Preparation and validation of cyclodextrin-based excipients for radioiodinated hypericin applied in a targeted cancer radiotherapy
Preparation and validation of cyclodextrin-based excipients for radioiodinated hypericin applied in a targeted cancer radiotherapy
复制标题
用于靶向癌症放射治疗的放射性碘金丝桃素的环糊精赋形剂的制备和验证。
DOI：
10.1016/j.ijpharm.2021.120393
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发表时间：
2021-03-07
影响因子：
5.8
通讯作者：
He, Xiaoyan
中科院分区：
文献类型：
--
作者：
Li, Yue;Wang, Shuncong;He, Xiaoyan
背景：碘-131标记的金丝桃素(I-131-Hyp)已被用作一种双重靶向泛抗癌策略OncoCiDia中的抗坏死治疗示踪剂。由于安全问题，以前测试过的溶剂二甲基亚砜(DMSO)的广泛使用受到了限制。为了解决这一问题，本研究旨在探索一种临床上可行的赋形剂，用于静脉注射疏水性I-131-Hyp。方法：采用紫外分光光度法评价Hyp在已批准的羟丙基-β-环糊精(HP-β-CD)系列溶液中的溶解度，并选择50%的HP-β-CD进行进一步实验。通过核磁共振成像、单光子发射计算机断层扫描(SPECT)、伽马计数、放射自显影术、荧光显微镜和组织病理学等方法，比较了两种基于HP-β-CD的I-131-Hyp新剂型和基于DMSO的两种新剂型在坏死靶向和生物分布方面的差异。所有制剂中I-131-Hyp的放化纯度均大于90%。体内SPECT和体外放射自显影、荧光显微镜和组织病理学证实了I-131-Hyp在新制剂中的坏死靶向性。结论：含HP-β-CD的I-131-Hyp制剂可作为I-131-Hyp静脉给药的辅料。
Background: Iodine-131 labeled hypericin (I-131-Hyp) has been utilized as a necrosis-avid theragnostic tracer in a dual targeting pan-anticancer strategy called OncoCiDia. Widespread use of previously-tested solvent dimethyl sulfoxide (DMSO) is limited by safety concerns. To tackle this, the present study was designed to explore a clinically feasible excipient for the formulation of the hydrophobic I-131-Hyp for intravenous administration.Method: Solubility of Hyp in serial solutions of already-approved hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was evaluated by UV spectrophotometry and 50% HP-beta-CD was chosen for further experiments. Two novel HP-beta-CD-based formulations of I-131-Hyp were compared with previous DMSO-based formulation, with regards to necrosis-targetability and biodistribution, by magnetic resonance imaging, single-photon emission computed tomography (SPECT), gamma counting, autoradiography, fluorescence microscopy and histopathology.Results: Hyp solubility was enhanced with increasing HP-beta-CD concentrations. The radiochemical purity of I-131-Hyp was higher than 90% in all formulations. The necrosis-targetability of I-131-Hyp in the novel formulations was confirmed in vivo by SPECT and in vitro by autoradiography, fluorescence microscopy and histopathology. The plasma clearance of radioactivity was faster in the novel formulations.Conclusion: The novel I-131-Hyp formulations with HP-beta-CD could be a suitable pharmaceutical excipient for I-131-Hyp for intravenous administration.