Safety Evaluation of Stamp Type Digital Microneedle Devices in Hairless Mice

BACKGROUND: Microneedles provide a minimally invasive means to transport molecules into the skin. A number of specific strategies have been employed to use microneedles for transdermal delivery. OBJECTIVE: The purpose of this study was to investigate the safety of two new digital microneedle devices (Digital Hand(R) and Digital Pro(R); Bomtech Electronics Co., Ltd., Seoul, Korea) for the perforation of skin in skin-hairless-1 mice. This device replaces conventional needles and is designed specifically for intradermal delivery. METHODS: We used two newly developed digital microneedle devices to perforate the skin of skin-hairless-1 mice. We conducted a comparative study of the two digital microneedle devices and DTS(R) (Disk type-microneedle Therapy System; DTS lab., Seoul, Korea). To evaluate skin stability, we performed visual and dermatoscopic inspections, measurements of transepidermal water loss, and biopsies. RESULTS: The two novel digital microneedle devices did not induce significant abnormalities of the skin on visual or dermatoscopic inspection, regardless of needle size (0.25~2.0 mm). No significant histopathological changes, such as inflammatory cell infiltration, desquamation of the stratum corneum, or disruption of the basal layer, were observed. The digital microneedle devices and microneedle therapy system produced similar results on measures of skin stability. CONCLUSION: These two novel digital microneedle devices are safe transdermal drug delivery systems.

The Evaluation of Skin Safety and Skin Cell Toxicity for Scutellaria baicalensis Georgi Extract according to Extraction Conditions / 대한피부과학회지

BACKGROUND: Scutellaria baicalensis Georgi extract is used as a traditional herbal medicine. The efficacy of Scutellaria baicalensis Georgi extract is known for antioxidative activity, antiinflammation effect, antibacterial effect, inhibitory effect of melanin synthesis, sun protection effect, antiallergy effect, and etc. OBJECTIVE: We confirmed the cell viability or inhibitory effect of melanin synthesis in HaCaT (human keratinocyte cell line) and B16F10 (murine melanoma cell line) cells and the skin safety test through a clinical test (dermal irritation study) for Scutellaria baicalensis Georgi extract, according to the extraction methods. METHODS: We checked the cell viability, using MTT assay and inhibitory effect of melanin synthesis in B16F10 cells or HaCaT cells for thirty one Scutellaria baicalensis Georgi extract, according to the extraction methods. Then, we evaluated the skin safety for selected eight Scutellaria baicalensis Georgi extract through a primary dermal irritation test. RESULTS: Among the thirty one Scutellaria baicalensis Georgi extracts, according to the extraction methods, we selected eight Scutellaria baicalensis Georgi extracts that were not detected with cell toxicity in HaCaT cells and B16F10 cells, and could have inhibited the melanin synthesis in B16F10 cells. The selected eight Scutellaria baicalensis Georgi extracts identified the skin safety through a primary dermal irritation test. CONCLUSION: We expect clinical trials for whitening efficacy based on inhibitory effect of melanin synthesis and human skin safety for Scutellaria baicalensis Georgi extracts.

A Study of Potential Application of Rubus coreanus Miquel Extract for Seborrheic Dermatitis Treatment / 대한의진균학회지

BACKGROUND: Seborrheic dermatitis is chronic relapsing inflammatory skin disorder. Bokbunja (Rubus coreanus Miquel) is a wild berry to Rosaceae genus and also known to have an anti-inflammation effect. OBJECTIVE: We were to determine the effect of Rubus coreanus Miquel extract for seborrheic dermatitis in vivo and in vitro. METHODS: Seven patients with mild seborrheic dermatitis were enrolled in this study. PCR and culture were performed to identify subtypes of six Malassezia species (M. restricta, M. globosa, M. furfur, M. slooffiae, M. sympodialis, M. obtusa). Topical application of Rubus coreanus Miquel Extract was applied twice daily for 2 weeks. Clinical improvement and safety assessment were performed initially and 2 weeks later. Minimum inhibitory concentration (MIC) was evaluated on Malassezia globosa comparing with ketoconazole and itraconazole. Sebum production was also checked prior the experiment and 2 weeks later. RESULTS: Five of seven patients showed improvement. No significant adverse effects were found during the clinical trial. Mild dryness was reported in 2 patients but they resolved spontaneously without any treatment. Rubus coreanus Miquel Extract didn't show antimicrobial effect to Malassezia globosa. However, Rubus coreanus Miquel Extract showed anti-inflammatory effect. CONCLUSION: In this study, we were verified that Rubus coreanus Miquel Extract can be applied for seborrheic dermatitis treatment. And this action mechanism is not related with antimicrobial effect.

Anti-inflammatory and Anti-oxidant Effects of Sophora flavescens Root Extraction in Lipopolysaccharide-activated Raw 264.7 Cells / 대한의진균학회지

BACKGROUND: The macrophages activated by lipopolisaccharide produce numerous molecules and proteins, such as tumor necrotic factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and free radicals, associated with inflammation. The response was occurred by intracellular cascaded, NF-kappaB pathway. So, the regulation of this pathway is very important in control of inflammation. OBJECTIVE: In this study, the anti-inflammatory and anti-oxidant effects of Sophora flavescens that is used empirically in oriental medicine and folk remedy were evaluated and the mechanism of the effects was studied. METHODS: By using the root extracts of Sophora flavescens, we performed experiment in LPS and interferon-gamma (IFN-gamma)-activated Raw 264.7 cells. We measured the production of NO, PGE2 and expression of iNOS and COX-2 in activated Raw 264.7 cells with Sophora flavescens root extract. Also, we tested anti-oxidant effect of Sophora flavescens root extracts by ELISA kit in activated Raw 264.7 cells, and the free radical scavenging effect of material itself by DPPH assay. RESULTS: The Sophora flavescens root extracts decreased the production of NO (p<0.001) and PGE2 (p<0.01) in Raw 264.7 cells activated by LPS and IFN-gamma. The expression of proteins, iNOS and COX-2, suppressed along with the elevated concentration of Sophora flavescens root extracts. The result of DPPH assay was that the test material itself had scavenging effect for free radical (p<0.001). And the antioxidant activity in activated Raw 264.7 cells was increased with the level of the Sophora flavescens root extracts (p<0.05). CONCLUSION: The Sophora flavescens root extracts suppressed the production of NO and PGE2 through the decreased expression of iNOS and COX-2. And the Sophora flavescens root extracts had the scavenging effect about free radicals itself and increased the antioxidant activity in activated macrophages.

Optimal Culture Condition for Antifungal Susceptibility Tests of Malassezia globosa / 대한의진균학회지

BACKGROUND: Although numerous culture conditions for Malassezia species were suggested, there were not so many objective evaluation articles in the literature. OBJECTIVES: We examined the various culture conditions for Malassezia globosa. METHODS: Malassezia globosa culture conditions were assessed by Dixon's agar, modified Leeming-Notman medium in diverse oil content and temperature conditions. RESULTS: Maximum growth rate of Malassezia globosa was achieved at 3% olive oil. The optimal temperatures for the maximal growth of M. globosa were observed at 32~34degrees C. CONCLUSION: In this study, we established the optimal culture condition for M. globosa, and confirmed its excellent utility for the antifungal susceptibility tests for M. globosa and M. restricta. Our results can help the investigators plan to do the prospective researches involving Malassezia species, such as the susceptibility test for newly developed antifungal agents.