纳米颗粒介导的药物传递系统治疗炎症性肠病:当前的观点。

Nanoparticle-Mediated Drug Delivery Systems For The Treatment Of IBD: Current Perspectives.

机构信息

Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA.

Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA.

出版信息

Int J Nanomedicine. 2019 Nov 13;14:8875-8889. doi: 10.2147/IJN.S210315. eCollection 2019.

Abstract

Inflammatory bowel disease (IBD), which mainly consists of Crohn's disease and ulcerative colitis, is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The traditional treatment strategies relied on frequent administration of high dosages of medications, including antibiotics, non-steroidal anti-inflammatory drugs, biologics, and immunomodulators, with the goal of reducing inflammation. Some of these medications were effective in alleviating the early-stage inflammatory symptoms, but their long-term efficacies were compromised by the accumulation of toxicities. Recently, nanoparticle (NP)-based drugs have been widely studied for their potential to solve such problems. Various mechanisms/strategies, including size-, charge-, pH-, pressure-, degradation-, ligand-receptor-, and microbiome- dependent drug delivery systems, have been exploited in preclinical studies. A certain number of NP delivery systems have sought to target drugs to the inflamed intestine. Although several NP-based drugs have entered clinical trials for the treatment of IBD, most have failed due to premature drug release, weak targeting ability, and the high immune toxicity of some of the synthetic nanomaterials that have been used to fabricate the NPs. Therefore, there is still a need for rationally designed and stable NP drug delivery system that can specifically target drugs to the disease site, prolong the drug's residence time, and minimize systemic side effects. This review will analyze the current state of the art in NP-mediated drug delivery for IBD treatment. We will focus on topics such as deliverable targets (at the tissue or cellular level) for treating inflammation; the target-homing NP materials that can interact with such targets; and the major administration routes for treating IBD. These discussions will integrate notable trends in the research and development of IBD medications, including multi-responsive NP-mediated delivery and naturally-derived targeting NPs. Finally, current challenges and future directions will be presented in the hopes of advancing the study of NP-mediated strategies for treating IBD.

摘要

炎症性肠病(IBD)主要包括克罗恩病和溃疡性结肠炎,是一种慢性和复发性胃肠道炎症性疾病。传统的治疗策略依赖于频繁给予高剂量的药物,包括抗生素、非甾体抗炎药、生物制剂和免疫调节剂,以减轻炎症。这些药物中的一些在缓解早期炎症症状方面有效,但由于毒性的积累,其长期疗效受到影响。最近,纳米颗粒(NP)药物因其潜在的解决这些问题的能力而被广泛研究。在临床前研究中,已经利用了各种机制/策略,包括大小、电荷、pH 值、压力、降解、配体-受体和微生物组依赖的药物传递系统。一些 NP 给药系统试图将药物靶向到发炎的肠道。尽管有几种 NP 药物已进入治疗 IBD 的临床试验,但由于过早释放药物、靶向能力弱以及用于制造 NPs 的一些合成纳米材料的高免疫毒性,大多数药物都失败了。因此,仍然需要设计合理且稳定的 NP 药物传递系统,该系统能够将药物特异性靶向到疾病部位,延长药物的驻留时间,并最小化全身副作用。本综述将分析用于治疗 IBD 的 NP 介导药物传递的最新进展。我们将重点关注可用于治疗炎症的可传递的靶点(在组织或细胞水平上)、可与这些靶点相互作用的靶向 NP 材料以及用于治疗 IBD 的主要给药途径等主题。这些讨论将整合 IBD 药物研发中的显著趋势,包括多响应性 NP 介导的传递和天然靶向 NP。最后,将提出当前的挑战和未来的方向,希望能推进 NP 介导的治疗 IBD 策略的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0847/6859086/9c877333e29b/IJN-14-8875-g0001.jpg

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