Mapping and annotating genomic loci to prioritize genes and implicate distinct polygenic adaptations for skin color.

Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color evolution and genetics in East Asians are understudied. We quantified skin color in 48,433 East Asians using image analysis and identified associated genetic variants and potential causal genes for skin color as well as their polygenic interplay with sun exposure. This genome-wide association study (GWAS) identified 12 known and 11 previously unreported loci and SNP-based heritability was 23-24%. Potential causal genes were determined through the identification of nonsynonymous variants, colocalization with gene expression in skin tissues, and expression levels in melanocytes. Genomic loci associated with pigmentation in East Asians substantially diverged from European populations, and we detected signatures of polygenic adaptation. This large GWAS for objectively quantified skin color in an East Asian population improves understanding of the genetic architecture and polygenic adaptation of skin color and prioritizes potential causal genes.

Enhancement of Efficacy of Retinoids through Enhancing Retinoid-Induced RAR Activity and Inhibiting Hydroxylation of Retinoic Acid, and Its Clinical Efficacy on Photo-Aging.

Retinoids, one of the most robust bioactive materials, have been widely used to improve various dermatological and pathological conditions. The body has an endogenous mechanism that modulates the exogenous retinoid above physiological concentrations, which limits the bioavailability or pharmacological efficacy of retinoids. Considering that most retinoids trigger extensive irritation in users, it is necessary to enhance the pharmacological efficacy of retinoids, thereby achieving a higher efficacy at a lower dosage. Here, we present approaches for enhancing the efficacy of retinol by enhancing retinoid-induced RAR gamma (RAR-γ) activity and inhibiting the hydroxylation of retinoic acid. Using both in vitro and ex vivo experiments, retinoid boosters were demonstrated to enhance pharmacological efficacy. A small pilot study was conducted to investigate the efficacy for improvement of facial wrinkles, whose results revealed that these boosters could enhance the pharmacological efficacy of topical applications of both retinol and retinoic acid for cosmetic use. These results promote not only a higher compliance among retinoids users, but also provide significant insights into the mechanisms underlying the action of retinoids.

Sugar-Triggered Burst Drug Releasing Poly-Lactic Acid (PLA) Microneedles and Its Fabrication Based on Solvent-Casting Approach.

Microneedles have emerged as a novel transdermal delivery tool that enables the delivery of various products such as drugs, vaccines, or cosmetic ingredients. Although the demand for solid microneedles composed of biocompatible polymer is increasing, the manufacture of microneedles using poly-lactic acid (PLA) with rapid drug-releasing is yet to be established and the process is still in its infancy. Here, we propose a novel strategy for the fabrication of PLA solid microneedles which enable a drug to be burst-released based on a solvent-casting process. This approach offers extreme simplicity, broad geometric capability, cost-effectiveness, and scalability based on high fidelity-replicas. It was verified that microneedles of various heights (250-500 µm) could be fabricated with appropriate mechanical strength to penetrate the stratum corneum layer of skin. By adding sugar in the composition of PLA microneedle, it was observed that both hydrophilic and hydrophobic drugs can be rapidly released within 30 min. Our burst drug-releasing PLA microneedle having both characteristics of solid microneedle and soluble microneedle and its fabrication approach based on solvent-casting will contribute to getting microneedle technology close to commercialization and beyond existing technical limitations.

Novel human skin surface antimicrobial peptide quantification method using a skin patch test chamber: A pilot study.

INTRODUCTION: Antimicrobial peptides (AMPs) on the skin surface are related to the innate immunity of the skin in preventing external infection. Skin rinsing and tape stripping (TS) are acceptable methods for analyzing AMPs on the skin surface but have limitations, such as causing skin damage. In this study, we proposed a noninvasive method to measure AMPs on the skin surface with minimal skin damage. METHODS: Using the patch test assay, we aimed to analyze the skin surface human ß-defensin (hBDs) levels without damaging the skin barrier. The concentrations of hBDs on the skin surface were evaluated through the skin patch testing of 13 healthy subjects, and hBD-1 concentrations were compared with those obtained using the TS method in this proof-of-concept study. In addition, changes in skin physiology and concentration of hBDs under 1% sodium lauryl sulfate stimulation were monitored in 14 healthy subjects (8 young and 6 elderly subjects) for 150 h. RESULTS: The correlation between the two methods had a Pearson's coefficient of 0.640, and skin patch analysis led to a relatively less impaired barrier with no significant increase in transepidermal water loss after analysis. Age-specific comparisons suggested that higher skin surface hBD-2 concentrations were present in the young group as compared with the elderly group. Skin surface expression of hBD-2 after skin barrier disruption was also higher in the young group. CONCLUSION: Our findings show that skin patch analysis is a convenient method to analyze hBDs on the skin surface. hBDs are factors of innate immunity that can be used as an index to predict a decreased chemical immune response of skin due to aging.

