Development of a cell-targeted liposome formulation for small cell lung cancer

Abstract

Lung cancer is one of the most common cancers with small cell lung cancer (SCLC) representing 18% of the total lung cancer diagnoses. Conventional treatments include the administration of high dosages of cisplatin, but as most anti-cancer agents, this drug is not targeted which causes toxicity and undesirable severe side-effects which limit its clinical application. Liposome-based formulations have been recently exploited for improving the delivery and therapeutic effect of cisplatin (Lipoplatin®). In this study, we sought to generate a targeted liposomal formulation. The gastrin releasing peptide (GRP) receptor is over-expressed on many cancer cells including SCLC. A conventional liposomal cisplatin formulation was modified by adding a GRP receptor agonist to a pegylated lipid which was then inserted into pre-formed liposomes. However, the biological activity of peptide-modified liposomal cisplatin was comparable to the control liposomes when tested on GRP receptor positive SCLC cells (NCI-H345), and GRP receptor negative control cells (A549), using the MTS assay. ICP-AES analysis of cisplatin encapsulation efficiency showed encapsulation to be decreased in the targeted formulation. Fluorescence liposomes were also prepared to evaluate the uptake of the cells, using carboxyfluorescein as fluorescence agent. Results shows higher uptake by target- liposomes.