School of Pharmacy, Shanghai University of Traditional Chinese Medicine，Shanghai, China.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine，Shanghai, China.
Nanomedicine. 2019 Oct;21:102075. doi: 10.1016/j.nano.2019.102075. Epub 2019 Aug 1.
To improve Biopharmaceutics Classification System class IV drug bioavailability, mucus and underlying intestinal epithelial barriers must be overcome. Hydrophilic nanoparticle coatings may hinder cellular uptake and transport. We integrated hydrophilic, detachable poly(N-(2-hydroxypropyl) methacrylamide) with vitamin B12-modified chitosan into lipid polymeric nanoparticles (H/VC-LPNs) to enhance mucus penetration, intracellular uptake, and transepithelial absorption. Multiple particle tracking revealed accelerated mucus diffusion into porcine mucus in vitro. The nanoparticles increased uptake and intracellular distribution in Caco-2 cells, which may involve intrinsic factor receptor-mediated endocytosis and intercellular tight junctions. Integration of improved mucus penetration and intracellular absorption was confirmed by in vitro internalization kinetics in HT29-MTX/Caco-2 co-cultures and in vivo distribution, transport, and mouse Peyer's patch absorption. H/VC-LPNs substantially increased curcumin bioavailability in rats. A nanocarrier with a dissociable shell, receptor-mediated intracellular penetration, and paracellular transport may be promising for oral curcumin delivery. This study identified the key factors involved in oral bioavailability enhancement.
为了提高生物药剂学分类系统第四类药物的生物利用度，必须克服黏液和肠道上皮屏障。亲水性纳米颗粒涂层可能会阻碍细胞摄取和转运。我们将亲水性、可分离的聚（N-（2-羟丙基）甲基丙烯酰胺）与维生素 B12 修饰壳聚糖整合到脂质聚合物纳米颗粒（H/VC-LPN）中，以增强黏液穿透、细胞内摄取和跨上皮吸收。多颗粒跟踪显示，纳米颗粒在体外加速了猪黏液的扩散。这些纳米颗粒增加了 Caco-2 细胞的摄取和细胞内分布，这可能涉及内因子受体介导的胞吞作用和细胞间紧密连接。通过 HT29-MTX/Caco-2 共培养物中的体外内化动力学以及体内分布、转运和小鼠派尔集合淋巴结吸收证实了改进的黏液穿透和细胞内吸收的整合。H/VC-LPN 显著提高了姜黄素在大鼠体内的生物利用度。具有可分离外壳、受体介导的细胞内穿透和细胞旁转运的纳米载体可能是口服姜黄素递送的有前途的候选物。本研究确定了提高口服生物利用度的关键因素。
