Pinto-Alphandary Huguette, Aboubakar Malam, Jaillard Danielle, Couvreur Patrick, Vauthier Christine
UMR CNRS 8612, Laboratoire de Physico-Chimie, Pharmacotechnie et Biopharmacie, Faculté de Pharmacie, Université Paris XI, 92296 Châtenay-Malabry Cédex, France.
Pharm Res. 2003 Jul;20(7):1071-84. doi: 10.1023/a:1024470508758.
Biodegradable poly(isobutylcyanoacrylate) nanocapsules have been recognized as a promising carrier for oral administration of peptides and proteins. In the present study, we investigate the fate of insulin-loaded nanocapsules by fluorescence and transmission electron microscopy (TEM) after intragastric force-feeding to rats.
Insulin-, Texas-red-labeled insulin, or gold-labeled insulin-loaded nanocapsules were first characterized. Rats received a single dose of nanocapsules (diameter 60-300 nm, 57 IU insulin/kg) by intragastric force-feeding. After 90 min, ileum was isolated and prepared for fluorescence and transmission electron microscopy.
Nanocapsules were observed on both sides of the gut epithelium and in blood capillaries. In M-cell-free epithelium, apparently intact nanocapsules could be seen in the underlying tissue, suggesting they could cross the epithelium and carry the encapsulated peptide. In M-cell-containing epithelium, nanocapsules appeared degraded in the vicinity of macrophages. It is noteworthy that intestinal absorption of nanocapsules was observed without artifacts forcing the nanocapsules to stay in the gut.
Based on TEM observations, this study shows the intestinal absorption of biodegradable nanocapsules leading to the transport of insulin across the epithelium mucosa. The fate of the nanocapsules appeared different depending on the presence or the absence of M cells in the intestinal epithelium.
可生物降解的聚异丁基氰基丙烯酸酯纳米胶囊已被认为是口服肽和蛋白质的一种有前景的载体。在本研究中，我们通过荧光和透射电子显微镜（TEM）研究了给大鼠灌胃强制喂食胰岛素负载纳米胶囊后的命运。
首先对负载胰岛素、Texas红标记胰岛素或金标记胰岛素的纳米胶囊进行表征。大鼠通过灌胃强制喂食单剂量纳米胶囊（直径60 - 300 nm，57 IU胰岛素/千克）。90分钟后，分离回肠并制备用于荧光和透射电子显微镜观察。
在肠上皮两侧和毛细血管中均观察到纳米胶囊。在无M细胞的上皮中，在其下方组织中可见明显完整的纳米胶囊，表明它们可以穿过上皮并携带包封的肽。在含M细胞的上皮中，纳米胶囊在巨噬细胞附近出现降解。值得注意的是，观察到纳米胶囊的肠道吸收，且没有人为因素迫使纳米胶囊留在肠道内。
基于TEM观察，本研究表明可生物降解纳米胶囊的肠道吸收导致胰岛素穿过上皮黏膜转运。纳米胶囊的命运似乎因肠道上皮中是否存在M细胞而有所不同。
