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Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article. [ABSTRACT FROM AUTHOR]

Food contamination by pathogenic microorganisms has been a serious public health problem and a cause of huge economic losses worldwide. Foodborne pathogenic Escherichia coli ( E. coli) contamination, such as that with E. coli O157 and O104, is very common, even in developed countries. Bacterial contamination may occur during any of the steps in the farm-to-table continuum from environmental, animal, or human sources and cause foodborne illness. To understand the causes of the foodborne outbreaks by E. coli and food-contamination prevention measures, we collected and investigated the past 10 years' worldwide reports of foodborne E. coli contamination cases. In the first half of this review article, we introduce the infection and symptoms of five major foodborne diarrheagenic E. coli pathotypes: enteropathogenic E. coli (EPEC), Shiga toxin-producing E. coli/enterohemorrhagic E. coli (STEC/EHEC), Shigella/enteroinvasive E. coli (EIEC), enteroaggregative E. coli (EAEC), and enterotoxigenic E. coli (ETEC). In the second half of this review article, we introduce the foodborne outbreak cases caused by E. coli in natural foods and food products. Finally, we discuss current developments that can be applied to control and prevent bacterial food contamination. [ABSTRACT FROM AUTHOR]

In this study, acid and light dual- stimuli-responsive amphiphilic AB-type methoxy poly(ethylene glycol)-acetal-ONB-poly(4-substituted-ε-caprolactone) (MPEG-a-ONB-PXCL) diblock copolymers were synthesized using ring-opening polymerization and nucleophilic substitution reactions. The prepared copolymer features an acid-cleavable acetal group and photocleavable o-nitrobenzyl linkage between the hydrophilic MPEG and hydrophobic PXCL blocks. The design enables the diblock copolymers to respond to both acid and ultraviolet (UV) light while ensuring the minimum number of stimuli-reactive moieties in the copolymer structure. The disruption of the copolymeric micelles in aqueous solution was examined under the action of pH or UV light alone or under the combined stimulation pH and UV light. Under the combined stimulation of UV irradiation and pH, the micellar nanoparticles could dissociate; therefore, the loaded molecules could be released from the assemblies more efficiently than under either stimulus alone. The nanoparticles exhibited nonsignificant toxicity against human cervical cancer (HeLa) cells at concentrations ≤300 μg mL. Doxorubicin (DOX)-loaded micelles facilitated the uptake of DOX by the HeLa cells at the initial stage. The dual stimuli-cleavable polymeric micelles show promising potential as new nanocarrier for precisely controlled release of encapsulated drug. [ABSTRACT FROM AUTHOR]

Phytochemicals present in vegetables, fruits, and herbs are believed to reduce the risk of several major diseases including cardiovascular or neurodegenerative disorders. The roots of the fern Helminthostachys zeylanica (L.) Hook. (Ophioglossaceae) have been used for centuries in the treatment of inflammation and as a folk medicine in several countries. The plant has been shown to possess an array of medicinal properties, including antioxidants and anti-inflammatory activities. Moreover, a rising level of matrix metalloproteinase-9 (MMP-9) has been found in blood fluid of these patients suffering from brain inflammatory diseases, which may be considered an inflammatory biomarker in several inflammatory diseases including the central nervous system (CNS) inflammation. Previously, we have demonstrated the signaling mechanisms of bradykinin (BK)-induced MMP-9 expression in brain astrocytes. Herein, we evaluate the effects of H. zeylanica extracts on BK-induced MMP-9 expression in brain astrocytes and its influencing mechanism. The results showed that H. zeylanica extracts, including E0, E1, and E2 significantly reduce MMP-9 induced by BK in brain astrocytes (RBA-1 cells). These H. zeylanica extracts can inhibit BK-stimulated phosphorylation of c-Src, Pyk2, and PKC(α/δ). Moreover, BK-stimulated NADPH oxidase (Nox)-derived reactive oxygen species (ROS) generation has also been attenuated by pretreatment with these extracts, suggesting that the H. zeylanica extracts have an antioxidative activity. We further demonstrated that the H. zeylanica extracts blocked activation of MAPKs (e.g., ERK1/2 and p38 MAPK) by BK. These data indicated that the H. zeylanica extracts may be has anti-inflammatory activity by reducing BK-induced ROS-dependent MMP-9 expression via these related pathways in brain astrocytes. [ABSTRACT FROM AUTHOR]

