Delivery and Diffusion of Retinal in Dermis and Epidermis Through The Combination of Prodrug Nanoparticles and Detachable Dissolvable Microneedles

To minimize fast chemical degradation of retinal, we convert this aldehyde into proretinal nanoparticles (PRNs) by forming retinylidene moieties on chitosan and allowing the grafted polymers to assemble into nanoparticles, and then load the obtained PRNs into detachable microneedles made of 1:1 (by weight) hyaluronic acid/maltose. An embedment of the PRNs in the solid matrix of microneedles helps improving chemical stability of the grafted retinal; the loaded device can be kept at 25 °C for three months (longest time experimented) with less than 30% degradation of the retinylidene moieties. The presence PRNs in the hyaluronic acid-maltose matrix also help improving mechanical strength of the needles. Administration of PRN-loaded detachable microneedles on fresh porcine ear skin results in complete deposition of an array of microneedles in the skin tissue at the dept that spans both epidermis and dermis, as observed by stereomicroscopic and confocal fluorescence microscopic analyses of the cross-sectioned tissue pieces. Obvious diffusion of the PRNs from the originally embedded site of the needles in the skin tissue to the nearby location can be observed, and even distribution in the tissue is reached at 4 h post administration. Rats administered with single dose of PRN-loaded microneedles show significant increased epidermal thickness as compared to rats administered with unloaded microneedles. Both PRN-loaded microneedles and unloaded microneedles produce no skin irritation in rats.