Identifying patterns behind the changes in skin pores using 3-dimensional measurements and K-means clustering.

BACKGROUND: Skin pores are structural features of the skin, which tend to change as the skin ages. Since previous studies measured pores two-dimensionally, precise measurements using three-dimensional imaging were needed to comprehensively understand skin pores. This study aimed to determine the patterns behind the changes in skin pores during one's lifetime and to identify new characteristics of the pores in aged. MATERIALS AND METHODS: Skin surface profiles were measured three-dimensionally from the cheeks of 101 Korean women from February to March 2020 to analyze the exact state of their pores. The researchers performed K-means clustering to classify the skin pores, and topographical features of pores were analyzed as well. Statistical analyses were performed to verify the differences in the skin pore characteristics among clusters and the correlation between clusters and ages. RESULTS: Skin pores were classified into five groups based on size, density, and elongation. The skin conditions of the cluster groups were well correlated with aging, despite excluding age as a factor in pore classification. Adjacent skin pores tend to connect in the elderly. CONCLUSION: Skin pores become larger and longer over time. Skin pores connect together in the elderly, which might be related to wrinkle formation. This phenomenon strongly suggests skin pores as a characteristic of aging skin and as a potential target for anti-aging treatment.

GWAS Identifies Multiple Genetic Loci for Skin Color in Korean Women.

Human skin color is largely determined by genetic factors. Recent GWASs have reported several genetic variants associated with skin color, mostly in European and African populations. In this study, we performed GWAS in 17,019 Korean women to identify genetic variants associated with facial skin color, quantitatively measured as CIELAB color index. We identified variants in three, one, and six genomic loci associated with facial skin color index L∗, a∗, and b∗ values, respectively, and replicated the associations (combined analysis P-value < 5.0 × 10-8). The significant loci included variants in known genes (OCA2 rs74653330, BNC2 rs16935073, rs72620727 near KITLG, and SLC6A17 rs6689641) and to our knowledge previously unreported genes (SCARB1 rs10846744, SYN2 rs12629034, and LINC00486 rs6543678). This is GWAS to elucidate genetic variants of facial skin color in a Korean female population. Further functional characterizations of the investigated genes are warranted to elucidate their contribution to skin pigmentation-related traits.

Anti-Irritant Strategy against Retinol Based on the Genetic Analysis of Korean Population: A Genetically Guided Top-Down Approach.

Retinol, one of the most powerful cosmetic materials for anti-aging supported by a solid scientific background, exhibits a wide range of type and severity of irritation while showing limited user compliance. The lack of understanding of the mechanism of retinol-induced irritation has been the main hurdle in the development of anti-irritation strategies. Here, we identified 30 genetic markers related to the susceptibility to retinol-induced irritation in the Korean population. Based on the genetic analysis, a novel formula against retinol-induced irritation was developed, which mitigated the molecular pathogenesis-as indicated by the genetic markers-of the retinol-induced irritation. In human tests, this formula effectively decreased retinol-induced irritation. Furthermore, a polygenic risk score model for irritation was constructed and validated. Our comprehensive approach for the analysis of retinol-induced irritation will not only aid the development of anti-irritation strategies to ensure higher user compliance but also contribute to improving the current knowledge about the biological effects of retinoids.

Effect of the skincare product on facial skin microbial structure and biophysical parameters: A pilot study.

Daily use of cosmetics is known to affect the skin microbiome. This study aimed to determine the bacterial community structure and skin biophysical parameters following the daily application of a skincare product on the face. Twenty-five Korean women, who used the same skincare product for four weeks participated in the study. During this period, skin hydration, texture, sebum content, and pH were measured, and skin swab samples were collected on the cheeks. The microbiota was analyzed using the MiSeq system. Through these experiments, bacterial diversity in facial skin increased and the microbial community changed after four weeks of skincare product application. The relative abundance of Cutibacterium and Staphylococcus increased, significant changes in specific bacterial modules of the skin microbial network were observed, and skin hydration and texture improved. It was suggested that daily use of skincare products could affect the microbial structure of facial skin as well as the biophysical properties of the facial skin. These findings expand our understanding of the role of skincare products on the skin environment.

