The effect of lipase on the release of naltrexone from triglyceride-coated cellulose acetate phthalate microspheres.
The ultimate objective of this work is to develop a device that can be triggered by morphine to release naltrexone. In this device, naltrexone is dispersed in cellulose acetate phthalate microspheres which are then spray-coated with a trilaurin protective coating. The microspheres are contained within a macroporous cylinder which also contains a reversibly inactivated lipase. This enzyme in its inactive state is unable to remove the protective coating but in its active state is able to do so. Inactivation is achieved by the covalent attachment of morphine followed by complexation with a morphine antibody. Triggering is accomplished by the displacement of the lipase-morphine conjugate from the antibody. In this phase we have investigated the effect of lipase on the release of naltrexone from trilaurin-coated microspheres and found that the coated microspheres are stable in a pH 7.4 phosphate buffer at 37 degrees C for at least 1 month, but release 80% of the incorporated naltrexone in one hour when 100 mg of capsules in 5 mL buffer are exposed to 25 micrograms of lipase.
Tefft
J A
JA
Controlled Release and Biomedical Polymers Department, SRI International, Menlo Park, California 94025.
Roskos
K V
KV
Heller
J
J
D001672:Biocompatible Materials; D002482:Cellulose / Q000031:analogs & derivatives; D016503:Drug Delivery Systems; D004789:Enzyme Activation; D008049:Lipase / Q000037:antagonists & inhibitors; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009020:Morphine; D009271:Naltrexone / Q000008:administration & dosage*; D014280:Triglycerides
D001672:Biocompatible Materials; D014280:Triglycerides; D009271:Naltrexone; D009020:Morphine; C004565:trilaurin; D002482:Cellulose; C011708:cellulose acetate phthalate; D008049:Lipase