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脂质纳米粒作为药物载体:从概念到临床。

Lipid-based nanoparticles as pharmaceutical drug carriers: from concepts to clinic.

机构信息

Center for Cancer Research Nanobiology Program, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702-1201, USA.

出版信息

Crit Rev Ther Drug Carrier Syst. 2009;26(6):523-80. doi: 10.1615/critrevtherdrugcarriersyst.v26.i6.10.

Abstract

In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nanoemulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles.

摘要

近年来,医学生物学领域的各种纳米技术平台,包括诊断和治疗,受到了极大的关注。此外,在过去十年中,作为药物载体的工程多功能纳米粒子的研究和开发,推动了其在医学领域的应用呈指数级增长。这些纳米粒子的设计原则,包括纳米乳液、树枝状大分子、纳米金、脂质体、药物载体偶联物、抗体-药物复合物和磁性纳米粒子,主要基于合成、天然或生物成分的独特组装,包括但不限于合成聚合物、金属离子、油和脂质作为其构建块。然而,这些粒子在临床上的潜在成功依赖于考虑重要参数,如纳米粒子制造策略、它们的物理性质、药物负载效率、药物释放潜力,以及最重要的是载体本身的最小毒性。在这些方面,基于脂质的纳米粒子具有用于体内应用的毒性最小的优势,并且在使用基于脂质的纳米组装体进行 DNA/RNA 和药物递送方面已经取得了重大进展。在这篇综述中,我们将主要关注基于脂质的纳米粒子在药物递送方面的最新进展和更新。我们从脂质体(所谓的荣誉纳米粒子)领域的当前活动开始回顾,并将详细讨论靶向和触发的挑战性问题。我们将进一步描述来源于一类新型两亲性脂质的纳米粒子,称为双端酰胺两亲物,具有独特的脂质组装特征,最近被用作药物/DNA 递送载体。最后,将介绍一类新兴的新型粒子(基于除磷脂以外的脂质成分),即固体脂质纳米粒和纳米结构脂质载体。我们以目前市售的基于脂质的纳米粒子的一些临床成功制剂为例作为总结。

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