Validation of the elastic angle for quantitative and visible evaluation of skin elasticity in vivo.

BACKGROUND: Reduction in skin elasticity due to aging causes skin sagging and wrinkles. Although there are various objective and reliable techniques for measuring skin elasticity, it is difficult to obtain a visual representation of skin elasticity with them. Therefore, we developed a novel device, the Swing anglemeter, and analyzed its effectiveness for measuring skin elasticity of the cheek. MATERIALS AND METHODS: Forty-five healthy Korean women (age, 23-60 years) participated. The Swing anglemeter works by dropping a rubber ball on a subject's cheek, which draws a curve as it collides with the cheek. After recording the movement of the ball using the slow-motion function on a mobile phone, we defined the maximum angle at which the ball bounces off the skin as the elastic angle, using frame-by-frame video analysis. Changes in the elastic angle were assessed according to age, and correlation with the Ballistometer® results (Dia-stron Ltd., Andover, UK) was analyzed for validation. RESULTS: Elastic angles differed significantly (P < .001) according to age. A negative correlation was found between the elastic angle and age (r = -.799, P < .001). Compared with the Ballistometer® measurements, the elastic angle was negatively correlated with alpha (r = -.570, P < .001); it was positively correlated with the mean coefficient of restitution and area (r = .602, P < .001 and r = .535, P < .001, respectively). CONCLUSION: The elastic angle is a useful parameter for reflecting skin elasticity, both quantitatively and visually. Our method can help subjects understand their skin elasticity status. Therefore, we expect the device will be utilized in various fields within the cosmetic industry.

Synthesis of Retinol-Loaded Lipid Nanocarrier via Vacuum Emulsification to Improve Topical Skin Delivery.

Retinol has been widely used as an anti-wrinkle active ingredient in cosmetic fields. However, the oxidation of retinol by air was one of the critical problems for application in the skincare field. In this study, Retinol-loaded lipid nanocarriers were prepared via the vacuum emulsification method to increase the stability of retinol vulnerable to air and optimized encapsulation conditions and to increase the penetration efficiency into skin. Optimizing the components of lipid nanocarriers, gradients of carbon chain C8-22 using various lipid species which made the amorphous structure and enough spaces to load retinol inside the capsules were estimated from the lower enthalpy change and peak shift in DSC analysis. The vacuum-assisted lipid nanocarriers (VLN) could help suppress oxidation, which could have advantages to increase the thermal stability of retinol. The retinol-loaded VLN (VLN-ROL) had narrow size distribution under 0.3 PDI value, under 200 nm scaled particle size, and fully negative surface charge of about -50 mV for the electrostatic repulsion to avoid aggregation phenomenon among the lipid nanoparticles. It maintained 90% or more retinol concentration after 4 weeks of storage at 25, 40 and 50 °C and kept stable. The VLN-ROL-containing cream showed improved penetration efficiency applied to porcine skins compared to the commercial retinol 10S from BASF. The total amount of retinol into the skin of VLN-ROL (0.1% of retinol) was enhanced by about 2.2-fold (2.86 ± 0.23 µg) higher than that in 0.1% of bare retinol (about 1.29 ± 0.09 µg). In addition, applied on a 3D Human skin model, the epidermal thickness and the relative percentage of dermal collagen area effectively increased compared to the control and retinol, respectively. Additionally, the level of secreted IL-1α was lower and epidermal damage was weaker than commercial product A. This retinol-loaded lipid nanocarrier could be a potentially superior material for cosmetics and biomedical research.

Relationship between lip skin biophysical and biochemical characteristics with corneocyte unevenness ratio as a new parameter to assess the severity of lip scaling.

