Targeting Nevirapine Delivery Across Human Brain Microvascular Endothelial Cells Using Transferrin-Grafted Poly(Lactide- Co -Glycolide) Nanoparticles

AIMS: Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were grafted with transferrin (Tf) to enhance the transport of nevirapine (NVP) across human brain microvascular endothelial cells (HBMECs). METHODS: NVP-loaded PLGA NPs with surface-grafting Tf (Tf/NVP-PLGA NPs) were incubated with HBMECs and immunochemical staining characterized Tf receptors (TfRs). RESULTS: The polydispersity index of Tf/NVP-PLGA NPs was lower than 0.008. The entrapment efficiency of NVP and loading efficiency of Tf was 20-75% and 15-80%, respectively. Tf slightly retarded the release of NVP from PLGA. Dioctadecyldimethylammonium bromide (DODAB)-stabilized Tf/NVP-PLGA NPs reduced the viability of HBMECs to 70-75%. The secretion of TNF-α was inhibited by Tf and stimulated by DODAB. The permeability of NVP across HBMECs reached maxima at 67% DODAB and 0.1-0.2% Tf. An increase in the concentration of Tf enhanced the uptake of Tf/NVP-PLGA NPs via a TfR-mediated mechanism. CONCLUSION: Tf/NVP-PLGA NPs are efficacious carriers in targeting delivery across HBMECs for viral therapy.