Purpose: As a continuing effort to elucidate the impact of structure modification upon cutaneous absorption behavior, we attempted to assess the skin permeation of magnolol by methylation and acetylation. Methods: Diacetylmagnolol and 2- O-acetyl-2′- O-methylmagnolol (AMM) were designed and synthesized in this study. The anti-inflammatory activity against stimulated neutrophils and keratinocytes was evaluated to check the bioactivity of the analogues. In vitro skin absorption was investigated using nude mouse and pig skin models at both equimolar and saturated doses. Results: Magnolol generally showed the strongest anti-inflammatory potential, followed by diacetylmagnolol and AMM. The antibacterial activity was observed for magnolol and diacetylmagnolol but not AMM. Diacetylmagnolol and AMM could be partly hydrolyzed to magnolol and 2- O-methylmagnolol after entering the skin. The hydrolysis rate of diacetylmagnolol was faster than that of AMM. The lipophilicity played a crucial role in cutaneous absorption, with AMM exhibiting the highest skin deposition. AMM accumulation within nude mouse skin was about 2.5-fold greater than that of magnolol and diacetylmagnolol. On the other hand, the transdermal penetration across the skin was lessened by methylation and esterification. This led to a superior skin targeting of AMM. Although the pharmacological activity of AMM was low, the high skin uptake and bioconversion into 2- O-methylmagnolol in the skin contributed to a greater therapeutic index (TI, skin deposition x inflammatory inhibition percentage) compared to the others. The accumulation of AMM in the hair follicles was 77.12 nmol/cm, which was significantly greater than that with magnolol (44.84 nmol/cm) and diacetylmagnolol (26.96 nmol/cm). The synthetic analogues were tolerable to the nude mouse skin. Conclusions: Based on the experimental results, we may suggest topically applied AMM as a potent and safe candidate for the treatment of cutaneous inflammation. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated. Methods: The morphology of the skin was examined by transmission electron microscopy (TEM), higher harmonic generation microscopy (HGM), and physiological factors. In vivo skin distribution of macromolecules was assessed by fluorescence and confocal microscopies. Results: RF thermolysis selectively created an array of micropores deep into the epidermis without significant removal of the stratum corneum (SC). With energy of 30 mJ, a pore depth of 35 μm was achieved. The bipolar RF resulted in a 3-fold increase of transepidermal water loss (TEWL) compared with intact skin. The respective skin accumulation and flux of the peptide with a molecular weight (MW) of 2335 Da was 3- and 23-fold greater for the RF-treated group than for the non-treatment group. RF enhanced skin accumulation of siRNAs with MW of 10 and 15 kDa by 6.2- and 2.6-fold, respectively. Cutaneous penetration of the macromolecules with an MW of at least 40 kDa could be accomplished by RF. Confocal microscopy imaging revealed that RF could effectively deliver the peptide up to at least a 74-μm depth. The penetration depth of siRNA by RF irradiation was about 50 μm. Conclusions: The novel RF device efficiently delivered macromolecules into the skin while reserving SC layers to support some barrier functions. In this work, for the first time the assistance of fractional RF on peptide and siRNA transport was demonstrated. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) exposure and menopause are known as the inducers of damage to the skin structure. The combination of these two factors accelerates the skin aging process. In this study, we aimed to evaluate the influence of UV and ovariectomy (OVX) on the permeation of drugs through the skin. The role of tight junctions (TJs) and adherens junctions (AJs) in the cutaneous absorption of extremely lipophilic permeants and macromolecules was explored. The OVX nude mouse underwent bilateral ovary removal. Both UVA and UVB were employed to irradiate the skin. The physiological and biochemical changes of the skin structure were examined with focus on transepidermal water loss (TEWL), skin color, immunohistochemistry, and mRNA levels of proteins. UVB and OVX increased TEWL, resulting in stratum corneum (SC) integrity disruption and dehydration. A hyperproliferative epidermis was produced by UVB. UVA caused a pale skin color tone due to keratinocyte apoptosis in the epidermis. E-cadherin and β-catenin showed a significant loss by both UVA and UVB. OVX downregulated the expression of filaggrin and involucrin. A further reduction was observed when UV and OVX were combined. The in vitro cutaneous absorption demonstrated that UV increased the skin permeation of tretinoin by about twofold. However, skin accumulation and flux of estradiol were not modified by photoaging. OVX basically revealed a negligible effect on altering the permeation of small permeants. OVX increased tretinoin uptake by the appendages from 1.36 to 3.52 μg/cm2. A synergistic effect on tretinoin follicular uptake enhancement was observed for combined UV and OVX. However, the intervention of OVX to photoaged skin resulted in less macromolecule (dextran, molecular weight = 4 kDa) accumulation in the skin reservoir because of retarded partitioning into dry skin. The in vivo percutaneous absorption of lipophilic dye examined by confocal microscopy had indicated that the SC was still important to controlling topical delivery, although the role of epidermal junctions could not be simply ignored. [ABSTRACT FROM AUTHOR]

