Evaluation of nanolipoprotein particles (NLPs) as an in vivo delivery platform.
Evaluation of nanolipoprotein particles (NLPs) as an in vivo delivery platform.
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评估纳米脂蛋白颗粒（NLP）作为体内递送平台。
DOI：
10.1371/journal.pone.0093342
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Blanchette CD
中科院分区：
文献类型：
--
作者：
Fischer NO;Weilhammer DR;Dunkle A;Thomas C;Hwang M;Corzett M;Lychak C;Mayer W;Urbin S;Collette N;Chiun Chang J;Loots GG;Rasley A;Blanchette CD
纳米颗粒在治疗药物的递送方面前景广阔，但在使用这些纳米系统有效、持久地靶向递送治疗药物方面仍然存在局限性，包括赋予平台功能、体内稳定性、药物包封效率和毒性。为了开始解决这些限制，我们评估了纳米脂蛋白颗粒（NLP）的功能性、稳定性、细胞毒性、毒性、免疫原性和体内生物分布，纳米脂蛋白颗粒（NLP）是天然存在的高密度脂蛋白（HDL）的模拟物。我们发现，许多分子都可以可靠地与NLP结合，包括蛋白质、单链DNA和小分子。还发现NLP在复杂的生物液体中相对稳定，并且在高达320 µg/ml的剂量下在体外没有显示出细胞毒性。此外，我们观察到连续14天每天体内施用NLP不会引起显著的体重减轻或导致切除器官的病变。此外，NLP在抗体生成方面未显示明显的免疫原性。最后，发现NLP在体内的生物分布高度依赖于给药途径，其中鼻内给药导致在肺组织中的滞留时间延长。尽管仅评估了选定数量的NLP组合物，但本研究的结果表明，NLP平台有望用作一系列治疗剂的靶向和非靶向体内递送载体。
Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. To begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP was also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Although only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics.
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