Targeted delivery of PTX by lactoferrin-modified nanoemulsions for the treatment of glioblastoma

Glioblastoma treatment is hindered by the blood-brain barrier (BBB), which limits the penetration and accumulation of chemotherapeutic agents. Paclitaxel (PTX), an effective chemotherapeutic drug, faces clinical challenges due toits poor solubility and restricted ability to traverse the BBB. Consequently, there is an urgent need for advanced drug delivery systems to facilitate the efficient and safe translocation of PTX across the BBB. In this study, PTX was encapsulated within nanoemulsions (NEs) conjugated to lactoferrin (Lf) via electrostatic interactions, followed by the optimization of its formulation. To investigate cellular uptake and BBB penetration, fluorescent dye coumarin 6 (C6) was incorporated into NEs. Uptake was evaluated in GL261 cells and BBB penetration in hCMEC/D3 cells. Further studies were conducted on the biodistribution in mice and the therapeutic efficacy in murine intracranial glioblastoma model. Characterization of PTX@Lf-NE demonstrated stability, biological safety, and favorable release properties. Notably, the fluorescence intensity of C6@Lf-NE was twice of C6@NE in one hour post-administration, and the drug uptake rate decreased with the addition of free Lf, confirming that Lf promotes the ability of NEs to traverse the BBB. In vivo distribution further revealed that Lf-NE increased brain distribution while reduced accumulation in other organs. In the glioblastoma model, it was found that the bioluminescent intensity of PTX@Lf-NE was significantly lower than that of PTX@NE on the 15th day of administration, indicating that the modification with Lf facilitated the targeted delivery of PTX and enhanced its therapeutic efficacy. This study successfully designed and developed an effective drug delivery system for glioblastoma treatment, which improves the translocation of drugs across the BBB.