UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials Group, Avenue Emmanuel Mounier 73, 1200 Brussels, Belgium.
UCLouvain, Université catholique de Louvain, Institute of Experimental and Clinical Research, Laboratory of Hepato-Gastroenterology, Avenue Emmanuel Mounier 53, 1200 Brussels, Belgium.
J Control Release. 2023 Nov;363:415-434. doi: 10.1016/j.jconrel.2023.09.040. Epub 2023 Oct 1.
Nonalcoholic fatty liver disease (NAFLD) affects approximately 25% of the adult population worldwide. This pathology can progress into end-stage liver disease with life-threatening complications, and yet no pharmacologic therapy has been approved. NAFLD is commonly characterized by excessive fat accumulation in the liver and is in closely associated with insulin resistance and metabolic disorders, which suggests that NAFLD is the hepatic manifestation of metabolic syndrome. Regarding treatment options, the current validated strategy relies on lifestyle modifications (exercise and diet restrictions). Although there are no approved drug-based treatments, several clinical trials are ongoing. Novel targets are being discovered, and the repurposing of drugs that show promising effects in NAFLD is starting to gain more interest. The field of nanotechnology has been growing at an increasing rate, with new and more efficient drug delivery strategies being developed for NAFLD treatment. Nanocarriers can easily encapsulate drugs that need to be better protected from the organism to exert their effect or that need help at reaching their target, thereby helping achieve a better bioavailability. Drug delivery systems can also be designed to target the site of the disease, in this case, the liver. In this review, we focus on the current knowledge of NAFLD pathology, the targets being considered for clinical trials, and the current guidelines and ongoing clinical trials, with a specific focus on potential oral treatments for NAFLD using promising drug delivery strategies.
非酒精性脂肪性肝病（NAFLD）影响全球约 25%的成年人。这种病理可进展为危及生命的并发症的终末期肝病，但尚无批准的药物治疗。NAFLD 通常的特征是肝脏中脂肪过度积累，与胰岛素抵抗和代谢紊乱密切相关，这表明 NAFLD 是代谢综合征的肝脏表现。关于治疗选择，目前经证实的策略依赖于生活方式的改变（运动和饮食限制）。尽管没有批准的基于药物的治疗方法，但正在进行几项临床试验。新的靶点正在被发现，并且重新利用在 NAFLD 中显示出有希望效果的药物开始引起更多关注。纳米技术领域的发展速度正在加快，为 NAFLD 治疗开发了新的、更有效的药物输送策略。纳米载体可以轻松地封装需要更好地保护免受机体影响以发挥作用或需要帮助才能到达其靶标的药物，从而有助于实现更好的生物利用度。药物输送系统也可以设计为针对疾病部位，在这种情况下，是肝脏。在这篇综述中，我们重点介绍了 NAFLD 病理学的现有知识、正在考虑用于临床试验的靶点以及当前的指南和正在进行的临床试验，特别关注使用有前途的药物输送策略治疗 NAFLD 的潜在口服治疗方法。
