Université Catholique de Louvain, Unité de Pharmacie Galénique, Brussels, Belgium.
Eur J Pharm Biopharm. 2009 Sep;73(1):16-24. doi: 10.1016/j.ejpb.2009.04.009. Epub 2009 May 4.
The presence of RGD on nanoparticles allows the targeting of beta1 integrins at the apical surface of human M cells and the enhancement of an immune response after oral immunization. To check the hypothesis that non-peptidic ligands targeting intestinal M cells or APCs would be more efficient for oral immunization than RGD, novel non-peptidic and peptidic analogs (RGD peptidomimitic (RGDp), LDV derivative (LDVd) and LDV peptidomimetic (LDVp)) as well as mannose were grafted on the PEG chain of PCL-PEG and incorporated in PLGA-based nanoparticles. RGD and RGDp significantly increased the transport of nanoparticles across an in vitro model of human M cells as compared to enterocytes. RGD, LDVp, LDVd and mannose enhanced nanoparticle uptake by macrophages in vitro. The intraduodenal immunization with RGDp-, LDVd- or mannose-labeled nanoparticles elicited a higher production of IgG antibodies than the intramuscular injection of free ovalbumin or intraduodenal administration of either non-targeted or RGD-nanoparticles. Targeted formulations were also able to induce a cellular immune response. In conclusion, the in vitro transport of nanoparticles, uptake by macrophages and the immune response were positively influenced by the presence of ligands at the surface of nanoparticles. These targeted-nanoparticles could thus represent a promising delivery system for oral immunization.
RGD 存在于纳米粒子上，使得β1 整合素能够靶向人 M 细胞的顶端表面，并在口服免疫后增强免疫反应。为了验证靶向肠道 M 细胞或 APC 的非肽配体比 RGD 更适合口服免疫的假设，我们将新型非肽和肽类似物（RGD 肽模拟物（RGDp）、LDV 衍生物（LDVd）和 LDV 肽模拟物（LDVp））以及甘露糖接枝到 PCL-PEG 的 PEG 链上，并将其纳入基于 PLGA 的纳米颗粒中。与肠细胞相比，RGD 和 RGDp 显著增加了纳米颗粒在体外人 M 细胞模型中的转运。RGD、LDVp、LDVd 和甘露糖增强了纳米颗粒在体外被巨噬细胞摄取。与肌肉内注射游离卵清蛋白或十二指肠内给予非靶向或 RGD 纳米颗粒相比，用 RGDp、LDVd 或甘露糖标记的纳米颗粒进行十二指肠内免疫会引起更高水平的 IgG 抗体产生。靶向制剂还能够诱导细胞免疫反应。总之，纳米颗粒的体外转运、巨噬细胞的摄取以及免疫反应都受到纳米颗粒表面配体的积极影响。因此，这些靶向纳米颗粒可能是口服免疫的一种有前途的递药系统。
