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CTP修饰丹参酮IIA胶束的处方优化、表征及其心肌靶向保护作用

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中草药 | 药剂与工艺 2026,57(4): 1275-1285

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中草药 |药剂与工艺 2026 , 57 (4) : 1275 -1285

CTP修饰丹参酮IIA胶束的处方优化、表征及其心肌靶向保护作用

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丁伟¹, 张妮¹, 陈韦¹

作者信息

通讯作者:

陈韦

作者简介:

丁伟: 丁伟（1984—），女，副主任医师，硕士，研究方向为中西医结合防治代谢性疾病。E-mail:58810016@qq.com

Optimization, characterization, and evaluation of myocardium-targeting CTP-modified tanshinone II_A micelles for cardioprotection

DING Wei, ZHANG Ni, CHEN Wei

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doi: 10.7501/j.issn.0253-2670.2026.04.008

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摘要

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目的构建并优化一种心肌靶向肽CTP（APWHLSSQYSRT）修饰的丹参酮IIA胶束（cardiac-targeting peptide CTP-modified tanshinone IIA micelles，CTP-Ms/TS IIA），并系统评价其理化特性及体外心肌保护作用。方法采用薄膜水化法制备CTP-Ms/TS IIA，以包封率为核心指标，运用Box-Behnken设计-响应面法（Box-Behnken design-response surface method，BBD-RSM）优化处方参数［聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物（Soluplus）质量浓度、维生素E琥珀酸酯聚乙二醇1000（TPGS₁₀₀₀）质量浓度、水化温度］。利用激光粒度仪和透射电子显微镜（transmission electron microscopy，TEM）表征CTP-Ms/TS IIA的粒径、ζ电位及形貌；以芘为探针测定其临界胶束浓度（critical micelle concentration，CMC），并考察制剂的储藏和血清稳定性。通过荧光显微镜与流式细胞术分析心肌细胞（H9c2）对CTP-Ms/TS IIA的摄取效率，并在异丙肾上腺素诱导的H9c2细胞损伤模型中，采用DCFH-DA和JC-1荧光探针、活死细胞染色及CCK-8检测CTP-Ms/TS IIA对活性氧水平、线粒体功能及细胞存活率的调控作用。结果获得CTP-Ms/TS IIA最佳制备工艺参数：处方体积5 mL，Soluplus质量浓度12 g/L，TPGS₁₀₀₀质量浓度5 g/L，水化温度40 ℃。据此制备的CTP-Ms/TS IIA（膜材含丹参酮IIA、Soluplus、TPGS₁₀₀₀、DSPE-PEG₂₀₀₀、DSPE-PEG₂₀₀₀-CTP），包封率达（90.64±1.01）%（n＝3）。CTP-Ms/TS IIA粒径为（89.30±0.76）nm，ζ电位为（−0.033±0.150）mV；CMC为42.8 mg/L，稳定性良好。与非靶向胶束相比，CTP修饰显著增强了H9c2细胞的摄取效率，并在清除活性氧、恢复线粒体膜电位及改善细胞存活率方面表现出更优效果。结论成功制备了理化性质稳定的CTP-Ms/TS IIA，并通过体外实验验证了其具有心肌靶向与保护潜能；为丹参酮IIA用于心血管疾病防治提供了新的实验基础与潜在的递送方案。

关键词

丹参酮II_A / 心肌细胞靶向 / 靶向药物递送 / Box-Behnken设计-响应面法 / 胶束 / 心肌靶向肽CTP / 临界胶束浓度

Abstract

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Objective To construct and optimize tanshinone II_A (TS II_A)-loaded micelles modified with a cardiomyocyte-targeting peptide CTP (APWHLSSQYSRT) (CTP-Ms/TS II_A), optimize their formulation, and evaluate their physicochemical properties and cardioprotective effects in vitro. Methods CTP-Ms/TS II_A were prepared using the film hydration method. A Box-Behnken response surface design was applied to optimize formulation parameters (Soluplus concentration, TPGS₁₀₀₀ concentration, hydration temperature) with encapsulation efficiency as the evaluation index. Particle size, ζ potential, and morphology of micelles were characterized by dynamic light scattering and transmission electron microscopy (TEM). Critical micelle concentration (CMC) was determined using pyrene as a probe, and storage and serum stability were assessed. Cellular uptake was investigated in H9c2 cardiomyocytes by flow cytometry and fluorescence microscopy. In an isoproterenol-induced H9c2 injury model, intracellular reactive oxygen species (ROS), mitochondrial membrane potential, cell viability, and apoptosis were evaluated by DCFH-DA, JC-1, calcein/PI staining, and CCK-8 assays. Results The optimal preparation parameters were determined as: formulation volume 5 mL, Soluplus concentration 12 g/L, TPGS₁₀₀₀ concentration 5 g/L, and hydration temperature 40 ℃. The CTP-Ms/TS II_A prepared under these conditions (with membrane materials including TS II_A, Soluplus, TPGS₁₀₀₀, DSPE-PEG₂₀₀₀, and DSPE-PEG₂₀₀₀-CTP) achieved a high EE of (90.64 ± 1.01)% (n＝3). The micelles exhibited a particle size of (89.30 ± 0.76) nm, a ζ potential of (−0.033 ± 0.150) mV, and a critical micelle concentration of 42.8 μg/mL, with good stability. Compared with non-targeted micelles, CTP-Ms/TS II_A exhibited significantly enhanced uptake in H9c2 cells, more effective ROS scavenging, restoration of mitochondrial membrane potential, and improved cell survival. Conclusion CTP-Ms/TS II_A with stable physicochemical properties were successfully prepared, and their cardiac-targeting and cardioprotective potential were verified by in vitro experiments. This work provides a new experimental basis and potential delivery strategy for the application of TS II_A in the prevention and treatment of cardiovascular diseases.

Key words

tanshinone II_A / cardiomyocyte targeting / targeted drug delivery / Box-Behnken response surface methodology / micelles / cardiomyocyte-targeting peptide / critical micelle concentration

引用本文

丁伟, 张妮, 陈韦. CTP修饰丹参酮IIA胶束的处方优化、表征及其心肌靶向保护作用. 中草药, 2026 , 57 (4) : 1275 -1285 . DOI: 10.7501/j.issn.0253-2670.2026.04.008

DING Wei, ZHANG Ni, CHEN Wei. Optimization, characterization, and evaluation of myocardium-targeting CTP-modified tanshinone II_A micelles for cardioprotection[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (4) : 1275 -1285 . DOI: 10.7501/j.issn.0253-2670.2026.04.008

基金

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2023年辽宁省科技计划联合计划项目 (2023JH2/101700227); 2022年国家自然科学基金青年基金项目 (82104841)

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2026年第57卷第4期

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doi: 10.7501/j.issn.0253-2670.2026.04.008

接收时间：2025-09-08
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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