Studies on the lipase induced degradation of lipid based drug delivery systems

The question whether lipid based — especially triglyceride based — depot systems can undergo biodegradation is despite many in vivo studies still unanswered. In this paper we studied biodegradation processes in vitro by incubating these lipid based systems in buffer media containing lipases. The main degradation product the free fatty acids (FFA) were isolated from the drawn samples and after derivatization analyzed with RP-HPLC. Lipid microparticles showed a rapid biodegradation whereas the complete degradation of compressed implants would take several months or years. For these two systems surface degradation can be stated. Surprisingly lipid based extrudates changed their structure dramatically upon lipase incubation resulting in a breakdown of the lipid matrix and formation of small lipid particles in the µm-range. This sort of bulk-degradation may enable the use of lipid based extrudates for the long term delivery of drugs. However additional in vivo experiments will be necessary to fully characterize these degradation processes.

Graphical abstractSimulation of biodegradation of different lipidic drug delivery systems by lipase incubation. Degradation products analyzed via RP-HPLC were used to assess degradation rates of the systems. SEM analysis shows that special composed systems can collapse into particles in the μm-range.Figure optionsDownload full-size imageDownload as PowerPoint slide