The suitability of liposomes for the delivery of hydrophobic drugs - A case study with curcumin.

Liposomes are a popular formulation strategy for the delivery of anticancer drugs. While their benefits for formulating hydrophilic anticancer drugs have been clearly shown during the last decades, the suitability of liposomes for the delivery of hydrophobic drugs is questionable. Curcumin is a diphenolic plant compound that is extensively researched for its anticancer properties. It was chosen as a hydrophobic model drug in this study. Due to its low bioavailability, poor solubility and instability in aqueous media it is a highly problematic compound and requires particular formulation techniques. Curcumin liposomes with lipids of different rigidities were comprehensively investigated in respect to their physicochemical properties, their storage and serum stability. In vitro experiments were conducted with common 2D cell models and additionally with multicellular tumor spheroids (MCTS) as a more sophisticated tool to represent the physiology of avascular solid tumors. Our results indicate that liposomes containing the fluid phospholipid dioleoylphosphatidylcholine (DOPC) represent an excellent formulation to enhance the solubility and stability of curcumin. However, in presence of serum or cells, curcumin is rapidly released from the protecting and stabilizing lipid bilayer. Thus, improvement of the in vivo efficacy of curcumin is probably not achieved by using liposomes. Cytotoxicity and uptake experiments showed clearly a reduced effectivity of curcumin liposomes in the 3D cell model in comparison to the 2D model. This not only illustrates the limitations of monolayer cultures in predicting drug and nanocarrier interactions with solid tumors, but also further questions the use of liposomes as a formulation strategy in the treatment of solid tumors with curcumin.