Fig. 6: Assessment of in-brain drug delivery by microneedles.

The drug delivery analysis of melatonin-loaded microneedle (Mel-MN) is illustrated from a–d, and melatonin-loaded microneedle with 200-nm gold encapsulation (Au-Mel-MN) from e to h. a, e Schematic illustration of recording brain states by implanting the microneedle and electrodes after 1 week in mice. The microneedle is implanted into the medial prefrontal cortex (mPFC) of mice brain, while electrodes for signal recording are chronically implanted through the skull (for electroencephalogram, EEG) or into trapezius muscles (for electromyography, EMG). The microneedle in a and e are both loaded with 25 wt% melatonin (Mel-MN), while the microneedle in e is further coated with a 200-nm gold layer (Au-Mel-MN). b, f EEG power density analysis. The recording is a 3-h period from 19:00 to 22:00 in b–d and a 6-h period from 19:00-1:00 in f–h. c, g Time course of different brain states (active period) immediately after the light turns off. The lengths of non-rapid eye movement (NREM) sleep, wakefulness, and rapid eye movement (REM) sleep are calculated every 30 min. Two groups of 5 mice (melatonin-delivered mice and the control, respectively) are compared, where melatonin-delivered mice showed longer NREM sleep and shorter wakefulness in both c and g. The implanted Au-Mel-MN showed a more substantial effect of melatonin, suggesting the delayed release of melatonin as a result of gold protection. d, h Duration of different brain states (NREM, wake, and REM) during the recording time, corresponding to c and g, respectively. Data in c, d, g, h are presented as mean values +/− SEM of peak amplitude (n = 5 in all melatonin loaded and control groups) Paired two-sided t-tests are used for comparisons between the two groups in d, h, b, and f. Two-way ANOVAs are used to perform group comparisons with Sidak’s multiple comparisons test in c and g. All statistical tests were two-tailed. Source data are provided as a Source Data file, where time duration in c, d and g, h is counted in half-minute units.