Ma Pin Pin, Li Zi Ling, Gao Hong Xia, Xiong Xiang Yuan
School of Life Science, Jiangxi Science and Technology Normal University, Jiangxi Key Laboratory of Natural Microbial Medicine Research, Key Laboratory of Microbial Resources and Metabolism of Nanchang City, Nanchang 330013, China.
School of Life Science, Jiangxi Science and Technology Normal University, Jiangxi Key Laboratory of Natural Microbial Medicine Research, Key Laboratory of Microbial Resources and Metabolism of Nanchang City, Nanchang 330013, China.
Eur J Pharm Biopharm. 2025 Sep;214:114761. doi: 10.1016/j.ejpb.2025.114761. Epub 2025 Jun 4.
The intestinal epithelium barrier is one of the main factors limiting the bioavailability of oral insulin delivery systems. Neonatal Fc (fragment crystallizable) receptor (FcRn) is highly expressed in the intestinal epithelium, which can bind specifically to the Fc fragments of IgG in a pH-dependent manner and thus improve the transepithelial transport of carriers modified by IgG Fc or Fc domain-binding peptides (FcBP) ligand. Thus, FcBP ligand was attached to Pluronic F127-polylactic acid polymersomes by using the biotin-avidin bridging technology to obtain FcRn-targeted FcBP-F127-PLA polymersomes. Insulin (INS) was loaded successfully into FcBP-F127-PLA with the loading efficiency of 12.01 %. The transepithelial transport experiments on Caco-2 cells using Coumarin-6 (C-6) as a fluorescence probe showed that the cumulative permeability percentage and apparent permeability coefficient (Papp) of theFcBP-F127-PLA/C-6 group was 1.7 and 1.8 times that of PLA-F127-PLA/C-6 group after 2 h of incubation, respectively. FcBP ligand density of FcBP-F127-PLA played a role on their transepithelial transport ability and 10%FcBP-F127-PLA with 10 % FcBP molar content was found to be the best. The in vivo hypoglycemic results showed that the relative pharmacological bioavailability (PA%) of theoral 10%FcBP-F127-PLA/INS group was 43.6 %, which was 1.27 times that of the PLA-F127-PLA/INS group. Therefore, FcBP-F127-PLA polymersomes could be a promising carrier of the oral insulin delivery.
肠道上皮屏障是限制口服胰岛素递送系统生物利用度的主要因素之一。新生儿Fc（可结晶片段）受体（FcRn）在肠道上皮中高度表达，它可以以pH依赖的方式特异性结合IgG的Fc片段，从而改善由IgG Fc或Fc结构域结合肽（FcBP）配体修饰的载体的跨上皮转运。因此，利用生物素-抗生物素蛋白桥接技术将FcBP配体连接到普朗尼克F127-聚乳酸聚合物囊泡上，以获得靶向FcRn的FcBP-F127-PLA聚合物囊泡。胰岛素（INS）成功负载到FcBP-F127-PLA中，负载效率为12.01%。以香豆素-6（C-6）作为荧光探针在Caco-2细胞上进行的跨上皮转运实验表明，孵育2小时后，FcBP-F127-PLA/C-6组的累积渗透百分比和表观渗透系数（Papp）分别是PLA-F127-PLA/C-6组的1.7倍和1.8倍。FcBP-F127-PLA的FcBP配体密度对其跨上皮转运能力有影响，发现FcBP摩尔含量为10%的10%FcBP-F127-PLA是最佳的。体内降血糖结果表明，口服10%FcBP-F127-PLA/INS组的相对药理生物利用度（PA%）为43.6%，是PLA-F127-PLA/INS组的1.27倍。因此，FcBP-F127-PLA聚合物囊泡可能是一种有前途的口服胰岛素递送载体。