Purpose: Here we report the development of quantiosomes, niosomes formed from Span 60, cholesterol, and quantum dots (QDs), for achieving sensitive bioimaging and anticancer drug delivery. Methods: The nanocarriers were further modified by incorporating soy phosphatidylcholine (SPC), polyethylene glycol (PEG), or cationic surfactant to display different efficiencies. Carboplatin was used as the model drug. The cellular uptake, cytotoxicity, and migration inhibition of quantiosomes for treating melanoma cells were described. Finally, intratumoral carboplatin accumulation and in-vivo bioimaging were examined. Results: The average diameters of quantiosomes ranged between 151 and 173 nm, depending on the composition selected. Approximately 50% of the drug was entrapped in quantiosomes. Electron microscopy confirmed the bilayer structure of quantiosomes and the presence of QDs in the vesicular surface. The nanodispersions showed a significant internalization into cells, especially the cationic formulations. Quantiosomes increased cytotoxicity against melanoma by 3 ~ 4-fold as compared to free carboplatin. In-vivo intratumoral administration demonstrated an increased drug depot in melanoma from 6 to 10 ng/mg by SPC-loaded and PEGylated quantiosomes relative to aqueous control. In-vivo fluorescence imaging showed that quantiosomes reduced leakage of QDs from melanoma. A fluorescence signal confined in tumors could be sustained for at least 24 h. Quantiosomes also exhibited a sensitive and prolonged fluorescence in ovarian tumors. Conclusion: Niosomes containing QDs and carboplatin as a multifunctional nanosystems provide a non-expensive and efficient strategy to prolong drug retention and fluorescence signal in tumors. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess impact of different vehicles for laser-assisted skin drug delivery. We also tried to uncover the mechanisms by which different vehicles affect laser-aided skin permeation. Methods: Full-surface ablative (conventional) and fractional lasers were used to irradiate nude mouse skin. Imiquimod and 5-aminolevulinic acid (ALA) were used as lipophilic and hydrophilic permeants. Vehicles employed included water with 40% polyethylene glycol 400 (PEG 400), propylene glycol (PG), and ethanol. Lipid nanoparticles were also utilized as carriers. Results: In vitro permeation profiles showed improvement in imiquimod flux with conventional laser (2.5 J/cm) producing a 12-, 9-, and 5-fold increase when loading imiquimod in 40% PEG400, PG, and ethanol, respectively, as compared with intact skin. Nanoparticulate delivery by laser produced a 6-fold enhancement in permeation. Fractional laser produced less enhancement of imiquimod delivery than conventional laser. Laser exposure increased follicular imiquimod accumulation from 0.80 to 5.81 μg/cm. ALA permeation from aqueous buffer, PEG 400, and PG with conventional laser treatment was 641-, 445-, and 104-fold superior to passive control. In vivo skin deposition of topically applied ALA examined by confocal microscopy indicated the same trend as the in vitro experiment, with aqueous buffer showing the greatest proporphyllin IX signaling. Diffusion of cosolvent molecules into ablated skin and drug partitioning from vehicle to skin are two predominant factors controlling laser-assisted delivery. In contrast to conventional laser, lateral drug diffusion was anticipated for fractional laser. Conclusions: Our results suggest that different drug delivery vehicles substantially influence drug penetration enhanced by lasers. [ABSTRACT FROM AUTHOR]

