Amanda Pedroso de Morais Flávia, Sonchini Gonçalves Renato, Souza Campanholi Katieli, Martins de França Bruna, Augusto Capeloto Otávio, Lazarin-Bidoia Danielle, Bento Balbinot Rodolfo, Vataru Nakamura Celso, Carlos Malacarne Luis, Caetano Wilker, Hioka Noboru
Department of Chemistry, State University of Maringá, 5790 Colombo Ave., 87020-900 Maringá, PR, Brazil.
Department of Chemistry, State University of Maringá, 5790 Colombo Ave., 87020-900 Maringá, PR, Brazil.
Spectrochim Acta A Mol Biomol Spectrosc. 2021 Mar 5;248:119173. doi: 10.1016/j.saa.2020.119173. Epub 2020 Nov 21.
Hypericin (Hy) compound presents a high photoactivity in photodynamic therapy (PDT), photodiagnosis and theranostics applications. The maintenance of this compound in monomeric form could undermine the potential benefits of its photophysical and photodynamic activity. In this study, we demonstrated that the Hy formulated in a system based on the use of the F127 copolymer and the 1,2-dipalmitoyl-sn-3-glycerol-phosphatidylcholine (DPPC) as micelles, liposomal vesicles and Copolymer-Lipid coated systems, have improved its photophysical properties for many clinical modalities. Based on the results of the triplet state lifetime values (τ), the singlet oxygen quantum yield (ΦO), the fluorescence lifetime (τ) and the fluorescence quantum yield (Φ), all Hy formulations had its photophysical properties described in different models of drug delivery systems (DDS). In addition, the transient spectra profile of those formulations was unaffected by the Hy incorporation process, except for the liposomal system, which demonstrated to be the less stable one by flash photolysis technique. The cytotoxic effects of those formulations were also investigated for CaCo-2 and HaCat cells line. The cytotoxic concentrations for 50% (CC) were 0.56, 1.05, 1.33 and 4.80 µmol L for Copolymer-Lipid/Hy, DPPC/Hy, F127/Hy and ethanol/Hy for CaCo-2 cells, respectively, and 0.69, 2.02, 1.45 and 1.16 µmol L for Copolymer-Lipid/Hy, DPPC/Hy, F127/Hy and ethanol/Hy for HaCat cells, respectively. The F127 copolymer had a significant role in many photophysical parameters determined for Copolymer-Lipid/Hy coated system. Although all those formulations had shown satisfactory results, Copolymer-Lipid/Hy proved to be superior in many aspects, being the most promising formulation for PDT, photodiagnosis and theranostics applications.
金丝桃素（Hy）化合物在光动力疗法（PDT）、光诊断及诊疗一体化应用中表现出较高的光活性。该化合物以单体形式存在可能会削弱其光物理和光动力活性的潜在益处。在本研究中，我们证明，将Hy配制在基于使用F127共聚物和1,2 - 二棕榈酰 - sn - 3 - 甘油 - 磷脂酰胆碱（DPPC）的体系中，制成胶束、脂质体囊泡和共聚物 - 脂质包被体系，可改善其在多种临床模式下的光物理性质。基于三线态寿命值（τ）、单线态氧量子产率（ΦO）、荧光寿命（τ）和荧光量子产率（Φ）的结果，所有Hy制剂在不同的药物递送系统（DDS）模型中均具有其光物理性质。此外，除脂质体体系外，这些制剂的瞬态光谱轮廓不受Hy掺入过程的影响，脂质体体系通过闪光光解技术证明是最不稳定的。还对这些制剂对CaCo - 2和HaCat细胞系的细胞毒性作用进行了研究。对于CaCo - 2细胞，共聚物 - 脂质/Hy、DPPC/Hy、F127/Hy和乙醇/Hy的50%细胞毒性浓度（CC）分别为0.56、1.05、1.33和4.80 μmol/L，对于HaCat细胞分别为0.69、2.02、1.45和1.16 μmol/L。F127共聚物在为共聚物 - 脂质/Hy包被体系测定的许多光物理参数中起重要作用。尽管所有这些制剂均显示出令人满意的结果，但共聚物 - 脂质/Hy在许多方面被证明是优越的，是PDT、光诊断和诊疗一体化应用中最有前景的制剂。
