The effect of particle size on the biodistribution of low-modulus hydrogel PRINT particles.
The effect of particle size on the biodistribution of low-modulus hydrogel PRINT particles.
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DOI：
10.1016/j.jconrel.2012.06.009
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发表时间：
2012-08-20
期刊：
影响因子：
--
通讯作者：
DeSimone JM
中科院分区：
文献类型：
--
作者：
Merkel TJ;Chen K;Jones SW;Pandya AA;Tian S;Napier ME;Zamboni WE;DeSimone JM
越来越多的人认识到，用于药物输送的颗粒的可变形性在其生物分布和循环剖面中起着重要作用。了解这些效应将为合理设计给药系统提供重要工具。虽然在大小、形状和可变形性上与红细胞相似的颗粒与刚性但其他方面相似的颗粒相比，延长了循环时间并改变了生物分布曲线，但这种高度可变形的大小不同的颗粒的体内行为尚未被探索。我们报道了一系列圆盘状、单分散、低模量的水凝胶颗粒的制备，其直径从0.8到8.9 μm不等，尺寸小于或大于红细胞。我们将这些颗粒注射到健康小鼠体内，并追踪它们在血液中的浓度以及它们在主要器官中的分布。这些可变形的颗粒在肺和脾等过滤组织中都表现出一定的滞留，然后释放回循环中，其特征是这些组织中的颗粒减少，同时血液中的颗粒浓度增加。大小与红细胞相似的颗粒显示出更长的循环时间，这表明这种大小和形状的可变形颗粒非常适合避免清除。
There is a growing recognition that the deformability of particles used for drug delivery plays a significant role on their biodistribution and circulation profile. Understanding these effects would provide a crucial tool for the rational design of drug delivery systems. While particles resembling red blood cells (RBCs) in size, shape and deformability have extended circulation times and altered biodistribution profiles compared to rigid, but otherwise similar particles, the in vivo behavior of such highly deformable particles of varied size has not been explored. We report the fabrication of a series of discoid, monodisperse, low-modulus hydrogel particles with diameters ranging from 0.8 to 8.9 μm, spanning sizes smaller than and larger than RBCs. We injected these particles into healthy mice, and tracked their concentration in the blood and their distribution into major organs. These deformable particles all demonstrated some hold up in filtration tissues like the lungs and spleen, followed by release back into the circulation, characterized by decreases in particles in these tissues with concomitant increases in particle concentration in blood. Particles similar to red blood cells in size demonstrated longer circulation times, suggesting that this size and shape of deformable particle is uniquely suited to avoid clearance.
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