Enzymatically activated microencapsulated liposomes can provide pulsatile drug release

Abstract

A system for the delayed or pulsed release of biologically active substances was achieved by encapsulating liposomes containing the substance of interest inside microcapsules. The microcapsules retain the liposomes but allow controlled diffusion of the active substance when it is released from the liposomes. Furthermore, by coating the liposomes with phospholipase A 2 (an enzyme that removes an acyl group from the 2 position of phospholipids) before placing them within the microcapsule, a pulsatile release pattern was achieved both in vitro and in vivo. The time of onset of the pulse as well as the release rate can be controlled by the amount of phospholipase A 2 , the molecular weight of the poly( l ‐lysine) that is used to coat the microencapsulated liposomes, and the composition of the phospholipid bilayer membrane. Even at 37°C the system would protect a model enzyme (horseradish peroxidase). When not placed inside the microencapsulated liposomes, the enzyme lost its activity in solution at 37°C in a few days, whereas it retained 40% of the initial activity after 30 days of incubation at 37°C inside the microencapsulated liposomes.—K ibat , P. G.; Igari, Y.; Wheatley, M. A.; Eisen, H. N.; Langer, R. Enzymatically activated microencapsulated liposomes can provide pulsatile drug release. FASEB J. 4: 2533‐2539; 1990.