Faculty of Chemical and Metallurgical Engineering, Department of Bioengineering, Yildiz Technical University, Esenler, Istanbul, Turkey.
Faculty of Arts and Sciences, Department of Chemistry, Yildiz Technical University, Esenler, Istanbul, Turkey.
Nanotechnology. 2024 Sep 3;35(47). doi: 10.1088/1361-6528/ad726b.
Drug-loaded polymeric micelles have proven to be highly effective carrier systems for the efficient delivery of hydrophobic photosensitizers (PSs) in photodynamic therapy (PDT). This study introduces the micellization potential of poly(oligoethylene glycol methyl ether methacrylate) (pOEGMA) as a novel approach, utilizing the hydrophobic methacrylate segments of pOEGMA to interact with highly hydrophobic zinc phthalocyanine (ZnPc), thereby forming a potential micellar drug carrier system. The ZnPc molecule was synthesized from phthalonitrile derivatives and its fluorescence, photodegradation, and singlet oxygen quantum yields were determined in various solvents. In solvents such as tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide, the ZnPc compound exhibited the requisite photophysical and photochemical properties for PDT applications. The pOEGMA homopolymer was synthesized via reversible addition-fragmentation chain-transfer polymerization, while ZnPc-loaded pOEGMA micelles were prepared using the nanoprecipitation method. Characterization of the pOEGMA, ZnPc, and micelles was conducted using FTIR,H-NMR, dynamic light scattering, matrix-assisted laser desorption/ionization time-of-flight mass spectrometries, gel permeation chromatography, and transmission electron microscopy. The critical micelle concentration was determined to be 0.027 mg mlusing fluorescence spectrometry. The drug loading and encapsulation efficiencies of the ZnPc-loaded micelles were calculated to be 0.67% and 0.47%, respectively. Additionally, the release performance of ZnPc from pOEGMA micelles was monitored over a period of nearly 10 d, while the lyophilized micelles exhibited stability for 3 months. Lastly, the ZnPc-loaded micelles were more biocompatible than ZnPc on L929 cell line. The results suggest that the pOEGMA homopolymer possesses the capability to micellize through its methacrylate segments when interacting with highly hydrophobic molecules, presenting a promising avenue for enhancing the delivery efficiency of hydrophobic PSs in PDT. Moreover, it was also deciphered that obtained formulations were highly biocompatible according to cytotoxicity results and could be safely employed as drug delivery systems in further applications.
载药聚合物胶束已被证明是高效传递疏水性光敏剂（PS）的载体系统，在光动力疗法（PDT）中具有重要应用。本研究提出了一种新的方法，即利用聚（聚乙二醇甲基醚甲基丙烯酸酯）（pOEGMA）的疏水性甲基丙烯酸酯段与高度疏水性锌酞菁（ZnPc）相互作用，从而形成潜在的胶束药物载体系统。ZnPc 分子由邻苯二腈衍生物合成，其在各种溶剂中的荧光、光降解和单线态氧量子产率被测定。在四氢呋喃、二甲基亚砜和 N，N-二甲基甲酰胺等溶剂中，ZnPc 化合物表现出适用于 PDT 应用的必要光物理和光化学性质。pOEGMA 均聚物通过可逆加成-断裂链转移聚合合成，而负载 ZnPc 的 pOEGMA 胶束则通过纳米沉淀法制备。使用傅里叶变换红外光谱（FTIR）、H-NMR、动态光散射、基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）、凝胶渗透色谱（GPC）和透射电子显微镜（TEM）对 pOEGMA、ZnPc 和胶束进行了表征。使用荧光光谱法确定临界胶束浓度为 0.027mg/ml。负载 ZnPc 的胶束的载药量和包封效率分别计算为 0.67%和 0.47%。此外，在近 10 天的时间内监测了 ZnPc 从 pOEGMA 胶束中的释放性能，而冻干胶束在 3 个月内保持稳定。最后，负载 ZnPc 的胶束比 L929 细胞系上的 ZnPc 更具生物相容性。结果表明，pOEGMA 均聚物通过其与高度疏水分子相互作用的甲基丙烯酸酯段具有胶束化能力，为提高 PDT 中疏水性 PS 的传递效率提供了有前景的途径。此外，根据细胞毒性结果表明，所获得的制剂具有高度的生物相容性，可安全地用作进一步应用的药物传递系统。
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