Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
J Colloid Interface Sci. 2024 Sep;669:731-739. doi: 10.1016/j.jcis.2024.05.029. Epub 2024 May 8.
Hydrophilic cationic drugs such as mitoxantrone hydrochloride (MTO) pose a significant delivery challenge to the development of nanodrug systems. Herein, we report the use of a hydrophobic ion-pairing strategy to enhance the nano-assembly of MTO.
We employed biocompatible sodium cholesteryl sulfate (SCS) as a modification module to form stable ion pairs with MTO, which balanced the intermolecular forces and facilitated nano-assembly. PEGylated MTO-SCS nanoassemblies (pMS NAs) were prepared via nanoprecipitation. We systematically evaluated the effect of the ratio of the drug module (MTO) to the modification module (SCS) on the nanoassemblies.
The increased lipophilicity of MTO-SCS ion pair could significantly improve the encapsulation efficiency (∼97 %) and cellular uptake efficiency of MTO. The pMS NAs showed prolonged blood circulation, maintained the same level of tumor antiproliferative activity, and exhibited reduced toxicity compared with the free MTO solution. It is noteworthy that the stability, cellular uptake, cytotoxicity, and in vivo pharmacokinetic behavior of the pMS NAs increased in proportion to the molar ratio of SCS to MTO. This study presents a self-assembly strategy mediated by ion pairing to overcome the challenges commonly associated with the poor assembly ability of hydrophilic cationic drugs.
盐酸米托蒽醌（MTO）等亲水性阳离子药物对纳米药物系统的发展构成了重大的递药挑战。在此，我们报告了使用疏水性离子对策略来增强 MTO 的纳米组装。
我们采用生物相容性的胆甾醇硫酸钠（SCS）作为修饰模块，与 MTO 形成稳定的离子对，平衡分子间力，促进纳米组装。通过纳米沉淀法制备了 PEG 化 MTO-SCS 纳米组装体（pMS NAs）。我们系统地评估了药物模块（MTO）与修饰模块（SCS）的比例对纳米组装体的影响。
MTO-SCS 离子对的亲脂性增加可显著提高 MTO 的包封效率（约 97%）和细胞摄取效率。pMS NAs 表现出延长的血液循环，保持与游离 MTO 溶液相同水平的肿瘤抗增殖活性，并且表现出降低的毒性。值得注意的是，pMS NAs 的稳定性、细胞摄取、细胞毒性以及体内药代动力学行为与 SCS 与 MTO 的摩尔比成正比增加。本研究提出了一种由离子配对介导的自组装策略，以克服亲水性阳离子药物组装能力差的常见挑战。
