Abstract

Focusing on the development of a nanometer scale carrier in the drug-delivery-system for cancer therapy, we prepared a lipid nano-emulsion (LNE) from a lipid mixture of soybean oil (SO), phosphatidylcholine (PC) and sodium palmitate as a vehicle for chloroaluminum phthalocyanine (ClAlPC), a photosensitizer used for the photodynamic treatment of cancer. To elucidate its distribution in our LNE formulation, we proposed a modified three-phase (SO core, PC monolayer and water phase) model using the molar partition coefficients (Kps) of ClAlPC in LNE/water and PC small unilamellar vesicle (PC SUV)/water systems. In the presence of LNE or PC SUV, a spectrophotometric absorption maximum due to monomeric ClAlPC was observed, but was absent in buffered solution because of its property of selfaggregation in aqueous media, showing that the partitioned ClAlPC exists as a monomer. The Kp values of ClAlPC were calculated using the intensity of the absorption maximum in the second derivative spectra. Although the Kp values showed ClAlPC concentration dependence due to the association of ClAlPC in the water phase, they were on the order of 104 for the concentrations of 1 – 5 μM ClAlPC, indicating that our LNE having a lipid concentration of 72 mM can encapsulate 95 – 99% of the spiked ClAlPC. Furthermore, most of ClAlPC was found to be located in the PC monolayer surrounding the SO droplets in the LNE. These results indicate that the PC monolayer not only acts as a water-oil interface, but also stores monomeric ClAlPC in our LNE effectively.

Keywords: Lipid nano-emulsion, Chloroaluminum phthalocyanine, Second-derivative spectrophotometry, Liposome, Threephase model, Distribution, EPR, lipid emulsion, LE, phosphatidylcholine, LNE, ClAlPC, photodynamic therapy, high-density lipoprotein, DMSO, dynamic light scattering, DLS, submicron particle analyzer, phosphovanadomolybdate method, spectrophotometer, Hitachi U-3310, Savitzky-Golay method, photosensitizer