文献：

Raloxifene/SBE-β-CD Inclusion Complexes Formulated into Nanoparticles with Chitosan to Overcome the Absorption Barrier for Bioavailability Enhancement

文献链接：

https://pubmed.ncbi.nlm.nih.gov/29958389/

作者：

Zaihua Wang and Yan Li

相关产品：

cy3-壳聚糖

原文摘要：Raloxifene (RXF) is a hormone-like medication used for treating postmenopausal

osteoporosis and estrogen-dependent breast cancer, yet associated with bad low bioavailability due to poor solubility. This study was intended to develop cyclodextrin/chitosan nanoparticles (ccNPs) for oral delivery of RXF in order to enhance the oral bioavailability. RXF-loaded ccNPs (RXF-ccNPs) were prepared by cyclodextrin inclusion followed by complexation with chitosan. RXF-ccNPs were fully characterized by particle size, morphology and in vitro drug release. The oral delivery efficacy and transepithelial transport potential were evaluated by pharmacokinetics, in situ single-pass intestinal perfusion, cellular uptake and ex vivo imaging. The resulting RXF-ccNPs were around 165 nm in particle size with a narrow distribution. The oral bioavailability of RXF was enhanced by 2.6 folds through ccNPs compared to RXF suspensions in rats. It was shown that RXF-ccNPs could improve the intestinal permeability of RXF, increase the cellular uptake of RXF and facilitate its transport across the absorptive epithelia. The results indicate that our developed ccNPs based on sulfobutylether-β-cyclodextrin and oligochitosan are a promising vehicle to orally deliver poorly water-soluble drugs over and above RXF.

雷洛昔芬（RXF）是一种激素样化合物，但由于溶解度差而与不良的低生物利用度相关，所以制备了RXF的环糊精/壳聚糖纳米颗粒（ccNPs），以提高其利用度。采用cy3-壳聚糖标记环糊精包合体和壳聚糖络合法制备了负载RXF的ccNPs（RXF-ccNPs）。RXF-ccNPs的颗粒大小、形态和体外化合物释放具有充分的表征。

经上皮运输的体外成像

通过肠组织切片的体外成像，检测RXF-ccNPs的经上皮转运特性。荧光RXF-ccNPs是通过在RXF-ccNPs的配方中加入少量的cy3-壳聚糖来制备的。大鼠禁食过夜，然后口服荧光RXF-ccNPs。两小时后，处理大鼠，切下0.5 cm小肠组织，用冰水生理盐水冲洗。用4%多聚甲醛固定干净的肠段，然后制成石蜡片。通过CLSM观察RXF-ccNPs在吸收上皮中的荧光分布。

图：用CLSM检测口服cy3标记的RXF-ccNPs后肠组织切片的体外成像

结论：RXF可以很好地包含在SBE-β-CD中，并通过静电相互作用与寡聚糖进一步形成纳米颗粒。所得到的纳米颗粒（cc-NPs）具有较小的颗粒尺寸，并表现出持续的化合物释放。RXF通过cc-NPs明显提高了其利用度，相对于RXF悬液高达3.6倍。cy3-壳聚糖标记的RXF-ccNPs具有较高的通透性、良好的细胞摄取和生物相容性。