Puccetti Matteo, Pariano Marilena, Wojtylo Paulina, Schoubben Aurélie, Giovagnoli Stefano, Ricci Maurizio
Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy.
Department of Medicine, University of Perugia, 06132 Perugia, Italy.
Pharmaceutics. 2023 Feb 3;15(2):506. doi: 10.3390/pharmaceutics15020506.
Developing therapeutics for inflammatory diseases is challenging due to physiological mucosal barriers, systemic side effects, and the local microbiota. In the search for novel methods to overcome some of these problems, drug delivery systems that improve tissue-targeted drug delivery and modulate the microbiota are highly desirable. Microbial metabolites are known to regulate immune responses, an observation that has resulted in important conceptual advances in areas such as metabolite pharmacology and metabolite therapeutics. Indeed, the doctrine of "one molecule, one target, one disease" that has dominated the pharmaceutical industry in the 20th century is being replaced by developing therapeutics which simultaneously manipulate multiple targets through novel formulation approaches, including the multitarget-directed ligands. Thus, metabolites may not only represent biomarkers for disease development, but also, being causally linked to human diseases, an unexploited source of therapeutics. We have shown the successful exploitation of this approach: by deciphering how signaling molecules, such as the microbial metabolite, indole-3-aldehyde, and the repurposed drug anakinra, interact with the aryl hydrocarbon receptor may pave the way for novel therapeutics in inflammatory human diseases, for the realization of which drug delivery platforms are instrumental.
由于生理黏膜屏障、全身副作用和局部微生物群的存在，开发针对炎症性疾病的治疗方法具有挑战性。在寻找克服其中一些问题的新方法时，能够改善组织靶向药物递送并调节微生物群的药物递送系统非常值得期待。已知微生物代谢产物可调节免疫反应，这一发现已在代谢产物药理学和代谢产物治疗学等领域带来了重要的概念性进展。事实上，20世纪主导制药行业的“一种分子、一个靶点、一种疾病”的理念正被通过新型制剂方法同时操纵多个靶点的治疗方法所取代，包括多靶点导向配体。因此，代谢产物不仅可能代表疾病发展的生物标志物，而且作为与人类疾病有因果关系的物质，还是一种未被开发的治疗来源。我们已经证明了这种方法的成功应用：通过解读信号分子，如微生物代谢产物吲哚-3-醛和重新利用的药物阿那白滞素，如何与芳烃受体相互作用，可能为炎症性人类疾病的新型治疗方法铺平道路，而药物递送平台对于实现这一目标至关重要。
