Development of lactoferrin-coated multifunctional copolymer micelles to cross the blood-brain barrier

In this study, we prepared and evaluated a novel nano-delivery vehicle system composed of lactoferrin-conjugated (Lf-PIC@Se) micelles. We used a COOH-PEG-PAsp-PV@Se synthesis-based method to prepare the micelles, which involved self-assembly followed by EDC-NHS coupling. Using glutaminyl cyclase inhibitor 8 as a model encapsulated chemical, Lf-PIC@Se micelles achieved a good loading capacity. In vitro analysis demonstrated that Lf-PIC@Se/8 micelles were stable in both neutral and acidic pH solutions in the presence or absence of H2O2, and confirmed their biosafety and compatibility in PC12 and bEND.3 cells. Notably, the cell uptake of Lf-PIC@Se/C6 micelles was much higher than that of PIC@Se micelles, and occurred through LfR-mediated endocytosis. The presence of Se meant that Lf-PIC@Se micelles acted as ROS scavengers in PC12 cells under H2O2-induced oxidative stress, which inhibited oxidative damage and increased mitochondrial membrane potential. Hemolysis assays further demonstrated that Lf-PIC@Se represent a biocompatible carrier. Finally, in vivo experiments in mice suggested that Lf-PIC@Se micelles successfully crossed the BBB, confirming their potential as vehicles for drug delivery when treating AD and other central nervous system disorders.PMID:37721695 | DOI:10.1007/s13346-023-01432-6
Source: Cell Research - Category: Cytology Authors: Source Type: research