Delivery of diphencyprone (DPCP) and minoxidil to hair follicles and related cells is important in the treatment of alopecia. Here we report the development of 'squarticles,' nanoparticles formed from sebum-derived lipids such as squalene and fatty esters, for use in achieving targeted drug delivery to the follicles. Two different nanosystems, nanostructured lipid carriers (NLC) and nanoemulsions (NE), were prepared. The physicochemical properties of squarticles, including size, zeta potential, drug encapsulation efficiency, and drug release, were examined. Squarticles were compared to a free control solution with respect to skin absorption, follicular accumulation, and dermal papilla cell targeting. The particle size of the NLC type was 177 nm; that of the NE type was 194 nm. Approximately 80% of DPCP and 60% of minoxidil were entrapped into squarticles. An improved drug deposition in the skin was observed in the in vitro absorption test. Compared to the free control, the squarticles reduced minoxidil penetration through the skin. This may indicate a minimized absorption into systemic circulation. Follicular uptake by squarticles was 2- and 7-fold higher for DPCP and minoxidil respectively compared to the free control. Fluorescence and confocal images of the skin confirmed a great accumulation of squarticles in the follicles and the deeper skin strata. Vascular endothelial growth factor expression in dermal papilla cells was significantly upregulated after the loading of minoxidil into the squarticles. In vitro papilla cell viability and in vivo skin irritancy tests in nude mice suggested a good tolerability of squarticles to skin. Squarticles provide a promising nanocarrier for topical delivery of DPCP and minoxidil. [ABSTRACT FROM AUTHOR]

The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4-10 mJ with spot densities of 100-400 spots/cm(2). In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm(2)/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70-1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2-3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate skin permeation enhancement mediated by fractional laser for different permeants, including hydroquinone, imiquimod, fluorescein isothiocyanate-labeled dextran (FD), and quantum dots. Methods: Skin received a single irradiation of a fractional CO laser, using fluence of 2 or 4 mJ with densities of 100 ∼ 400 spots/cm. In vitro and in vivo skin penetration experiments were performed. Fluorescence and confocal microscopies for imaging delivery pathways were used. Results: The laser enhanced flux of small-molecule drugs 2 ∼ 5-fold compared to intact skin. A laser fluence of 4 mJ with a 400-spot/cm density promoted FD flux at 20 and 40 kDa from 0 (passive transport) to 0.72 and 0.43 nmol/cm/h, respectively. Microscopic images demonstrated a significant increase in fluorescence accumulation and penetration depth of macromolecules and nanoparticles after laser exposure. Predominant routes for laser-assisted delivery may be intercellular and follicular transport. CO laser irradiation produced 13-fold enhancement in follicular deposition of imiquimod. Laser-mediated follicular transport could deliver permeants to deeper strata. Skin barrier function as determined by transepidermal water loss completely recovered by 12 h after irradiation, much faster than conventional laser treatment (4 days). Conclusions: Fractional laser could selectively enhance permeant targeting to follicles such as imiquimod and FD but not hydroquinone, indicating the importance of selecting feasible drugs for laser-assisted follicle delivery. [ABSTRACT FROM AUTHOR]

