In vitro investigation of lipid implants as a controlled release system for interleukin-18.

Operating on the inductive and effective phases of an anti-tumor immune response and uncovering pivotal functions that may reduce cancer cell growth, interleukin-18 (IL-18) appears to be an attractive candidate for the sustained local adjuvant immunotherapeutic treatment of brain gliomas. The objective of this work was to develop IL-18 loaded lipid implants as a controlled delivery system. For the preparation of protein loaded triglyceride matrix material, a solid-in-oil (s/o) dispersion technique was chosen for which protein particles in the micrometer range were first prepared by co-lyophilization with polyethylene glycol (PEG). Implants of 1 mm diameter, 1.8 mm height and 1.8 mg weight were manufactured by compression of the powder mixture in a specially designed powder compacting tool. The in vitro release behavior of 125I-Bolton-Hunter-radiolabeled IL-18 was assessed in a continuous-flow system. A cell culture assay was established for the determination of bioactivity of released IL-18. Implants showed a continuous release of 10-100 ng IL-18 per day for 12 days. A progressive integrity loss was observed with ongoing release, which would be related to protein degradation during incubation. The initially released fraction proved complete retention of bioactivity, indicating that the manufacturing procedure had no detrimental effects on protein stability.