Agarwal Rachit, Roy Krishnendu
Department of Biomedical Engineering, The University of Texas, Austin, TX 78712, USA.
Ther Deliv. 2013 Jun;4(6):705-23. doi: 10.4155/tde.13.37.
Recent progress in drug discovery has enabled the targeting of specific intracellular molecules to achieve therapeutic effects. These next-generation therapeutics are often biologics that cannot enter cells by mere diffusion. Therefore, it is imperative that drug carriers are efficiently internalized by cells and reach specific target organelles before releasing their cargo. Nanoscale polymeric carriers are particularly suitable for such intracellular delivery. Although size and surface charge have been the most studied parameters for nanocarriers, it is now well appreciated that other properties, for example, particle shape, elasticity and surface composition, also play a critical role in their transport across physiological barriers. It is proposed that a multivariate design space that considers the interdependence of particle geometry with its mechanical and surface properties must be optimized to formulate drug nanocarriers for effective accumulation at target sites and efficient intracellular delivery.
药物研发的最新进展使得针对特定细胞内分子以实现治疗效果成为可能。这些新一代治疗药物通常是生物制剂，无法通过单纯扩散进入细胞。因此，药物载体必须被细胞有效地内化，并在释放其负载之前到达特定的靶细胞器。纳米级聚合物载体特别适合这种细胞内递送。尽管尺寸和表面电荷一直是纳米载体研究最多的参数，但现在人们充分认识到，其他性质，例如颗粒形状、弹性和表面组成，在其跨越生理屏障的运输中也起着关键作用。有人提出，必须优化一个多变量设计空间，该空间考虑颗粒几何形状与其机械和表面性质的相互依存关系，以制备药物纳米载体，使其在靶部位有效积累并实现高效的细胞内递送。
