The Formulation of Methylene Blue Encapsulated, Tc-99m Labeled Multifunctional Liposomes for Sentinel Lymph Node Imaging and Therapy

Methylene blue (MB) is a commonly used dye which can be used for near-infrared (NIR) imaging and photodynamic therapy (PDT) by producing reactive oxygen species after light exposure, inducing apoptosis. The limiting factor of MB is the poor penetration through the cell membranes. Its decreased cellular uptake can be prevented by encapsulating in drug delivery systems such as liposomes. Additionally, EPR effect of tumor gives chance to enhance accumulation of nanocarriers in target site. METHODS: In this study, nanosized, MB encapsulated, Tc-99m radiolabeled Lipoid S PC: PEG2000-PE: Chol: DTPA-PE and DPPC: PEG2000-PE: Chol: DTPA-PE liposomes were formulated to design multifunctional theranostic nanocarriers for; 1. NIR imaging, 2. Gamma probe detection of SLN and 3. PDT which can provide accurate imaging and therapy helping surgery with a single liposomal system. The characterization of liposomes was performed by measuring particle size, zeta potential, phospholipid content, and encapsulation efficiency. Additionally, in vitro release profile of MB and physical stability were also evaluated for six months at determined time intervals by measuring mean particle size, zeta potential, encapsulation efficiency and phospholipid content of liposomes kept at room temperature (25 ͦC) and 4 ͦC. RESULTS: Tc-99m radiolabeled, nanosized Lipoid S PC: PEG2000-PE: Chol: DTPA-PE and DPPC: PEG2000PE: Chol: DTPA-PE liposomes designated proper particle size (around 100 nm), zeta potential (-9 -13 mV), encapsulation efficiency (around 10%), phospholipid efficiency (around 85-90%) and release profile. Additionally, liposomes were observed stable for 3 months especialy when kept at 4°C. DISCUSSION AND CONCLUSION: MB encapsulated, Tc-99m radiolabeled, nanosized Lipoid S PC: PEG2000-PE: Chol: DTPA-PE and DPPC: PEG2000-PE: Chol: DTPA-PE liposomes were found potential for SLN imaging by gamma probe detection, NIR imaging and PDT. In vitro and in vivo imaging and therapeutic efficiency should be definitely evaluated to give a final desicion and our studies are continuing.