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 microm-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.
Schwab
Martin
M
Ludwig-Maximilians-University Munich, Butenandtstr.5, 81377 Munich, Germany. martin.schwab@cup.uni-muenchen.de
Sax
Gerhard
G
Schulze
Sandra
S
Winter
Gerhard
G
D000818:Animals; D002021:Buffers; D002626:Chemistry, Pharmaceutical; D001517:Coleoptera / Q000201:enzymology; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry; D011549:Pseudomonas / Q000201:enzymology; D013678:Technology, Pharmaceutical; D013696:Temperature; D014280:Triglycerides / Q000378:metabolism
D002021:Buffers; D004337:Drug Carriers; D008055:Lipids; D010710:Phosphates; D014280:Triglycerides; D008049:Lipase