癌症纳米药物:论文多,药物少!
Cancer nanomedicines: so many papers and so few drugs!
机构信息
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, 94143-0912, USA.
出版信息
Adv Drug Deliv Rev. 2013 Jan;65(1):80-8. doi: 10.1016/j.addr.2012.09.038. Epub 2012 Oct 1.
This review identifies a timeline to nanomedicine anticancer drug approval using the business model of inventors, innovators and imitators. By evaluating the publication record of nanomedicine cancer therapeutics we identified a trend of very few publications prior to FDA approval. We first enumerated the publications related to cancer involving polymers, liposomes or monoclonal antibodies and determined the number of citations per publication as well as the number of published clinical trials among the publications. Combining these data with the development of specific nanomedicines, we are able to identify an invention phase consisting of seminal papers in basic science necessary for the development of a specific nanomedicine. The innovation phase includes the first report, the development and the clinical trials involving that nanomedicine. Finally, the imitation phase begins after approval when others ride the wave of success by using the same formulation for new drugs or using the same drug to validate other nanomedicines. We then focused our analysis on nanomedicines containing camptothecin derivatives, which are not yet approved including two polymers considered innovations and one liposomal formulation in the imitation phase. The conclusion that may be drawn from the analysis of the camptothecins is that approved drugs reformulated in polymeric and liposomal cancer nanomedicines have a more difficult time navigating through the approval process than the parent molecule. This is probably due to the fact that for most currently approved drugs, reformulating them in a nanocarrier provides a small increase in performance that large pharmaceutical companies do not consider being worth the time, effort and expense of development. It also appears that drug carriers have a more difficult path through the clinic than monoclonal antibodies. The added complexity of nanocarriers also deters their use to deliver new molecular entities. Thus, the new drug candidates that might be most improved by drug delivery in nanocarriers are not formulated in this fashion.
这篇综述确定了纳米医学抗癌药物批准的时间线,使用的是发明者、创新者和模仿者的商业模式。通过评估纳米医学癌症疗法的发表记录,我们发现,在 FDA 批准之前,相关出版物非常少。我们首先列举了涉及聚合物、脂质体或单克隆抗体的癌症相关出版物,并确定了每篇出版物的引用数量以及出版物中已发表临床试验的数量。将这些数据与特定纳米药物的开发相结合,我们能够确定一个发明阶段,该阶段包括特定纳米药物开发所必需的基础科学的开创性论文。创新阶段包括第一个报告、该纳米药物的开发和临床试验。最后,在获得批准后,模仿阶段开始,其他人通过使用相同的制剂用于新药或使用相同的药物来验证其他纳米药物来跟风成功。然后,我们将分析重点放在含有喜树碱衍生物的纳米药物上,这些药物尚未获得批准,包括两种被认为是创新的聚合物和一种处于模仿阶段的脂质体配方。从喜树碱的分析中可以得出的结论是,在聚合物和脂质体癌症纳米药物中重新配方的已批准药物在通过批准过程方面比母体分子更具挑战性。这可能是因为对于大多数目前批准的药物,将它们重新配方成纳米载体只会在性能上略有提高,而大型制药公司认为这不值得花费时间、精力和费用来进行开发。看起来药物载体在临床试验中也比单克隆抗体更具挑战性。纳米载体的复杂性增加也阻碍了它们用于输送新的分子实体。因此,通过纳米载体进行药物输送最有可能改善的新药候选物并没有以这种方式进行配方。