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目前临床中的纳米医学真正形成了纳米颗粒吗?

What nanomedicine in the clinic right now really forms nanoparticles?

机构信息

Drug Delivery Solutions LLC, Arlington, MA, USA.

出版信息

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2014 Mar-Apr;6(2):125-35. doi: 10.1002/wnan.1257. Epub 2014 Jan 10.


DOI:10.1002/wnan.1257
PMID:24415653
Abstract

Some researchers believe nanomedicine will revolutionize healthcare and medicine through transformative new therapeutic tools. Nanocarriers, utilized to transport actives to the target site, are constructed from a wide range of materials. Nanocarriers can be grouped into self-assembling (liposomes, micelles), processed (nanoparticles, emulsions), and chemically bound (dendrimers, silica-based carriers, carbon nanotubes) structures. A review of nanomedicines on the market and in clinical translation reveals that the vast majority is based on liposomes, polymeric micelles, and nanoparticles. The increasing presence of these novel nanomedicines raises the question what nanomedicines in the clinic right now really form nanoparticles, i.e., are improvements we see from nanomedicines structure-related or do they result from improved formulations? Do we even have sufficient data to address this question? The formation of nanocarriers is usually confirmed in vitro but little if any in vivo (let alone clinical) information is available. Given the large number of nanomedicines on the market and under clinical evaluation one clearly cannot expect to find a 'one size fits all' answer. Therefore, two case studies are discussed: the paclitaxel formulation Taxol® and its nanomedicine companions LEP-ETU (liposome), Genexol®-PM and NK105 (micelles), and Abraxane® (nanoparticle). Published pharmacokinetic data is utilized to find differences indicating nanocarrier delivery. The second case study involves structurally related camptothecin-polymer conjugates CRLX101 (nanoparticles) and XMT-1001 (prodrug). Structural differences are evaluated to discuss the different aggregation behavior. This opinion can only serve as first attempt to find a more general answer; clearly more data is needed from future studies.

摘要

一些研究人员认为,通过变革性的新型治疗工具,纳米医学将彻底改变医疗保健和医学领域。纳米载体被用于将活性剂递送到靶位,它们由各种材料构建而成。纳米载体可分为自组装(脂质体、胶束)、加工(纳米颗粒、乳液)和化学结合(树枝状大分子、基于硅的载体、碳纳米管)结构。对市场上和临床转化中的纳米药物的综述表明,绝大多数基于脂质体、聚合物胶束和纳米颗粒。这些新型纳米药物的日益普及引发了一个问题,即目前临床中真正形成纳米颗粒的纳米药物有哪些,也就是说,我们从纳米药物的结构相关方面看到的改进,还是因为改进了配方?我们是否有足够的数据来回答这个问题?纳米载体的形成通常在体外得到证实,但体内(更不用说临床)信息很少。鉴于市场上和正在临床评估中的纳米药物数量众多,显然不能期望找到一个“一刀切”的答案。因此,讨论了两个案例研究:紫杉醇制剂 Taxol®及其纳米药物同伴 LEP-ETU(脂质体)、Genexol®-PM 和 NK105(胶束)和 Abraxane®(纳米颗粒)。利用已发表的药代动力学数据来寻找表明纳米载体递送的差异。第二个案例研究涉及结构相关的喜树碱-聚合物缀合物 CRLX101(纳米颗粒)和 XMT-1001(前药)。评估结构差异以讨论不同的聚集行为。本观点仅可作为寻找更普遍答案的初步尝试;显然,未来研究需要更多数据。

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