Delivery and diffusion of retinal in dermis and epidermis through the combination of prodrug nanoparticles and detachable dissolvable microneedles

To minimize chemical degradation of retinal, we graft this aldehyde on chitosan chains to make them self-assemble into pro-retinal nanoparticles (PRNs), which we then load into detachable dissolvable microneedles (DDMNs) made of 1:1 (by weight) hyaluronic acid/maltose. The presence of PRNs in the hyaluronic acid-maltose needle matrix also helps improve the microneedles’ mechanical strength. Ex vivo administration of PRN-loaded DDMNs on fresh porcine ear skin shows, as observed by stereomicroscopic and confocal fluorescence microscopic analyses of the cross-sectioned tissue pieces, complete deposition followed by dissolution of the needles and diffusion of the PRNs in epidermis and dermis. Rats administered with a single dose of PRN-loaded DDMNs show significantly increased epidermal thickness as compared to rats administered with control DDMNs (no PRN). Both the PRN-loaded DDMNs and the control DDMNs produce no skin irritation in rats. Graphical abstract