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Niacinamide (NIA) is a water-soluble vitamin that is widely used in the treatment of skin diseases. Moreover, NIA displays antioxidant effects and helps repair damaged DNA. Recent studies showed that particulate matter 2.5 (PM2.5) induced reactive oxygen species (ROS), causing disruption of DNA, lipids, and proteins; mitochondrial depolarization, and apoptosis of skin keratinocytes. Here, we investigated the protective effects of NIA on PM2.5-induced oxidative stress in human HaCaT keratinocytes. We found that NIA could inhibit the ROS generation induced by PM2.5, as well blocked the PM2.5-induced oxidation of molecules, such as lipids, proteins, and DNA. Furthermore, NIA alleviated PM2.5-induced accumulation of cellular Ca2+, which caused cell membrane depolarization and apoptosis, and reduced the number of apoptotic cells. Collectively, the findings show that NIA can protect keratinocytes from PM2.5-induced oxidative stress and cell damage.
The stratum corneum is the outermost skin layer that obstructs the delivery of active ingredients found in cosmeceutical products. Chemical peels and microbeads have been used to overcome this layer, but these methods can cause side effects and are not environmentally friendly. While microneedles do not share the dangers mentioned above, they are currently only available as patches, which makes them unsuitable to be used with products that are usually applied onto a large area of the skin surface. Therefore, the aim of this study was to develop microneedle-like particles (MLP) whose needles would disrupt the skin during the rubbing process. A modified approach taken from conventional micromolding techniques was used to make the MLPs. The experimental results show that the fabricated structures had the required mechanical strength. Furthermore, after the application of the MLPs, the permeability of two fluorescent dyes, fluorescein sodium salt and sulforhodamine B increased to 217.6% ± 25.6% and 251.7% ± 12.8% respectively. Additionally, the permeability of a model drug, niacinamide, was shown to have increased to 193.8% ± 29.9%. Cryosectioned porcine slices also confirmed the ability of MLPs to enhance skin permeability by revealing a deeper penetration of the applied fluorescent dye. Altogether, the results demonstrate the potential of MLPs to be used as safe skin permeability enhancers that can be applied all over the skin.
Niacinamide (NIA) has been widely used in halting the features of ageing by acting as an antioxidant and preventing dehydration. NIA's physicochemical properties suggest difficulties in surpassing the barrier imposed by the stratum corneum layer to reach the target in the skin. To improve cutaneous delivery of NIA, a hybrid nanogel was designed using carrageenan and polyvinylpyrrolidone polymers combined with jojoba oil as a permeation enhancer. Three different types of transethosomes were prepared by the thin-film hydration method, made distinct by the presence of either an edge activator or a permeation enhancer, to allow for a controlled delivery of NIA. Formulations were characterized by measurements of size, polydispersity index, zeta potential, encapsulation efficiency, and loading capacity, and by evaluating their chemical interactions and morphology. Skin permeation assays were performed using Franz diffusion cells. The hybrid hydrogels exhibited robust, porous, and highly aligned macrostructures, and when present, jojoba oil changed their morphology. Skin permeation studies with transethosomes-loaded hydrogels showed that nanogels per se exhibit a more controlled and enhanced permeation, in particular when jojoba oil was present in the transethosomes. These promising nanogels protected the human keratinocytes from UV radiation, and thus can be added to sunscreens or after-sun lotions to improve skin protection.
Xenon is confirmed to diffuse readily through membranes and has properties of transdermal enhancer. In this study, the ability of xenon to regulate the transdermal diffusion of niacinamide was investigated using a model of an artificial skin analogue of Strat-M™ membranes in Franz cells. Based on the data obtained, we found that in the simplified biophysical model of Strat-M™ membranes xenon exerts its enhancer effect based on the heterogeneous nucleation of xenon at the interfaces in the microporous structures of Strat-M™ membranes.
Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart containing two additional excipients: niacinamide, to increase early absorption, and L-arginine, to optimize stability. The aim of this study was to evaluate the impact of niacinamide on insulin aspart absorption and to investigate the mechanism of action underlying the accelerated absorption.
Niacinamide-containing moisturisers are known be efficacious in alleviating dry skin conditions and improving stratum corneum (SC) barrier function. However, the mechanisms of action of niacinamide at the molecular level in the SC are still not well understood. Previously, we have reported the development of novel methods to probe SC barrier properties in vivo. The aim of the present study was to characterise changes in Trans Epidermal Water Loss (TEWL), corneocyte surface area and maturity, selected protease activities and SC thickness after repeated application of a simple vehicle containing niacinamide. A commercial formulation was also included as a reference. The left and right mid-volar forearms of 20 healthy volunteers were used as study sites, to which topical formulations were applied twice daily for 28 days. After successive tape-stripping, corneocyte maturity and surface area were assessed. In addition, activity of the desquamatory kallikrein (KLK) protease enzymes KLK5 and KLK7, and tryptase and plasmin (implicated in inflammatory process) were measured using a fluorogenic probe assay. The amount of protein removed and TEWL were also recorded. SC thickness before and after treatment was determined using Confocal Raman Spectroscopy (CRS). Overall (i) corneocyte maturity and surface area decreased with increasing number of tape strips, (ii) activity of both the desquamatory and inflammatory enzymes was highest in the outer layers of the SC and decreased with depth (iii) TEWL increased as more SC layers were removed. Furthermore, areas treated with formulations containing niacinamide were significantly different to pre-treatment baseline and untreated/vehicle-control treated sites, with larger and more mature corneocytes, decreased inflammatory activity, decreased TEWL and increased SC thickness. These data (a) confirm the utility of measures and metrics developed previously for the non-invasive assay of SC barrier function, (b) present an holistic picture of a SC compartment managing barrier function through dynamic optimisation of pathlength and quality of building materials used, and (c) shed new light on niacinamide as a topical formulation adjunct with unique SC barrier-augmentation properties.
The current work aimed to examine the properties of oral supplementation of niacinamide and undenatured type II collagen (UCII) on the inflammation and joint pain behavior of rats with osteoarthritis (OA). Forty-nine Wistar rats were allocated into seven groups; control (no MIA), MIA as a non-supplemental group with monosodium iodoacetate (MIA)-induced knee osteoarthritis, MIA + undenatured type II collagen (UCII) at 4 mg/kg BW, MIA + Niacinamide at 40 mg/kg BW (NA40), MIA + Niacinamide at 200 mg/kg BW (NA200), MIA + UCII + NA40 and MIA + UCII + NA200. Serum IL-1β, IL-6, TNF-α, COMP, and CRP increased in rats with OA and decreased in UCII and NA groups (p < 0.05). Rats with osteoarthritis had greater serum MDA and knee joint MMP-3, NF-κB, and TGβ protein levels and decreased in treated groups with UCII and NA (p < 0.05). The rats with OA also bore elevated joint diameters with joint pain behavior measured as decreased the stride lengths, the paw areas, and the paw widths, and increased the Kellgren-Lawrence and the Mankin scores (p < 0.05) and decreased in UCII treated groups. These results suggest the combinations with the UCII + NA supplementation as being most effective and reduce the inflammation responses for most OA symptoms in rats.
Background. Multiple modalities have been used in the treatment of melasma with variable success. Niacinamide has anti-inflammatory properties and is able to decrease the transfer of melanosomes. Objective. To evaluate the therapeutic effect of topical niacinamide versus hydroquinone (HQ) in melasma patients. Patients and Methods. Twenty-seven melasma patients were randomized to receive for eight weeks 4% niacinamide cream on one side of the face, and 4% HQ cream on the other. Sunscreen was applied along the observation period. They were assessed by noninvasive techniques for the evaluation of skin color, as well as subjective scales and histological sections initially and after the treatment with niacinamide. Results. All patients showed pigment improvement with both treatments. Colorimetric measures did not show statistical differences between both sides. However, good to excellent improvement was observed with niacinamide in 44% of patients, compared to 55% with HQ. Niacinamide reduced importantly the mast cell infiltrate and showed improvement of solar elastosis in melasma skin. Side effects were present in 18% with niacinamide versus 29% with HQ. Conclusion. Niacinamide induces a decrease in pigmentation, inflammatory infiltrate, and solar elastosis. Niacinamide is a safe and effective therapeutic agent for this condition.
