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.

Detachable dissolvable microneedles: intra-epidermal and intradermal diffusion, effect on skin surface, and application in hyperpigmentation treatment.

Delivering bioactive compounds into skin tissue has long been a challenge. Using ex vivo porcine and rat skins, here we demonstrate that a detachable dissolvable microneedle (DDMN) array, a special dissolvable microneedle that allows needle detachment from the base within 2 min post administration, can effectively embed a model compound into epidermis and dermis. Diffusion of the compound from the needle embedding sites to the nearby skin tissue is demonstrated at various post administration periods. The relationship between the time that a conventional dissolvable microneedle array is left on skin without needle detachment from the base and the degree of skin surface abrasion at each microneedle penetration spot is also demonstrated on skin of human volunteers. Co-loading glutathione with vitamin C (vitC) can stabilize vitC in the DDMN. DDMN loaded with vitC and glutathione can help erasing post-acne-hyperpigmentation spots.

Solid Composite Material for Delivering Viable Cells into Skin Tissues via Detachable Dissolvable Microneedles.

Delivering cells to desired locations in the body is needed for disease treatments, tissue repairs, and various scientific investigations such as animal models for drug development. Here, we report the solid composite material that when embedded with viable cells, can temporarily keep cells alive. Using the material, we also show the fabrication of detachable dissolvable microneedles (DMNs) that can instantly deliver viable cells into skin tissue. B16-F10-murine-melanoma (B16-F10) and human-embryonic-kidney-293T (HEK293T) cells embedded in the solid matrix of the hyaluronic/polyvinylpyrolidone/maltose (HA/PVP/maltose) mixture show 50.6 ± 12.0 and 71.0 ± 5.96% survivals, respectively, when kept at 4 °C for 24 h. Detachable DMNs made of the HA/PVP/maltose mixture and loaded with B16-F10-cells were constructed, and the obtained DMN patches could detach the cell-loaded needles into the skin within 1 min of patch application. In vivo intradermal tumorgrafting mice with the DMNs containing 800 cells of B16-F10 developed tumors 10 times bigger in volume than tumors induced by hypodermic needle injection of suspension containing 100,000 cells. We anticipate this work to be a starting point for viable cell encapsulation in the solid matrix and viable cell delivery via DMNs.