Targeting delivery of saquinavir to the brain using 83-14 monoclonal antibody-grafted solid lipid nanoparticles

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. (C) 2013 Elsevier Ltd. All rights reserved.