Targeted polymeric therapeutic nanoparticles: design, development and clinical translation.
Targeted polymeric therapeutic nanoparticles: design, development and clinical translation.
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DOI：
10.1039/c2cs15344k
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发表时间：
2012-04-07
影响因子：
46.2
通讯作者：
Farokhzad OC
中科院分区：
文献类型：
--
作者：
Kamaly N;Xiao Z;Valencia PM;Radovic-Moreno AF;Farokhzad OC
聚合物材料已用于一系列制药和生物技术产品超过40年。这些材料已经从其早期用作生物可降解产品（如可吸收缝合线、骨科植入物、宏观和微观药物递送系统（如用作药物控释库的微粒和薄片））发展到能够靶向和控释治疗剂和诊断剂的多功能纳米颗粒（NP）。这些新一代的靶向和控释聚合物NP现在被工程化以在复杂的体内环境中导航，并结合用于在组织、细胞和亚细胞水平上实现靶特异性、药物浓度控制和暴露动力学的功能。事实上，通过仔细设计多功能NP来辅助药物药理学的这种优化可以改善药物安全性和有效性，并且可以补充传统上通过药物化学实现的药物增强。在这方面，聚合物NP具有产生高度分化的新型治疗剂的潜力，其不同于在其组合物中使用的原始活性药物，并且不同于在很大程度上促进药物制剂的第一代NP。药物分子本身设计的更大灵活性也可以在它们并入NP后得到促进，因为药物性质（溶解度、代谢、血浆结合、生物分布、靶组织积累）将不再受药物化学组成的相同程度的限制，而是部分地成为NP的物理化学性质的功能。最佳设计的药物与最佳工程化的聚合物NP的组合开辟了改善临床结果的可能性，这可能是以其常规形式施用药物无法实现的。在这篇重要的综述中，我们的目标是提供对靶向聚合物纳米颗粒的设计和开发的见解，并强调与这类新型治疗药物的工程相关的挑战，包括对纳米颗粒设计优化，开发和生物制药化学特性的考虑。此外，我们强调了一些最近的例子，从文献中，这表明目前的趋势和新概念的设计和实用性的目标聚合物纳米粒子（444参考文献）。
Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
14
作者：
Balthasar, S;Michaelis, K;Langer, K
通讯作者：
Langer, K
DOI：
10.1073/pnas.241655998
发表时间：
2002-02-05
影响因子：
11.1
作者：
Arap, W;Haedicke, W;Ruoslahti, E
通讯作者：
Ruoslahti, E
影响因子：
16.1
作者：
Aggarwal P;Hall JB;McLeland CB;Dobrovolskaia MA;McNeil SE
通讯作者：
McNeil SE
影响因子：
5.6
作者：
BANGHAM, AD;STANDISH, MM;WATKINS, JC
通讯作者：
WATKINS, JC