weights, showed different liposome release rates, after s.c. injection into mice. Twenty-two days after injection, 71% of liposome-associated radioactivity was recovered in mice injected with MELs coated with 25 kDa, while only 6% was recovered in mice receiving MELs coated with 214 kDa. The release pattern of a model antigen, [ 3 H]-labeled bovine serum albumin, from MELs was correlated with that of liposomes, indicating that the protein is released mainly in the context of liposomes. These studies show the potential of MELs as controlled release systems for liposome-associated macromolecules.