A morphine-triggered delivery system useful in the treatment of heroin addiction

The ultimate objective of this work is to develop a device that can be triggered by morphine to release naltrexone. Two device configurations are described. In one configuration, naltrexone is dispersed in cellulose acetate phthalate microspheres which are then spray-coated with trilaurin. In the other configuration, naltrexone is dispersed in an n-octyl half ester of methyl vinyl ether and maleic anhydride copolymer and the mixture fabricated into a disk which is then coated with trilaurin. The microspheres are designed to release naltrexone abruptly while the disks are designed to release naltrexone at a constant rate over a two week period. The microspheres, or the disk along with a reversibly inactivated lipase are placed inside a semipermeable membrane that allows free passage of morphine and naltrexone but excludes the higher molecular weight components of the device. Reversible inactivation of lipase is achieved by covalent attachment of morphine and complexing with morphine antibody. Activation of the device occurs by diffusion of morphine into the device and displacing the lipase-morphine conjugate from the antibody. The activated lipase then removes the trilaurin protective coating, thus triggering naltrexone release.