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.
ACS Appl Mater Interfaces. 2017 Jul 5;9(26):21660-21672. doi: 10.1021/acsami.7b04916. Epub 2017 Jun 23.
The in vivo translocation of nanoemulsions (NEs) was tracked by imaging tools with an emphasis on the size effect. To guarantee the accurate identification of NEs in vivo, water-quenching environment-responsive near-infrared fluorescent probes were used to label NEs. Imaging evidence confirmed prominent digestion in the gastrointestinal tract and oral absorption of integral NEs that survive digestion by enteric epithelia in a size-dependent way. In general, reducing particle size leads to slowed in vitro lipolysis and in vivo digestion, a prolonged lifetime in the small intestine, increased enteric epithelial uptake, and enhanced transportation to various organs. Histological examination revealed a pervasive distribution of smaller NEs (80 nm) into enterocytes and basolateral tissues, whereas bigger ones (550, 1000 nm) primarily adhered to villi surfaces. Following epithelial uptake, NEs are transported through the lymphatics with a fraction of approximately 3-6%, suggesting a considerable contribution of the lymphatic pathway to overall absorption. The majority of absorbed NEs were found 1 h post administration in the livers and lungs. A similar size dependency of cellular uptake and transmonolayer transport was confirmed in Caco-2 cell lines as well. In conclusion, the size-dependent translocation of integral NEs was confirmed with an absolute bioavailability of at least 6%, envisioning potential applications in oral delivery of labile entities.
采用成像工具追踪纳米乳剂（NEs）的体内移位，重点关注粒径效应。为了保证在体内准确识别 NEs，使用水猝灭环境响应近红外荧光探针对 NEs 进行标记。成像证据证实，完整的 NEs 在胃肠道中显著消化，并以依赖于粒径的方式通过肠上皮进行口服吸收。一般来说，降低颗粒尺寸会导致体外脂肪分解和体内消化减慢、在小肠中的寿命延长、肠上皮摄取增加以及向各种器官的转运增强。组织学检查显示，较小的 NEs（80nm）普遍分布在肠细胞和基底外侧组织中，而较大的 NEs（550nm、1000nm）主要附着在绒毛表面。上皮摄取后，NEs 通过淋巴途径转运，约有 3-6%的比例，这表明淋巴途径对整体吸收有相当大的贡献。吸收的 NEs 大部分在给药后 1 小时内出现在肝脏和肺部。在 Caco-2 细胞系中也证实了细胞摄取和跨单层转运的类似粒径依赖性。总之，完整的 NEs 的粒径依赖性移位得到了证实，其绝对生物利用度至少为 6%，为不稳定实体的口服递药设想了潜在的应用。
