Wu Wenting, Wang Shangdian, Zhou Zhiwei, Guo Zilu, Le Ting, Wu Jun, Xu Chunyan, Wu Xuan
Key Laboratory of Modern Chinese Medicine Preparations Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi 330004, China.
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.
ACS Omega. 2025 Jun 5;10(23):24263-24271. doi: 10.1021/acsomega.4c11475. eCollection 2025 Jun 17.
Bile acid salt (BAS) micellar structures containing phospholipids (PPLs) have many important applications in the field of drug delivery on account of their biocompatibility, but improving their structural stability is a crucial issue for further development. Combined with our previous findings, we hypothesized that coloading of drugs with different hydrophobicities can enhance the structural stability of the micelles. Puerarin (PUE) and tanshinone IIA (TSA) from the Chinese couplet medicines, Radix Puerariae-Salvia miltiorrhiza, were chosen as the model hydrophobic compound pair to be encapsulated into mixed micelles composed of BAS and PPL (BPMM), to form four mixed micellar systems, including blank BPMM, single-drug-carrying BPMM (namely, PUE-loaded BPMM (P-BPMM) and TSA-loaded BPMM (T-BPMM)), and coloaded BPMM (PT-BPMM). The hypothesis was confirmed by comparing the stability of blank BPMM with those of drug-loaded BPMM, single-drug-carrying and drug-cocarrying BPMM, by utilizing molecular dynamics (MD) simulations combined with various experimental observations. Moreover, it is found that the drug distribution preference in the system is not significant when a single drug is loaded. However, when coloaded, the distribution preference of different hydrophobic drugs in the same space is reflected, that is, a more appropriate spatial distribution of drugs in the micellar system can effectively improve the drug-loading stability of the system. The strategy to improve the stability of mixed micelles in this investigation avoids the complex processes associated with modifying the structure of micellar carrier materials and offers the advantages of the use of biosurfactants for drug delivery.
含有磷脂（PPL）的胆汁酸盐（BAS）胶束结构因其生物相容性在药物递送领域有许多重要应用，但提高其结构稳定性是进一步发展的关键问题。结合我们之前的研究结果，我们推测共载不同疏水性的药物可以增强胶束的结构稳定性。选择中药葛根 - 丹参中的葛根素（PUE）和丹参酮IIA（TSA）作为模型疏水化合物对，将其封装到由BAS和PPL组成的混合胶束（BPMM）中，形成四个混合胶束系统，包括空白BPMM、载单药的BPMM（即载PUE的BPMM（P - BPMM）和载TSA的BPMM（T - BPMM））以及共载药的BPMM（PT - BPMM）。通过利用分子动力学（MD）模拟并结合各种实验观察，将空白BPMM的稳定性与载药BPMM、载单药和共载药BPMM的稳定性进行比较，证实了这一假设。此外，发现载单药时系统中的药物分布偏好不明显。然而，当共载药时，反映了不同疏水药物在同一空间的分布偏好，即在胶束系统中药物更合适的空间分布可以有效提高系统的载药稳定性。本研究中提高混合胶束稳定性的策略避免了与修饰胶束载体材料结构相关的复杂过程，并具有使用生物表面活性剂进行药物递送的优势。
