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The Formulation of Methylene Blue Encapsulated, Tc-99m Labeled Multifunctional Liposomes for Sentinel Lymph Node
1Hacettepe University Faculty of Pharmacy, Department of Radiopharmacy, Ankara, Turkey.
Objectives:
Methylene blue (MB) is a commonly used dye that 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 its poor penetration through cell membranes. Its decreased cellular uptake can be prevented by encapsulation in drug delivery systems such as liposomes. Additionally, the enhanced permeability and retention effect of tumors enables enhanced accumulation of nanocarriers at the target site.
Materials And Methods:
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 sentinel lymph nodes (SLNs), 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, the in vitro release profile of MB and physical stability were also evaluated over 6 months at determined time intervals by measuring the 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:PEG2000-PE:Chol:DTPA-PE liposomes showed suitable particle size (around 100 nm), zeta potential (-9 to -13 mV), encapsulation efficiency (around 10%), phospholipid efficiency (around 85-90%), and release profiles. Additionally, the liposomes found stable for 3 months especially when kept at 4°C.
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 to have 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 enable a final decision and our studies on this research topic are continuing.
