Electro-responsive brain-targeting mixed micelles based on Pluronic F127 and D-α-tocopherol polyethylene glycol succinate-ferrocene

Treatment efficacy for brain diseases is unsatisfactory because most drugs have low bioavailability and it's difficult for these drugs to cross the blood-brain barrier (BBB). Nanocarriers have the potential to promote drug delivery to the brain. Moreover, drug release from smart nanocarriers can be precisely controlled by responding to both exogenous and endogenous stimuli. Herein we newly constructed brain-targeting electro-responsive micelles based on Pluronic F127 and D-alpha-tocopherol polyethylene glycol succinate (TPGS) conjugated with an electro-sensitive group ferrocene (Fc) (TPGS-Fc), obtaining Pluronic F127/TPGS-Fc mixed micelles. Insoluble drugs can be encapsulated into the hydrophobic blocks of Pluronics and TPGS, as well as reduced Fc group. Because oxidation of reduced Fc by current can convert the hydrophobic group to hydrophilic one, electrical stimulation triggered micelles disassembly and corresponding drug release. The micellar carriers showed excellent biocompatibility due to the inherent safety of F127 and TPGS polymers. Fluorescent rhodamine 123- and DiR-loaded micelles demonstrated potent brain-targeting ability of the drug delivery system in vitro and in vivo, respectively. Controlled drug release responding to electrical stimulation in vivo was also confirmed by loading P2 probes (a novel water-quenching fluorescent probe). Our study revealed that the brain-targeting electro- responsive micelles have promising potential as candidate drug delivery system to the brain and warrant further assessment and development.