Lipodisks for Dual Delivery of SN-38 and Melittin

Abstract: The use of drug delivery systems based on liposomes or lipodisks as nanocarriers have been proven to have several advantages compared to conventional chemotherapy when drug is administered in free form. Lipodisks are not as well studied as liposomes, but can be reliably produced with a smaller size which is an important factor for efficient accumulation at the target site and penetration of tumor tissue. The active metabolite of irinotecan, SN-38, which has been used in cancer treatment for many years, has high cytotoxicity and its hydrophobic nature makes it a good candidate for encapsulating in lipodisks. Melittin, an anti-cancer agent with a membranolytic activity, has been established to have high affinity to lipodisks, preferably binding to the outside rim. The aim of this thesis was to investigate the potential for lipodisks to be used as nanocarriers for dual drug delivery of SN-38 and melittin. This was achieved by first developing a protocol for producing SN-38 loaded lipodisks. Furthermore, melittin binding to empty and SN-38 loaded lipodisks was investigated to determine if the SN-38 would interfere with the binding of melittin. Based on the results, SN-38 can be reliably encapsulated in lipodisks with an average encapsulation efficiency of 78%. The drug release in buffer for these lipodisks was determined to be 73% after 48h. From the melittin binding experiments, it was determined that melittin had a high affinity to empty lipodisks and a high maximum binding capacity. The results from the binding of melittin to SN-38 loaded lipodisks showed that melittin did bind to the lipodisks but the binding must be further investigated through repeated measurements.