Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
J Control Release. 2023 Nov;363:507-524. doi: 10.1016/j.jconrel.2023.10.002. Epub 2023 Oct 9.
Many viruses, bacteria, and parasites rely on the lymphatic system for survival, replication, and dissemination. While conventional anti-infectives can combat infection-causing agents in the bloodstream, they do not reach the lymphatic system to eradicate the pathogens harboured there. This can result in ineffective drug exposure and reduce treatment effectiveness. By developing effective lymphatic delivery strategies for antiviral, antibacterial, and antiparasitic drugs, their systemic pharmacokinetics may be improved, as would their ability to reach their target pathogens within the lymphatics, thereby improving clinical outcomes in a variety of acute and chronic infections with lymphatic involvement (e.g., acquired immunodeficiency syndrome, tuberculosis, and filariasis). Here, we discuss approaches to targeting anti-infective drugs to the intestinal and dermal lymphatics, aiming to eliminate pathogen reservoirs and interfere with their survival and reproduction inside the lymphatic system. These include optimized lipophilic prodrugs and drug delivery systems that promote lymphatic transport after oral and dermal drug intake. For intestinal lymphatic delivery via the chylomicron pathway, molecules should have logP values >5 and long-chain triglyceride solubilities >50 mg/g, and for dermal lymphatic delivery via interstitial lymphatic drainage, nanoparticle formulations with particle size between 10 and 100 nm are generally preferred. Insight from this review may promote new and improved therapeutic solutions for pathogen eradication and combating infective diseases, as lymphatic system involvement in pathogen dissemination and drug resistance has been neglected compared to other pathways leading to treatment failure.
许多病毒、细菌和寄生虫依赖淋巴系统生存、复制和传播。虽然传统的抗感染药物可以对抗血液中的感染因子，但它们无法到达淋巴系统来消灭那里的病原体。这可能导致药物暴露不足，降低治疗效果。通过为抗病毒、抗菌和抗寄生虫药物开发有效的淋巴递药策略，可以改善其全身药代动力学特性，以及在淋巴系统内到达目标病原体的能力，从而改善各种涉及淋巴系统的急性和慢性感染的临床结局（例如，获得性免疫缺陷综合征、结核病和丝虫病）。在这里，我们讨论了将抗感染药物靶向肠道和皮肤淋巴系统的方法，旨在消除病原体储存库并干扰其在淋巴系统内的生存和繁殖。这些方法包括优化亲脂性前药和药物递送系统，以促进口服和皮肤药物摄入后的淋巴转运。对于通过乳糜微粒途径的肠道淋巴递药，分子的 logP 值应>5，长链甘油三酯溶解度应>50mg/g，而对于通过间质淋巴引流的皮肤淋巴递药，粒径在 10 至 100nm 之间的纳米粒制剂通常是优选的。本综述中的见解可能会促进新的和改进的治疗方法来根除病原体和对抗传染病，因为与导致治疗失败的其他途径相比，淋巴系统在病原体传播和耐药性方面的作用被忽视了。