OBJECTIVE: Lip skin dryness and chapping are major concerns related to lip skin care in many populations. The distinctive features of lip skin, such as the low water-holding capacity and weak skin barrier, are strongly associated with these problems; however, few studies have examined lip skin characteristics and the mechanisms underlying these issues. This study was conducted to identify the biophysical properties of dry lip skin and molecular targets affecting lip skin physiology. METHODS: Skin hydration, transepidermal water loss and lip skin scaling were evaluated in 40 female subjects. Skin scaling was assessed as a percentage area divided into five categories (G0, G1, G2, G3 and G4) according to the thickness level of tape-stripped corneocytes. The activities and amounts of proteases, cathepsin D and bleomycin hydrolase were measured as markers for the desquamation process and skin hydration, respectively. RESULTS: Skin hydration showed a significantly positive correlation with the percentage area of evenly thin corneocytes (G0) and negative correlations with the percentage areas of slightly thick to severely thick corneocytes (G1-G4). The corneocyte unevenness ratio (CUR) was calculated by dividing the sum of the G1, G2, G3 and G4 values with the G0 value. The CUR was significantly negatively correlated with skin hydration, suggesting that CUR is a new parameter representing the severity of lip scaling. Subjects with lower hydration and higher CUR had higher bleomycin hydrolase activity and lower cathepsin D activity, respectively, than subjects with higher hydration and lower CUR. CONCLUSION: Our study revealed a correlation between lip skin hydration and severity of lip scaling and verified the association of protease activity with the hydration and chapping state of lip skin. These observations provide a basis for further studies of the persistent problem of lip skin dryness and chapping.

OBJECTIF: La sécheresse et la gerçure de la peau des lèvres sont des préoccupations majeures liées aux soins de la peau des lèvres chez de nombreuses populations. Les caractéristiques distinctives de la peau des lèvres, telles que la faible capacité de rétention d'eau et la faible barrière cutanée, sont fortement associées à ces problèmes ; cependant, peu d'études ont examiné les caractéristiques de la peau des lèvres et les mécanismes sous-jacents à ces problèmes. Cette étude a été menée dans le but d'identifier les propriétés biophysiques de la peau sèche des lèvres et les cibles moléculaires affectant la physiologie de la peau des lèvres. MÉTHODES: L'hydratation cutanée, la perte d'eau transépidermique et la desquamation de la peau des lèvres ont été évaluées chez 40 sujets de sexe féminin. La desquamation cutanée a été évaluée en tant que pourcentage de surface, divisée en cinq catégories (G0, G1, G2, G3 et G4) en fonction du niveau d'épaisseur des cornocytes sur la bande adhésive. Les activités et quantités des protéases, de la cathepsine D et de la bléomycine hydrolase ont été mesurées comme marqueurs du processus de desquamation et de l'hydratation cutanée, respectivement. RÉSULTATS: L'hydratation cutanée a montré une corrélation significativement positive avec le pourcentage de surface avec cornocytes uniformément minces (G0), et des corrélations négatives avec les pourcentages de surface avec cornocytes légèrement épais à très épais (G1-G4). Le rapport d'irrégularité des cornocytes (Corneocyte Unevenness Ratio, CUR) a été calculé en divisant la somme des valeurs de G1, G2, G3 et G4 par la valeur de G0. Le CUR était significativement corrélé négativement avec l'hydratation de la peau, ce qui suggère que le CUR est un nouveau paramètre représentant la gravité de la desquamation des lèvres. Les sujets avec une hydratation plus faible et un CUR plus élevé présentaient une activité de la bléomycine hydrolase plus élevée et une activité de la cathepsine D plus faible, respectivement, par rapport aux sujets avec une hydratation plus élevée et un CUR plus faible. CONCLUSION: Notre étude a révélé une corrélation entre l'hydratation de la peau des lèvres et la gravité de la desquamation des lèvres, et a vérifié l'association de l'activité de la protéase avec l'état d'hydratation et de gerçure de la peau des lèvres. Ces observations fournissent une base pour d'autres études sur le problème persistant de la sécheresse et de la gerçure de la peau des lèvres.

Development of the facial glycation imaging system for in situ human face skin glycation index measurement.

BACKGROUND: The accumulation of advanced glycation end products has been proposed as a causative agent of skin aging, but there are no conventional devices for quantifying advanced glycation end-product accumulation in facial skin. AIMS: This study aimed to develop a convenient and accurate in situ advanced glycation end-product measurement system for the human face. METHODS: We developed a facial glycation imaging system, which consisted of illumination (white light-emitting diode, ultraviolet light-emitting diode) and image acquisition modules to capture face images. Advanced glycation end product-related autofluorescence and total skin reflectance were calculated to obtain the skin glycation index using an image analysis algorithm. Correlations between the skin glycation index and facial skin elasticity and age were examined in 36 healthy Korean women. RESULTS: The facial glycation imaging system was validated against a volar forearm skin autofluorescence measurement device, that is, the AGE Reader mu, with forearm skin glycation index (R = 0.64, P < .01). Cheek elasticity was negatively correlated with cheek skin glycation index (R = -0.56, R = -0.57, and R = -0.61, P < .01 for R2, R5, and R7, respectively). Age was significantly correlated with forearm skin glycation index (R = 0.44, P < .01) and cheek skin glycation index (R = 0.48, P < .01). CONCLUSION: We successfully developed a novel in situ facial skin glycation index measurement device. Our convenient and accurate system enables in situ skin glycation index monitoring for skin aging studies such as those on anti-glycation cosmetics.

