In vivo deposition of poorly soluble drugs,Advanced Drug Delivery Reviews

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In vivo deposition of poorly soluble drugs
Advanced Drug Delivery Reviews ( IF 15.2 ) Pub Date : 2024-06-06 , DOI: 10.1016/j.addr.2024.115358
Zhaohuan Lou ₁ , Chaofeng Mu ₂ , Clairissa D Corpstein ₃ , Tonglei Li ₃

Affiliation

Administered drug molecules, whether dissolved or solubilized, have the potential to precipitate and accumulate as solid forms in tissues and cells within the body. This phase transition can significantly impact the pharmacokinetics of treatment. It is thus crucial to gain an understanding of how drug solubility/permeability, drug formulations and routes of administration affect behaviors of drug deposition. This review examines literature reports on the drug deposition in tissues and cells of poorly water-soluble drugs, as well as underlying physical mechanisms that lead to precipitation. Our work particularly highlights drug deposition in macrophages and the subcellular fate of precipitated drugs. We also propose a tissue permeability-based classification framework to evaluate precipitation potentials of poorly soluble drugs in major organs and tissues. The impact on pharmacokinetics is further discussed and needs to be considered in developing drug delivery systems. Finally, bioimaging techniques that are used to examine aggregated states and the intracellular trafficking of absorbed drugs are summarized.

中文翻译：

难溶性药物的体内沉积

所施用的药物分子，无论是溶解的还是增溶的，都有可能以固体形式沉淀并积聚在体内的组织和细胞中。这种相变可以显着影响治疗的药代动力学。因此，了解药物溶解度/渗透性、药物配方和给药途径如何影响药物沉积行为至关重要。本综述审查了有关难溶于水的药物在组织和细胞中沉积的文献报道，以及导致沉淀的潜在物理机制。我们的工作特别强调巨噬细胞中的药物沉积和沉淀药物的亚细胞命运。我们还提出了一种基于组织渗透性的分类框架来评估难溶性药物在主要器官和组织中的沉淀潜力。对药代动力学的影响需要进一步讨论，并且在开发药物递送系统时需要考虑。最后，总结了用于检查聚集状态和吸收药物的细胞内运输的生物成像技术。

更新日期：2024-06-06

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