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纳米沉淀过程中自传递超分子纳米药物的“反应”式成型

“Reaction”-Like Shaping of Self-Delivery Supramolecular Nanodrugs in the Nanoprecipitation Process

作者:Wenzhe Xu;Yang Chen;Ruixu Yang;Yiying Fu;Wanxin Zhuang;Yonggang Wang;Yi Liu;Hao Zhang;

关键词:nanoprecipitation,self-delivery,nanodrugs,supramolecular interaction,naphthoquinone

DOI:https://doi.org/10.1021/acsnano.3c05229

发表时间:2023年

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摘要

纳米沉淀是通过药物分子在混合溶剂和反溶剂相中的扩散和沉淀来实现的,是构建纳米药物(ND)的经典途径,之前由扩散控制理论指导。然而,在最近制备的自传递超分子ND(SDSND)中,扩散控制机制已经过时了,其特点是在没有载体和表面活性剂的情况下通过超分子相互作用构建药物纳米颗粒。在此,提出了一种由超分子相互作用产生的类似“反应”的补体,用于制备萘醌 SDSND。与扩散控制过程不同,通过类似“反应”的过程,SDSND 的形成速率几乎恒定,并且高度依赖于超分子相互作用决定的分子结合吉布斯自由能。因此,通过设计超分子相互作用,大大提高了SDSND的形成率和药物利用度,这有利于制备具有预期尺寸、成分和治疗功能的SDSND。作为对涉及超分子相互作用的纳米沉淀的深入理解,目前的类似“反应”的方案不仅为经典纳米沉淀提供了理论补充,而且凸显了纳米沉淀在塑造自组装、共组装和金属离子缔合方面的潜力。 SDND。


Abstract

Nanoprecipitation, which is achieved through the diffusion and precipitation of drug molecules in blended solvent and antisolvent phases, is a classic route for constructing nanodrugs (NDs) and previously directed by diffusion-controlled theory. However, the diffusion-controlled mechanism is out of date in the recent preparation of self-delivery supramolecular NDs (SDSNDs), characterized by the construction of drug nanoparticles through supramolecular interactions in the absence of carriers and surfactants. Herein, a “reaction”-like complement, contributed from supramolecular interactions, is proposed for the preparation of naphthoquinone SDSNDs. Different from the diffusion-controlled process, the formation rate of SDSNDs via the “reaction”-like process is almost constant and highly dependent on the supramolecular interaction-determined Gibbs free energy of molecular binding. Thus, the formation rate and drug availability of SDSNDs are greatly improved by engineering the supramolecular interactions, which facilitates the preparation of SDSNDs with expected sizes, components, and therapeutic functions. As a deep understanding of supramolecular-interaction-involved nanoprecipitation, the current “reaction”-like protocol not only provides a theoretical supplement for classic nanoprecipitation but also highlights the potential of nanoprecipitation in shaping self-assembled, coassembled, and metal-ion-associated SDSNDs.