Influence of quarantine mask use on skin characteristics: One of the changes in our life caused by the COVID-19 pandemic.

BACKGROUND: The influence of various environmental factors on skin properties is well known. However, there is a lack of research into the effect of quarantine masks on skin properties, even though the use of masks has significantly increased after the COVID-19 outbreak. Therefore, this study aimed to investigate the influence of mask use on skin properties. MATERIALS AND METHODS: Twenty subjects were enrolled in this study. The subjects used approved quarantine masks for 6 hours a day for 2 weeks. We measured eight skin biophysical parameters: temperature, redness, pore volume, texture, elasticity, trans-epidermal water loss (TEWL), sebum content, and pH, and evaluated acne lesions before and after using quarantine masks. The evaluation was performed on the mask-wearing area of the face. RESULTS: Skin temperature, redness, and TEWL increased significantly after a 6-hour mask use, while the sebum content increased marginally. Skin elasticity was reduced by the use of masks over 1 and 2 weeks, whereas the pore volume and the number of acne lesions increased after a 2-week mask use. The skin changes caused by mask use showed sex-based differences in the skin elasticity (after 6 hours), redness, and roughness (after 2 weeks). CONCLUSIONS: The use of quarantine masks causes a change in the skin temperature, redness, and TEWL in the short term and in skin elasticity, pores, and acne in the long term. This study revealed that prolonged mask use could have negative effects on the skin.

Comparative analysis of skin characteristics evaluation by a dermatologist and the Janus-III measurement system.

BACKGROUND: The Janus-III measurement system evaluates the overall skin characteristics such as skin pore, wrinkle, sebum, porphyrin, skin pigmentation, and skin color using high-resolution facial images. The values are measured from five different facial areas, namely, the forehead, nose, corner of/skin below the eyes, and cheeks. Owing to its convenience and diverse measuring characteristics, Janus-III has been widely used in skin research and the cosmetic industry in Korea. In our previous study, we revealed the consistency and reliability of the system with repeatedly measured values. Its measuring performance was investigated statistically, but to make it more reliable for academic skin research, additional verification by a professional dermatologist is needed. MATERIALS AND METHODS: In this study, we conducted comparative analysis of three skin characteristics (pigmented spot, skin color, and eye wrinkle) by a dermatologist and the Janus-III measurement system. We utilized 330 image data that were cropped from the whole facial images of 330 different participants to avoid correlation among the three measuring items. Pearson's correlation coefficient exhibited similar patterns between the system and the dermatologist's findings. RESULTS: The main finding of our study was that the measured value of skin characteristics by the Janus-III system showed clear correlation with the values evaluated by a dermatologist, especially in a pigmented spot. CONCLUSION: Therefore, it would be a plausible idea to consider the Janus-III system for specialized research of skin characteristics even with a small sample size.

GWAS Analysis of 17,019 Korean Women Identifies the Variants Associated with Facial Pigmented Spots.

Variation in skin pigmentation can be affected by both environmental factors and intrinsic factors such as age, gender, and genetic variation. Recent GWASs revealed that genetic variants of genes functionally related to a pigmentation pathway were associated with skin pigmentary traits. However, these GWASs focused on populations with European ancestry, and only a few studies have been performed on Asian populations, limiting our understanding of the genetic basis of skin pigmentary traits in Asians. To evaluate the genetic variants associated with facial pigmented spots, we conducted a GWAS analysis of objectively measured facial pigmented spots in 17,019 Korean women. This large-scale GWAS identified several genomic loci that were significantly associated with facial pigmented spots (five previously reported loci and two previously unreported loci, to our knowledge), which were detected by UV light: BNC2 at 9p22 (rs16935073; P-value = 2.11 × 10-46), PPARGC1B at 5q32 (rs32579; P-value = 9.04 × 10-42), 10q26 (rs11198112; P-value = 9.66 × 10-38), MC1R at 16q24 (rs2228479; P-value = 6.62 × 10-21), lnc01877 at 2q33 (rs12693889; P-value = 1.59 × 10-11), CDKN2B-AS1 at 9p21 (rs643319; P-value = 7.76 × 10-9), and MFSD12 at 19p13 (rs2240751; P-value = 9.70 × 10-9). Further functional characterization of the candidate genes needs to be done to fully evaluate their contribution to facial pigmented spots.

