Construction of MPTP-induced PD mouse model

Based on the intact BBB, MPTP-induced PD mouse model was chosen for all experiments. The C57BL/6 mice were treated by repeated intraperitoneal injections (i.p.) of MPTP (40 mg/kg) solution for 7 days consecutively. The mice were randomly divided into 5 groups ^{5, 13}: (1) control; (2) only curcumin-loaded cerasomes with no PS 80; (3) Only CPC with 5% PS 80; (4) 5% PS 80 modified cerasomes with no curcumin in combination with UTMD; (5) CPC with 5% PS 80 in combination with UTMD (15 mg/kg curcumin was administered with 2×10⁸ MBs/kg). The mice were treated every two days for four times to ensure effective drug accumulation in the brain. For the groups with UTMD application, the mice were depilated under 10% chloral hydrate anesthesia (10 g/100 mL normal saline, 4 mL/kg i.p.), and were then mounted onto a stereotactic frame. The focus point of the ultrasonic probe was firstly set at the bregma as the original point and then adjusted precisely to the corpus striatum in medial forebrain bundle (MFB), referred to as the brain atlas. The focused ultrasound beam was generated by a single-element spherical transducer (center frequency: 1.2819 MHz; focal length: 51.3 mm; cycle: 10.000 k), a function generator (AFG3102C, Tektronix, Beaverton, USA), and was driven by a 50 dB power amplifier (325LA, Electronics & Innovation, Rochester, USA) according to the reported research ⁶⁴. The ultrasound was performed for 60 s on both sides of the brain after different administrations i.v.