Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Chem Soc Rev. 2012 Apr 7;41(7):2971-3010. doi: 10.1039/c2cs15344k. Epub 2012 Mar 5.
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).
聚合物材料在医药和生物技术产品中已经使用了超过 40 年。这些材料已经从早期的可生物降解产品发展而来，如可吸收缝线、骨科植入物、宏观和微观药物传递系统，如用作控制药物释放储库的微球和薄片，发展到能够靶向和控制治疗和诊断剂释放的多功能纳米颗粒（NPs）。这些新一代的靶向和控制释放聚合物 NPs 现在被设计成能够在复杂的体内环境中导航，并整合实现靶向特异性、控制药物浓度和组织、细胞和亚细胞水平药物暴露动力学的功能。事实上，这种通过精心设计多功能 NPs 来优化药物药理学可以提高药物安全性和疗效，并且可以与传统上通过药物化学实现的药物增强互补。在这方面，聚合物 NPs 有可能产生一种高度差异化的新型治疗药物，与它们组成的原始活性药物不同，也与主要促进药物配方的第一代 NPs 不同。在将药物分子本身纳入 NPs 后，药物分子本身的设计也可能更加灵活，因为药物特性（溶解度、代谢、血浆结合、生物分布、靶组织积累）将不再受到药物化学成分的同样限制，而且还将部分成为 NP 的物理化学性质的功能。最佳设计的药物与最佳设计的聚合物 NPs 的结合，为改善临床结果提供了可能性，而这些结果可能无法通过常规形式的药物给药来实现。在这篇重要的综述中，我们旨在深入了解靶向聚合物 NPs 的设计和开发，并强调与这种新型治疗药物工程相关的挑战，包括 NP 设计优化、开发和生物物理化学性质的考虑。此外，我们还强调了文献中的一些最新实例，展示了靶向聚合物 NPs 在设计和应用方面的当前趋势和新观念（444 篇参考文献）。