Purpose: Diphencyprone (DPCP) is a therapeutic agent for treating alopecia areata. To improve skin absorption and follicular targeting nanostructured lipid carriers (NLCs) were developed. Methods: Nanoparticles were characterized by size, zeta potential, molecular environment, differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). In vitro and in vivo skin absorption experiments were performed. Fluorescence and confocal microscopes for imaging skin distribution were used. Results: NLCs with different designs were 208 ~ 265 nm with > 77% DPCP encapsulation. NLCs incorporating a cationic surfactant or more soybean phosphatidylcholine (SPC) showed higher lipophilicity compared to typical NLCs by Nile red emission. All NLCs tested revealed controlled DPCP release; burst release was observed for control. The formulation with more SPC provided 275 μg/g DPCP skin retention, which was greater than control and other NLCs. Intersubject deviation was reduced after DPCP loading into NLCs. Cyanoacrylate skin biopsy demonstrated greater follicular deposition for NLCs with more SPC compared to control. Cationic NLCs but not typical or SPC-containing carriers were largely internalized into keratinocytes. In vivo skin retention of NLCs with more SPC was higher than free control. Confocal imaging confirmed localization of NLCs in follicles and intercellular lipids of stratum corneum. Conclusions: This work encourages further investigation of DPCP absorption using NLCs with a specific formulation design. [ABSTRACT FROM AUTHOR]

We aimed to develop liposomes for loading both cisplatin and quantum dots (QDs) for both drug delivery and bioimaging. The resultant quantum-dot-liposomes (QDLs) with cisplatin were characterized using dynamic light scattering, transmission electron microscopy (TEM), encapsulation efficiencies, and fluorescence intensity. QDLs composed of CdSe or CdSe/ZnS QDs represented a size of about 100 nm. The QDLs were prepared at a high QD loading efficiency of nearly 100 %. Most QDs were located within the liposomal bilayers as evidenced by TEM. Slow and sustained cisplatin release from QDLs was achieved. The cellular uptake of QDLs demonstrated effective internalization and significant fluorescence in melanoma cells. The signal derived from QDLs could be observed by different wavelength settings. The cisplatin-containing QDLs revealed higher cytotoxic activity compared to an equal dose of free cisplatin. CdSe/ZnS QDLs were intravenously administered to mice, and the biodistribution was observed with an in vivo imaging system. Significant fluorescence signal and cisplatin accumulation were detected in the brain and skin, as verified by ex vivo imaging and drug distribution. Liposomal inclusion could reduce the reticuloendothelial system uptake of QDs and cisplatin. QDLs evaluated in this study represent a new potential method for theranostic purposes. [ABSTRACT FROM AUTHOR]

Aim:To investigate the in vitro and in vivo percutaneous absorption of seleno-L-methionine (Se-L-M), an ultraviolet (UV)-protecting agent, from aqueous solutions.Methods:Aqueous solutions of Se-L-M were prepared in pH 4, 8, and 10.8 buffers. The pH 8 buffer contained 30% glycerol, propylene glycol (PG) and polyethylene glycol (PEG) 400. The in vitro skin permeation of Se-L-M via porcine skin and nude mouse skin was measured and compared using Franz diffusion cells. The in vivo skin tolerance study was performed, which examined transepidermal water loss (TEWL), skin pH and erythema.Results:In the excised porcine skin, the flux was 0.1, 11.4 and 8.2 μg·cm−2·h−1 for the pH 4, 8, and 10.8 buffers, respectively. A linear correlation between the flux and skin deposition was determined. According to permeation across skin with different treatments (stripping, delipidation, and ethanol treatments), it was determined that the intracellular route comprised the predominant pathway for Se-L-M permeation from pH 8 buffer. Aqueous solutions of seleno-DL-methionine (Se-DL-M), selenium sulfide and selenium-containing quantum dot nanoparticles were also used as donor systems. The DL form showed a lower flux (7.0 vs 11.4 μg·cm−2·h−1) and skin uptake (23.4 vs 47.3 μg/g) as compared to the L form, indicating stereoselective permeation of this compound. There was no or only negligible permeation of selenium sulfide and quantum dots into and across the skin. With in vivo topical application for 4 and 8 h, the skin deposition of Se-L-M was about 7 μg/g, and values were comparable to each other. The topical application of Se-L-M for up to 5 d did not caused apparent skin irritation. However, slight inflammation of the dermis was noted according to the histopathological examination.Conclusion:Se-L-M was readily absorbed by the skin in both the in vitro and in vivo experiments. The established profiles of Se-L-M skin absorption will be helpful in developing topical products of this compound. [ABSTRACT FROM AUTHOR]