Biophysical characteristics of dandruff-affected scalp categorized on the basis of sebum levels.

BACKGROUND: Various sebum levels can be detected in dandruff-affected scalps. However, few studies have compared the biophysical characteristics of dandruff scalps categorized based on sebum levels. AIMS: To investigate and compare the biophysical characteristics of dandruff-affected scalps categorized based on sebum levels. METHODS: Fifty-four Korean women with dandruff and 30 healthy Korean women underwent physiological measurements, including evaluation of sebum and hydration levels, pH, and transepidermal water loss (TEWL) in the scalp. The levels of the biomarkers of interleukin-8 (IL-8) and kallikrein 5 (KLK5) and corneodesmosomes were investigated in the stratum corneum (SC) of the scalp. RESULTS: Dandruff was categorized as dry (low-sebum, n = 25) or oily (high-sebum, n = 29) based on a sebum cutoff level of 97.82 µg/cm2 . Both dry and oily dandruff-affected scalps showed significantly decreased hydration levels and increased pH and TEWL compared with healthy subjects, with hydration levels being lower in dry dandruff-affected scalps. IL-8 expression was significantly increased in the oily dandruff-affected scalp. In addition, both dry and oily dandruff-affected scalps showed significantly increased KLK5 levels in the SC, with the levels being higher in oily dandruff-affected scalps. Altered distribution of corneodesmosomes, present on the entire surface area of the corneocytes, was notable in oily dandruff-affected scalps. CONCLUSION: The biophysical characteristics of the two types of dandruff represent the influence of different characteristics, including hydration levels, expression of IL-8 and KLK5, and corneodesmosome distribution. Thus, strategies to reduce dandruff levels should differ according to sebum levels.

Opioid-free anesthesia with a mixture of dexmedetomidine, ketamine, and lidocaine in one syringe for surgery in obese patients.

Recently, there has been a trend toward minimizing opioid use in obese patients to prevent opioid-related postoperative complications. Moreover, the use of opioid-free anesthesia has received growing interest. This case series reports the use of simple opioid-free anesthesia consisting of a mixture of dexmedetomidine, ketamine, and lidocaine in an obese male patient undergoing laparoscopic bariatric surgery and an obese pregnant woman undergoing cesarean section. These cases indicate that opioid-free anesthesia can be safely administered to obese patients and provides effective pain control without any postoperative adverse outcomes.

A Semi-Dissolving Microneedle Patch Incorporating TEMPO-Oxidized Bacterial Cellulose Nanofibers for Enhanced Transdermal Delivery.

Although dissolving microneedles have garnered considerable attention as transdermal delivery tools, insufficient drug loading remains a challenge owing to their small dimension. Herein, we report a one-step process of synthesizing semi-dissolving microneedle (SDMN) patches that enable effective transdermal drug delivery without loading drugs themselves by introducing TEMPO-oxidized bacterial cellulose nanofibers (TOBCNs), which are well dispersed, while retaining their unique properties in the aqueous phase. The SDMN patch fabricated by the micro-molding of a TOBCN/hydrophilic biopolymer mixture had a two-layer structure comprising a water-soluble needle layer and a TOBCN-containing insoluble backing layer. Moreover, the SDMN patch, which had a hole in the backing layer where TOBCNs are distributed uniformly, could offer novel advantages for the delivery of large quantities of active ingredients. In vitro permeation analysis confirmed that TOBCNs with high water absorption capacity could serve as drug reservoirs. Upon SDMN insertion and the application of drug aqueous solution through the drug inlet hole, the TOBCNs rapidly absorbed the solution and supplied it to the needle layer. Simultaneously, the needle layer dissolved in body fluids and the drug solution to form micro-channels, which enabled the delivery of larger quantities of drugs to the skin compared to that enabled by solution application alone.