Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng, 475001, China.
Adv Healthc Mater. 2018 Nov;7(22):e1800711. doi: 10.1002/adhm.201800711. Epub 2018 Oct 21.
The limited information on biological fate impedes the development of more efficient polymeric nanoparticles for oral delivery of bio-macromolecules. In this study, the in vivo fate as well as the trans-epithelia transport of polycaprolactone (PCL) nanoparticles is explored by labeling with aggregation-caused quenching probes, which is capable of identifying intact nanoparticles. Live imaging and confocal laser scan microscopy confirm size-dependent absorption of PCL nanoparticles. In general, reducing particle size favors a faster and more oral absorption. Nanoparticles larger than 200 nm, such as 600 and 2000 nm, cannot be efficiently transported across the intestinal membrane. The absorbed nanoparticles (50 and 200 nm) mainly accumulate in the liver. Lymph may be the main absorption route for PCL nanoparticles, transporting 2.39 ± 1.81% and 0.98 ± 0.58% of administered 50 and 200 nm nanoparticles, respectively. Cellular uptake and transportation of PCL nanoparticles are also size dependent. Both enterocytes and M cells mediated transcytosis are involved in the transport of 50 nm PCL nanoparticles, while the M cell pathway is dominative for other nanoparticles. In conclusion, the study provides a valuable tool for bioimaging of intact polymeric nanoparticles as well as solid evidence supporting size-dependent translocation of the nanoparticles via oral delivery.
体内生物命运及聚己内酯（PCL）纳米粒的跨上皮转运研究
有限的生物命运信息阻碍了更高效的聚合物纳米粒用于生物大分子的口服给药。在这项研究中，通过使用聚集诱导猝灭探针进行标记，探索了聚己内酯（PCL）纳米粒的体内命运以及跨上皮转运，这种方法能够识别完整的纳米粒。活体成像和共聚焦激光扫描显微镜证实了 PCL 纳米粒的尺寸依赖性吸收。一般来说，减小颗粒尺寸有利于更快、更口服吸收。大于 200nm 的纳米粒，如 600nm 和 2000nm，不能有效地穿过肠膜运输。吸收的纳米粒（50nm 和 200nm）主要积聚在肝脏中。淋巴可能是 PCL 纳米粒的主要吸收途径，分别输送 50nm 和 200nm 纳米粒给药量的 2.39±1.81%和 0.98±0.58%。PCL 纳米粒的细胞摄取和转运也与尺寸有关。肠细胞和 M 细胞介导的转胞吞都参与了 50nm PCL 纳米粒的转运，而其他纳米粒的转运途径则以 M 细胞途径为主。总之，该研究为完整聚合物纳米粒的生物成像提供了有价值的工具，并为口服给药时纳米粒的尺寸依赖性转位提供了确凿的证据。
