Fig. 6
In vivo studies of self-implantable double-layered microneedles. a A polymeric patch containing 3 × 3 DL-MNs was applied on the central region of mouse eye (~30 s). b Bright-field images of the patch, before (left) and after (right) insertion into the eye, are shown. Scale bars = 200 µm. c In vivo imaging of the eyes, applied without (left) or with IgG(680)-loaded MN patch (right). d, e Bright field images of the eye treated with a IgG(680)-loaded MN patch, at day 0 (immediately after insertion) and at day 3 (d). The red fluorescence spots in the cornea mark the penetration sites (e). Scale bar = 500 µm. f The representative histological changes of mouse cornea, at day 0, day 1, day 3 or day 7 after MN patch application. Scale bar = 100 µm. g–i The weight (g), food intake (h), and the grimace scale for pain assessment (i) were examined at day 0 (2 h after insertion), day 1, day 3 or day 7 after patch application. Data represent mean ± SEM (n = 5). j, k In vivo distribution of IgG in mice, treated without (control) or with systemic injection (intraperitoneal, I.P.), eye drop (ED) (one-side only) or MN patch application (one side only) of IgG(680). The representative fluorescence images of dissected organs, 2 h after treatment, are shown in (j). The quantitative analysis (mean ± SEM; n = 5) of fluorescent intensities of eyes treated with MN patch at day 0 and day 3 is shown in (k). n represents the number of samples for each group
