ACS Appl Mater Interfaces. 2018 Sep 26;10(38):31870-31881. doi: 10.1021/acsami.8b09069. Epub 2018 Sep 13.
The use of nanocarriers to deliver poorly soluble drugs to the sites of diseases is an attractive and general method, and mesoporous silica nanoparticles (MSNs) are increasingly being used as carriers. However, both loading a large amount of drugs into the pores and still being able to release the drug is a challenge. In this paper, we demonstrate a general strategy based on a companion molecule that chaperones the drug into the pores and also aids it in escaping. A common related strategy is to use a miscible co-solvent dimethyl sulfoxide (DMSO), but although loading may be efficient in DMSO, this co-solvent frequently diffuses into an aqueous environment, leaving the drug behind. We demonstrate the method by using acetophenone (AP), an FDA-approved food additive as the chaperone for clofazimine (CFZ), a water-insoluble antibiotic used to treat leprosy and multidrug-resistant tuberculosis. AP enables a high amount of CFZ cargo into the MSNs and also carries CFZ cargo out from the MSNs effectively when they are in an aqueous biorelevant environment. The amount of loading and the CFZ release efficiency from MSNs were optimized; 4.5 times more CFZ was loaded in MSNs with AP than that with DMSO and 2300 times more CFZ was released than that without the assistance of the AP. In vitro treatment of macrophages infected by Mycobacterium tuberculosis with the optimized CFZ-loaded MSNs killed the bacteria in the cells in a dose-dependent manner. These studies demonstrate a highly efficient method for loading nanoparticles with water-insoluble drug molecules and the efficacy of the nanoparticles in delivering drugs into eukaryotic cells in aqueous media.
利用纳米载体将难溶性药物递送到疾病部位是一种有吸引力和通用的方法，介孔硅纳米粒子（MSNs）越来越多地被用作载体。然而，将大量药物载入孔中并仍然能够释放药物是一个挑战。在本文中，我们展示了一种基于伴侣分子的通用策略，该策略可以引导药物进入孔中并帮助其逃逸。一种常见的相关策略是使用可混溶的共溶剂二甲基亚砜（DMSO），但尽管在 DMSO 中载药可能有效，但这种共溶剂经常扩散到水相环境中，将药物留在后面。我们通过使用苯乙酮（AP）作为氯法齐明（CFZ）的伴侣分子来证明该方法，AP 是一种 FDA 批准的食品添加剂，用于治疗麻风病和耐多药结核病。AP 能够将大量 CFZ 货物载入 MSNs 中，并且当它们处于水相生物相关环境中时，也能够有效地将 CFZ 货物从 MSNs 中带出。优化了载药量和 MSNs 中 CFZ 的释放效率；与 DMSO 相比，AP 载入 MSNs 的 CFZ 量增加了 4.5 倍，而没有 AP 协助的 CFZ 释放量增加了 2300 倍。用优化的载有 CFZ 的 MSNs 处理感染结核分枝杆菌的巨噬细胞，以剂量依赖的方式杀死细胞内的细菌。这些研究证明了一种将纳米粒子负载入水不溶性药物分子的高效方法，以及纳米粒子在水相介质中将药物递送到真核细胞中的功效。
