The Formulation of Methylene Blue Encapsulated, Tc-99m Labeled Multifunctional Liposomes for Sentinel Lymph Node Imaging and Therapy/Sentinel Lenf Nodu Goruntuleme ve Tedavisi Icin Metilen Mavisi Enkapsule Edilmis, Tc-99m Isaretli Cok-Fonksiyonlu Lipozomlarin Formulasyonu

• Published in: Turkish Journal of Pharmaceutical Sciences Vol. 17; no. 4; p. 381
• Main Author: Gunay, Mine Silindir
• Format: Journal Article
• Language: English
• Published: Galenos Yayinevi Tic. Ltd 01.08.2020
• Subjects: Apoptosis; Drug delivery systems; Health aspects; Methylene blue; Permeability; Phospholipids; Photochemotherapy; Germany
• ISSN: 1304-530X
• DOI: 10.4274/tjps.galenos.2019.86619

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[degrees]C) and 4[degrees]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[degrees]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. Key words: Sentinel lymph node, methylene blue, theranostic nanomedicine, diagnosis Amac: Metilen mavisi (MV) yakin infrared (NIR) goruntuleme ve foto-dinamik tedavi (PDT) icin, isiga maruziyet sonrasi reaktif oksijen radikalleri ureterek apoptozu indukleyen siklikla kullanilan bir boyadir. MV'nin hucre membranlarindan zayif penetrasyonu etkinligini kisitlayan bir faktordur. Azalmis hucresel alimi lipozomlar gibi ilac tasiyici sistemlere enkapsulasyonu ile onlenebilir. Ek olarak, tumorlerin artmis gecirgenlik ve tutulum ozellikleri nanotasiyicilarin hedef bolgede tutulumunu saglar. Gerec ve Yontemler: Nanoboyutlu, MV enkapsule edilmis, Tc-99m radyo-isaretli Lipoid S PC:PEG2000-PE:Chol:DTPA-PE ve DPPC:PEG2000-PE:Chol:DTPA-PE multifonksiyonel teranostik lipozomlari daha kesin goruntuleme ve cerrahiye yardimci olabilecek tedavi saglayabilmek amaciyla; 1) NIR goruntuleme, 2) sentinel lenf nodlarinin (SLN) gama prob ile tayini ve 3) PDT'yi ayni lipozomal sistemde dizayn edilebilen formulasyonlar olarak hazirlanmistir. Lipozomlarin karakterizasyonu partikul boyutu, zeta potansiyeli, fosfolipit icerigi ve enkapsulasyon etkinligi olculerek yapilmistir. Ayrica, MV'sinin in vitro salim profili ve fiziksel stabilitesi alti aylik surede belirli zaman araliklarinda ortalama partikul boyutu, zeta potansiyeli, enkapsulasyon etkinligi ve fosfolipit icerigi oda sicakliginda (25[degrees]C) ve 4[degrees]C'de olculerek degerlendirilmistir. Bulgular: Tc-99m radyo-isaretli, nanoboyutlu Lipoid S PC:PEG2000-PE:Chol:DTPA-PE ve DPPC:PEG2000-PE:Chol:DTPA-PE lipozomlari uygun partikul boyutu (100 nm civarinda), zeta potansiyeli (-9 mV'den -13 mV'e dek), enkapsulasyon etkinligi (%10 civarinda), fosfolipit etkinligi (%85-90 civarinda) ve salim profili gostermistir. Ayrica, 4[degrees]C'de saklandiklarinda lipozomlar 3 ay boyunca stabil kalmistir. Sonuc: MV enkapsule, Tc-99m radyo-isaretli, nanoboyutlu Lipoid S PC:PEG2000-PE:Chol:DTPA-PE ve DPPC:PEG2000-PE:Chol:DTPA-PE lipozomlarinin SLN'nin gama probla tayin edilebilmesi, NIR goruntuleme ve PDT icin potansiyellerinin oldugu bulunmustur. In vitro ve in vivo goruntuleme ve tedavi etkinliklerinin daha kesin sonuca ulasmak icin degerlendirilmesi gerekmektedir ve bu konudaki calismalarimiz devam etmektedir. Anahtar kelimeler: Sentinel lenf nodu, metilen mavisi, teranostik nanotip, teshis