纳米紫杉醇在人源肠Caco-2细胞模型的吸收转运研究(英文)

Nano-paclitaxel Transport by Human Intestinal Epithelial Caco-2 Cells

大量的研究已经证明,紫杉醇口服吸收较差,容易引起过敏性反应。为了克服紫杉醇的不足,我们制备了一种新的纳米紫杉醇药物,它由甘露醇与人血清白蛋白包裹紫杉醇颗粒制成,其具有更好的水溶性和较低的毒性。为了进一步研究纳米紫杉醇口服给药后的吸收效果,我们利用Caco-2细胞模型对纳米紫杉醇的跨膜转运量进行了测定,3 h内,纳米紫杉醇在0.5～20μmol.L-1的浓度内的转运量呈线性状态。从膜的顶端到底端的表观渗透系数Papp为(20.9±2.1×10-6cm.s-1;N=3),米氏方程常数KM值为相对较高的14.00μmol.L-1,这些数据表明纳米紫杉醇具有更好的吸收效果。

Many studies had proved that oral administration of paclitaxel was poorly absorbed and easy to cause hypersensitiyity reactions. For this reason, we produced a new nano-paclitaxel by paclitaxel granule wrapped with mannitol and Human Serum Albumin （HSA）, which had better water solubility and lower systemic toxicity. In order to research the absorption of nano-paclitaxel after oral administration, the transepithelial flux of nano- paclitaxel was studied using the human colonic cell line Caeo-2 cells. The flux of nano-paclitaxel （at a concentration range of 0.5 - 20μmol·L^-1 ） across the Caco-2 cell layer was linear with time for up to 3 h. The apparent permeability coefficient （Papp） for the apical to basolateral transport of nano-paclitaxel （20.9 ± 2.1 × 10-6 cm· s^-1 ; N = 3 ） and the apparent maximal concentration （ KM ） of the active efflux component （ 14.00 μmol·L^-1 ） were relatively high, suggesting that nano-paelitaxel may have a better absorption rate in the intestinal tract.