Bhattacharjee Sourav, Brayden David J
School of Veterinary Medicine, University College Dublin (UCD), Belfield, Dublin, Ireland.
Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD), Belfield, Dublin, Ireland.
Expert Opin Drug Discov. 2021 Mar;16(3):235-254. doi: 10.1080/17460441.2021.1826434. Epub 2020 Oct 27.
Nanotechnology is in a growth phase for drug delivery and medical imaging. Nanomaterials with unique properties present opportunities for encapsulation of therapeutics and imaging agents, along with conjugation to ligands for targeting. Favorable chemistry of nanomaterials can create formulations that address critical challenges for therapeutics, such as insolubility and a low capacity to cross the blood-brain-barrier (BBB) and intestinal wall.
The authors investigate challenges faced during translation of nanomedicines while suggesting reasons as to why some nanoformulations have under-performed in clinical trials. They assess physiological barriers such as the BBB and gut mucus that nanomedicines must overcome to deliver cargos. They also provide an overview with examples of how nanomedicines can be designed to improve localization and site-specific delivery (e.g., encapsulation, bioconjugation, and triggered-release).
There are examples where nanomedicines have demonstrated improved efficacy of payload in humans; however, most of the advantages conferred were in improved pharmacokinetics and reduced toxicity. Problematic data show susceptibility of nanoformulations against natural protective mechanisms present in the body, including distribution impediment by physiological barriers and activation of the reticuloendothelial system. Further initiatives should address current challenges while expanding the scope of nanomedicine into advanced biomedical imaging and antibiotic delivery.
纳米技术正处于药物递送和医学成像的发展阶段。具有独特性质的纳米材料为治疗药物和成像剂的封装以及与靶向配体的缀合提供了机会。纳米材料良好的化学性质可以创造出能够应对治疗关键挑战的制剂,如不溶性以及穿越血脑屏障(BBB)和肠壁的能力较低。
作者研究了纳米药物转化过程中面临的挑战,同时指出了一些纳米制剂在临床试验中表现不佳的原因。他们评估了纳米药物为递送货物必须克服的生理屏障,如血脑屏障和肠道黏液。他们还通过实例概述了如何设计纳米药物以改善定位和位点特异性递送(例如封装、生物缀合和触发释放)。
有实例表明纳米药物在人体中提高了有效载荷的疗效;然而,所带来的大多数优势在于改善了药代动力学和降低了毒性。有问题的数据显示纳米制剂对体内天然保护机制敏感,包括生理屏障造成的分布阻碍和网状内皮系统的激活。未来的举措应解决当前的挑战,同时将纳米医学的范围扩展到先进的生物医学成像和抗生素递送领域。