Targeting nevirapine delivery across human brain microvascular endothelial cells using transferrin-grafted poly(lactide-co-glycolide) nanoparticles

摘要

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.