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Abstract：
Nanocrystals (NCs) exhibit potential in improving oral bioavailability for poorly water-soluble drugs. However, whether NCs improve oral absorption by quick dissolution or by endocytosis remains inconclusive because tracking of dissolved drugs and NCs particles cannot occur simultaneously. In this study, we aim to elucidate how NCs improve oral absorption by using coumarin 6 (C6), an aggregation-caused quenching fluorophore, and 2-((5-(4-(dip-tolylamino)phenyl)thiophen-2-yl)methylene)malononitrile (MeTTMN), an aggregation-induced emission fluorophore. C6 was used as a model drug to prepare NCs and MeTTMN was incorporated to construct fluorescence resonance energy transfer (FRET) pairs. Thus, the molecular absorption can be detected using the fluorescence signal of dissolved C6 and the NCs particles can be tracked simultaneously by monitoring FRET signals. The reliability of this tracking method was validated. Accordingly, in vitro dissolution, gastrointestinal traffic, and biodistribution studies were conducted. The results showed that dissolved C6 molecules were the main absorption mode of C6 NCs. Identification of such pathways bears considerable significance for the broad application of drug NCs in improving the druggability of insoluble drugs.
摘要：
纳米晶体（NC）在改善水溶性差的药物的口服生物利用度方面具有潜力。然而,NCs是通过快速溶解还是通过内吞作用改善口服吸收仍不确定,因为溶解药物和NCs颗粒的追踪不能同时发生.在这项研究中,我们的目的是阐明NCs如何通过使用香豆素6(C6)来改善口服吸收，聚集引起的猝灭荧光团，和2-((5-(4-(二-甲苯基氨基)苯基)噻吩-2-基)亚甲基)丙二腈(MeTTMN)，聚集诱导的发射荧光团。以C6为模型药物制备NCs,掺入MeTTMN构建荧光共振能量转移(FRET)对。因此，分子吸收可以使用溶解的C6的荧光信号来检测，并且可以通过监测FRET信号来同时跟踪NC颗粒。验证了该跟踪方法的可靠性。因此，体外溶出度,胃肠交通,并进行了生物分布研究。结果表明，溶解的C6分子是C6NC的主要吸收模式。此类途径的鉴定对于药物NC在改善不溶性药物的可成药性方面的广泛应用具有相当重要的意义。
