Solid lipid nanoparticles with surface antibody for targeting the brain and inhibiting lymphatic phagocytosis

• A maximum entrapment of saquinavir occurred at 33% (w/w) Dynasan 114.
• An increase in the weight percentage of Dynasan 114 enhances the grafting of monoclonal antibody.
• Surface Tween 80 and Poloxamer 407 benefit the viability of RAW264.7 cells.
• Poloxamer 407-stabilized solid lipid nanoparticles inhibit phagocytosis by RAW264.7 cells.
• Grafted monoclonal antibody on solid lipid nanoparticles favors the brain-targeted delivery.

Solid lipid nanoparticles (SLNs) with surface monoclonal antibody (MAb), poloxamer 407 (P407), and polysorbate 80 (Tween 80) (defined as P-T-MAb/SQV-SLNs) were used to enhance the transport efficacy of antiviral saquinavir (SQV) across the blood–brain barrier (BBB). Internalizations of P-T-MAb/SQV-SLNs by RAW264.7 cells and by human brain-microvascular endothelial cells were quantified by chemical assay and examined by immunochemical staining. The results revealed that a decrease in the weight percentage of Dynasan 114 (DYN) in internal lipids, comprising DYN, palmitic acid, and cacao butter, increased the particle size and zeta potential of P-T-MAb/SQV-SLNs. In addition, the external P407 and Tween 80 could stabilize P-T-MAb/SQV-SLNs and reduce phagocytosis by RAW264.7 cells. Tween 80 on P-T-MAb/SQV-SLNs also benefited the delivery of SQV across the BBB. Moreover, MAb grafted on P-T-MAb/SQV-SLNs promoted the permeability of SQV across the blood–brain barrier. The grafting of MAb and coating of P407 and Tween 80 on the surface of SLNs demonstrate an effective strategy to prevent phagocytosis by RAW264.7 cells and to promote the targeting delivery of SQV across the BBB for inhibiting retroviral growth.