Purpose: Most of the investigations into laser-assisted skin permeation have used the intact skin as the permeation barrier. Whether the laser is effective in improving cutaneous delivery via barrier-defective skin is still unclear.Methods: In this study, ablative (Er:YAG) and non-ablative (Er:glass) lasers were examined for the penetration of peptide and siRNA upon topical application on in vitro skin with a healthy or disrupted barrier.Results: An enhanced peptide flux (6.9 fold) was detected after tape stripping of the pig stratum corneum (SC). A further increase of flux to 11.7 fold was obtained after Er:YAG laser irradiation of the SC-stripped skin. However, the application of Er:glass modality did not further raise the flux via the SC-stripped skin. A similar trend was observed in the case of psoriasiform skin. Conversely, the flux was enhanced 3.7 and 2.6 fold after treatment with the Er:YAG and the Er:glass laser on the atopic dermatitis (AD)-like skin. The 3-D skin structure captured by confocal microscopy proved the distribution of peptide and siRNA through the microchannels and into the surrounding tissue.Conclusions: The fractional laser was valid for ameliorating macromolecule permeation into barrier-disrupted skin although the enhancement level was lower than that of normal skin. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a multifaceted inflammatory skin condition characterized by the involvement of various cell types, such as keratinocytes, macrophages, neutrophils, and mast cells. Research indicates that flavonoids possess anti-inflammatory properties that may be beneficial in the management of AD. However, the investigation of the glycoside forms for anti-AD therapy is limited. We aimed to assess the ability of quercetin-3-O-glycosides in treating AD-like lesions through in silico-, cell-, and animal-based platforms. The glycosylated flavonols of quercitrin, isoquercitrin, and rutin were used in this study. We also tried to understand the influence of glycone type on the bioactivity and skin delivery of glycosides. The glycosides effectively reduced the overexpression of proinflammatory effectors such as interleukin (IL)-6, chemokine (C-X-C motif) ligand (CXCL)1, CXCL8, regulated upon activation normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC) in the activated keratinocytes. This reduction could be due to the inhibition of extracellular signal-regulated kinase (ERK) and p38 phosphorylation. Isoquercitrin (but not quercitrin and rutin) could arrest the upregulated IL-6 and CCL5 in the macrophage model. The glycosides significantly prevented histamine release from RBL-2H3 cells. The skin absorption examination showed a greater permeation of quercitrin and isoquercitrin than rutin with dual sugar moieties due to the smaller molecular volume and higher lipophilicity. The skin deposition of quercitrin and isoquercitrin was enhanced by about 11-fold in the stripped and delipidized skins, which mimicked AD lesions. The in vivo dinitrochlorobenzene (DNCB)-induced AD mouse model demonstrated less erosion, scaling, and epidermal hyperplasia after topical isoquercitrin treatment. The concentration of cytokines/chemokines in the lesion was decreased by isoquercitrin. These effects were similar to those of tacrolimus ointment. The immunohistochemistry (IHC) displayed the reduction of epidermal hyperproliferation and immune cell infiltration by topical isoquercitrin. The results indicated that the delivery of quercetin glycosides could provide an efficient and safe way to treat AD inflammation. [ABSTRACT FROM AUTHOR]