Chen Fu, Zhang Zhi-Rong, Yuan Fang, Qin Xuan, Wang Minting, Huang Yuan
Key Laboratory of Drug Targeting of Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
Int J Pharm. 2008 Feb 12;349(1-2):226-33. doi: 10.1016/j.ijpharm.2007.07.035. Epub 2007 Aug 2.
In this study, the effects of alginate modification on absorption properties of FITC-BSA loaded TMC nanoparticles were investigated on an in vitro model of GI epithelium (Caco-2 cells). The feasibility of applying TMC nanoparticles loaded with a model vaccine urease in oral vaccination was also studied. Alginate modified TMC nanoparticles showed higher FITC-BSA permeate efficiency than non-modified TMC nanoparticles. However, alginate modification barely had any effect on TMC nanoparticles' property of decreasing TEER or enhancing drug paracellular transport. Mice s.c. immunized with urease loaded TMC nanoparticles showed highest systematic immune response (IgG levels) but the lowest mucosal response (secretory IgA levels). In the contrast, mice i.g. immunized with urease loaded TMC nanoparticles showed much higher antibody titers of both IgG and secretory IgA than those with urease solution or urease co-administrated with TMC solution. These results indicated that TMC nanoparticles are potential carriers for oral protein and vaccine delivery.
在本研究中，在胃肠道上皮细胞（Caco-2细胞）的体外模型上研究了海藻酸盐修饰对负载异硫氰酸荧光素标记牛血清白蛋白（FITC-BSA）的三聚氰胺甲醛共聚物（TMC）纳米颗粒吸收特性的影响。还研究了口服接种负载模型疫苗脲酶的TMC纳米颗粒的可行性。海藻酸盐修饰的TMC纳米颗粒比未修饰的TMC纳米颗粒表现出更高的FITC-BSA渗透效率。然而，海藻酸盐修饰对TMC纳米颗粒降低跨上皮电阻（TEER）或增强药物细胞旁转运的特性几乎没有任何影响。皮下注射负载脲酶的TMC纳米颗粒免疫的小鼠表现出最高的全身免疫反应（IgG水平），但黏膜反应最低（分泌型IgA水平）。相比之下，口服接种负载脲酶的TMC纳米颗粒免疫的小鼠，其IgG和分泌型IgA的抗体滴度均远高于接种脲酶溶液或脲酶与TMC溶液共同给药的小鼠。这些结果表明，TMC纳米颗粒是口服蛋白质和疫苗递送的潜在载体。
