Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstraße 48, 48149 Muenster, Germany.
Institute of Pharmaceutical and Medicinal Chemistry, University of Muenster, Corrensstraße 48, 48149 Muenster, Germany.
Int J Pharm. 2020 May 30;582:119347. doi: 10.1016/j.ijpharm.2020.119347. Epub 2020 Apr 18.
Nanoparticle albumin-bound (nab)-technology is an industrial applicable manufacturing method for the preparation of albumin-based drug carriers of poorly water-soluble drugs. In the present study the advantages of nanotechnology, albumin as an endogenous protein with the capability of high tumor enrichment and the selective light activation of the photosensitizer Temoporfin (mTHPC) were combined to a new delivery system for oncological use. The herewith provided well-established photodynamic therapy may enable a beneficial alternative for the treatment of solid tumors. In the present study a reproducible method for the preparation of stable mTHPC-albumin nanoparticles via nab-technology was established. The nanoparticles were physicochemically characterized with regard to particle size and size distribution and the impact of this preparation method on nanoparticle as well as mTHPC stability was investigated. Nanoparticles with improved colloidal stability over a broad pH range and in the presence of physiological NaCl concentrations were achieved in high yield. Due to high pressure homogenization a certain oxidative decay of mTHPC was observed. Cell culture experiments revealed an effective cellular uptake of mTHPC in a cholangiocarcinoma cell line (TFK-1). After light-activation high cytotoxicity was shown for photosensitizer loaded nanoparticles enabling the application of the proposed formulation in photodynamic therapy.
纳米白蛋白结合（nab）技术是一种工业适用的制造方法，用于制备基于白蛋白的难溶性药物的药物载体。在本研究中，纳米技术的优势、白蛋白作为一种具有高肿瘤富集能力的内源性蛋白质以及光敏剂 Temoporfin（mTHPC）的选择性光激活被结合到一种新的用于肿瘤治疗的递药系统中。这里提供的成熟的光动力疗法可能为治疗实体瘤提供一种有益的替代方法。在本研究中，通过 nab 技术建立了一种可重现的制备稳定 mTHPC-白蛋白纳米颗粒的方法。对纳米颗粒的物理化学性质进行了研究，包括粒径和粒径分布，并研究了这种制备方法对纳米颗粒和 mTHPC 稳定性的影响。在宽 pH 范围和生理 NaCl 浓度存在下，纳米颗粒具有良好的胶体稳定性，产率高。由于高压匀浆，观察到 mTHPC 发生一定程度的氧化降解。细胞培养实验显示，载 mTHPC 的纳米颗粒在胆管癌细胞系（TFK-1）中具有有效的细胞摄取。光激活后，负载光敏剂的纳米颗粒表现出高细胞毒性，这使得所提出的制剂能够应用于光动力疗法。
