Non-invasive Microneedle Application Increases Ceramide and Natural Moisturizing Factors in a Reconstructed Human Skin Model.

Recently, microneedling as a cosmetic product has attracted attention as one way to improve skin barrier function and moisturizing function to reduce wrinkle formation. However, some cases of erythema and edema have been reported as side effects. In order to develop safer microneedle cosmetics, we investigated whether microneedles can improve skin barrier function and moisturizing function even when applied in a non-invasive manner that does not penetrate the stratum corneum. We established the condition of non-penetrating microneedle application on reconstructed human full-thickness skin models and examined the effect on the skin models when microneedles were applied under this condition. Microneedle application increased the gene expression of serine palmitoyltransferase long chain base subunit (SPTLC) 3, filaggrin, and transglutaminase 1. The amount of ceramide produced by SPTLC was also increased by microneedle application. Gene expression of filaggrin-degrading enzymes and the amount of free amino acids, a product of filaggrin degradation, were also increased by microneedling. These results suggest that non-invasive microneedle application can improve skin barrier function and moisturizing function by increasing the amount of ceramide and natural moisturizing factors.

Skin application of ketoprofen systemically suppresses contact hypersensitivity by inducing CD4(+) CD25(+) regulatory T cells.

BACKGROUND: Ketoprofen (KP) is a widely used nonsteroidal anti-inflammatory drug that inhibits prostaglandin biosynthesis. We have previously shown that topical KP treatment at the sensitizing site inhibits the development of contact hypersensitivity (CHS) to picryl chloride (PCl). OBJECTIVE: We investigated the mechanism underlying the KP-induced immunosuppression of CHS by application of KP. METHODS: We analyzed the CHS responses to the non-sensitizing site and subsequent sensitization with PCl, and by transfer of the draining lymph node cells (LNCs) from KP-tolerated mice to recipient mice. Changes in the Foxp3 expression of LNCs from KP-phototreated skin were also examined by real-time PCR. RESULTS: Topical application of KP to not only the sensitizing but also non-sensitizing site suppressed CHS response. The immunosuppression was transferred with LNCs from mice treated with PCl plus KP, but not from mice treated oxazolone plus KP. In this transfer study, the CD4(+) CD25(+) subset of LNCs exerted the suppressive effect, while CD25(+) cell-depleted LNCs lost the inhibitory ability. CTLA-4 blocking with a specific antibody, but not IL-10 blocking, abrogated the activity of CD4(+) CD25(+) cells. Moreover, Foxp3 mRNA expression was remarkably increased in LNCs from PCl and KP-treated mice. CONCLUSION: The immunosuppression of CHS by topical application of KP is systemic and haptein-specific. Treg cells play an important role in the suppressive effect by KP.

Serious photocontact dermatitis induced by topical ketoprofen depends on the formulation.

BACKGROUND: Topical administration of ketoprofen to treat local subcutaneous pain significantly reduces gastrointestinal and cardiovascular adverse effects associated with oral delivery. However, this benefit must be weighed against the risk of photosensitisation/phototoxicity. OBJECTIVE: To substantiate the safety and efficacy of topical ketoprofen delivery from a patch. METHODS: Experiments were performed, and published information analysed, (a) to confirm the superior skin permeability and pharmacological activity of ketoprofen, and (b) to demonstrate the lower incidence of ketoprofen photosensitisation/phototoxicity when delivered from a topical patch. RESULTS: Ketoprofen's photodegradation products were more photoallergic than the drug itself. The period post-ketoprofen treatment that skin should be protected from UV radiation (while the drug is cleared from the application site) was estimated. CONCLUSIONS: Photosensitisation to ketoprofen can be mitigated by a patch formulation, which protects the drug from direct UV exposure during skin application, and reduces the formation of even more photoallergic photodegradation products.

Addition of UVA-absorber butyl methoxy dibenzoylmethane to topical ketoprofen formulation reduces ketoprofen-photoallergic reaction.

Topical application of ketoprofen (KP) clinically evokes the allergic type of photocontact dermatitis. To avoid this adverse reaction, we investigated the beneficial effect of each ultraviolet (UV) filter that was included in topical ketoprofen formulation. We first tested the inhibitory effects of four UVA filters by a modified local lymph node assay following KP application on the mouse skin and UVA irradiation on the same site. In this assessment, butyl methoxy dibenzoylmethane (BMDBM), when included in KP application, exerted the most effective inhibitory effect on stimulation with KP and UVA. We manufactured topical patch and gel KP applicants containing BMDBM, which retained KP penetration through the skin and KP stability toward UVA. The ability of BMDBM in these formulations to inhibit KP photosensitivity was evaluated by a modified adjuvant and strip method in guinea pigs, and the photoallergic reactions induced by the BMDBM-containing KP applicants were lower than the non-containing ones. It is known that KP has a cross-reactivity with benzophenone upon UVA exposure, but such a photocross-reactivity of BMDBM with KP was not observed in a mouse ear swelling model. The anti-inflammatory effect of the BMDBM-containing KP patch applicant was comparable to the non-containing one. These results suggest that the addition of BMDBM into KP topical formulations is efficacious for inhibition of KP photocontact dermatitis.