Carmustine-loaded catanionic solid lipid nanoparticles with serotonergic 1B receptor subtype antagonist for in vitro targeted delivery to inhibit brain cancer growth

Solid lipid nanoparticles (SLNs) stabilized with catanionic surfactants and grafted with serotonergic 1B receptor subtype antagonist (S1BRSA) were employed to encapsulate carmustine (BCNU) (denoted as S1BRSA/BCNU-CASLNs) for brain-targeted delivery. BCNU-CASLNs were fabricated by microemulsion method and the monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes were treated with S1BRSA/BCNU-CASLNs to evaluate the BCNU permeability across the blood-brain barrier. An increase in the catanionic surfactant concentration promoted the surface charge and toxicity to HBMECs and U87MG cells of glioblastoma multiforme (GBM). The catanionic surfactant concentration at 1 mM yielded the smallest particle size and highest entrapment efficiency of BCNU. An increase in the weight percentage of Compritol 888 ATO (CA) reduced the particle size and surface charge and enhanced the grafting efficiency of S1BRSA, viability of HBMECs, and BCNU permeability. A maximal entrapment efficiency of BCNU emerged at 50% (w/w) CA. An increase in the S1BRSA concentration reduced the grafting efficiency of S1BRSA and improved the BCNU permeability. The developed S1BRSA/BCNU-CASLNs, showing an anticancer efficacy against the growth of malignant GBM U87MG cells, were efficacious carriers in delivering BCNU to HBMECs and could be administered by intravenous injection in clinical application.