Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China.
Biomaterials. 2013 Jul;34(20):4818-30. doi: 10.1016/j.biomaterials.2013.03.013. Epub 2013 Mar 29.
83-14 monoclonal antibody (MAb) was modified on solid lipid nanoparticles (SLNs) to improve the brain-targeting delivery of saquinavir (SQV). The endocytosis of 83-14 MAb-grafted SQV-loaded SLNs (83-14 MAb/SQV-SLNs) into human brain-microvasscular endothelial cells (HBMECs) was studied by staining cell nuclei, insulin receptors, and drug carriers. An increase in the weight fraction of palmitic acid in lipid core enhanced the particle size, absolute value of zeta potential, and viability of HBMECs and reduced the entrapment efficiency and release rate of SQV. In addition, an increase in the weight fraction of poloxamer 407 in surfactant layer reduced the particle size, absolute value of zeta potential, phagocytosis by RAW246.7 cells, permeability across the blood-brain barrier (BBB), and uptake by HBMECs and enhanced the viability of HBMECs. Moreover, an increase in the concentration of surface 83-14 MAb enhanced the percentage of surface nitrogen, permeability across the BBB, and uptake by HBMECs and did not significantly vary the viability of HBMECs and phagocytosis by RAW264.7 cells. 83-14 MAb/SQV-SLNs can ameliorate the bioavailability characteristics of SQV, inhibit the lymphatic particle uptake, and promote the transport of SQV into brain endothelia.
83-14 单克隆抗体 (MAb) 被修饰在固体脂质纳米粒 (SLNs) 上，以提高沙奎那韦 (SQV) 的脑靶向递送。通过染色细胞核、胰岛素受体和药物载体研究了 83-14 MAb 接枝的载有 SQV 的 SLNs (83-14 MAb/SQV-SLNs) 进入人脑微血管内皮细胞 (HBMECs) 的内吞作用。脂质核中棕榈酸的重量分数增加会增加颗粒大小、HBMECs 的绝对 zeta 电位和活力，降低 SQV 的包封效率和释放率。此外，表面活性剂层中聚氧乙烯 407 的重量分数增加会降低颗粒大小、绝对 zeta 电位、RAW246.7 细胞的吞噬作用、血脑屏障 (BBB) 的通透性和 HBMECs 的摄取，并增强 HBMECs 的活力。此外，表面 83-14 MAb 浓度的增加会提高表面氮的百分比、BBB 的通透性和 HBMECs 的摄取，而对 HBMECs 的活力和 RAW264.7 细胞的吞噬作用没有显著影响。83-14 MAb/SQV-SLNs 可以改善 SQV 的生物利用度特征，抑制淋巴颗粒摄取，并促进 SQV 向脑内皮的转运。