An increasing number of people are suffering from hair loss disorders. Niacinamide has long been used as an active ingredient for anti-hair loss preparations but the exact mechanism has not been clearly elucidated yet. The effects of niacinamide were investigated in cultured human dermal papilla cells (hDPCs).
Polyethylene glycols (PEGs) and PEG derivatives are used in a range of cosmetic and pharmaceutical products. However, few studies have investigated the influence of PEGs and their related derivatives on skin permeation, especially when combined with other solvents. Previously, we reported niacinamide (NIA) skin permeation from a range of neat solvents including propylene glycol (PG), Transcutol® P (TC), dimethyl isosorbide (DMI), PEG 400 and PEG 600. In the present work, binary and ternary systems composed of PEGs or PEG derivatives combined with other solvents were investigated for skin delivery of NIA. In vitro finite dose studies were conducted (5 μL/cm2) in porcine skin over 24 h. Higher skin permeation of NIA was observed for all vehicles compared to PEG 400. However, overall permeation for the binary and ternary systems was comparatively low compared with results for PG, TC and DMI. Interestingly, values for percentage skin retention of NIA for PEG 400:DMI and PEG 400:TC were significantly higher than values for DMI, TC and PG (p < 0.05). The findings suggest that PEG 400 may be a useful component of formulations for the delivery of actives to the skin rather than through the skin. Future studies will expand the range of vehicles investigated and also look at skin absorption and residence time of PEG 400 compared to other solvents.
The in vitro skin penetration of pharmaceutical or cosmetic ingredients is usually assessed in human or animal tissue. However, there are ethical and practical difficulties associated with sourcing these materials; variability between donors may also be problematic when interpreting experimental data. Hence, there has been much interest in identifying a robust and high throughput model to study skin permeation that would generate more reproducible results. Here we investigate the permeability of a model active, niacinamide (NIA), in (i) conventional vertical Franz diffusion cells with excised human skin or porcine skin and (ii) a recently developed Parallel Artificial Membrane Permeation Assay (PAMPA) model. Both finite and infinite dose conditions were evaluated in both models using a series of simple NIA solutions and one commercial preparation. The Franz diffusion cell studies were run over 24 h while PAMPA experiments were conducted for 2.5 h. A linear correlation between both models was observed for the cumulative amount of NIA permeated in tested models under finite dose conditions. The corresponding correlation coefficients (r2) were 0.88 for porcine skin and 0.71 for human skin. These results confirm the potential of the PAMPA model as a useful screening tool for topical formulations. Future studies will build on these findings and expand further the range of actives investigated.
Alterations in metabolism in skin are accelerated by environmental stressors such as solar radiation, leading to premature aging. The impact of aging on mitochondria is of interest given their critical role for metabolic output and the finding that environmental stressors cause lowered energy output, particularly in fibroblasts where damage accumulates. To better understand these metabolic changes with aging, we performed an in-depth profiling of the expression patterns of dermal genes in face, forearm, and buttock biopsies from females of 20-70 years of age that encode for all subunits comprising complexes I-V of the mitochondrial electron transport chain. This complements previous preliminary analyses of these changes. "Oxidative phosphorylation" was the top canonical pathway associated with aging in the face, and genes encoding for numerous subunits had decreased expression patterns with age. Investigations on fibroblasts from older aged donors also showed decreased gene expression of numerous subunits from complexes I-V, oxidative phosphorylation rates, spare respiratory capacity, and mitochondrial number and membrane potential compared to younger cells. Treatment of older fibroblasts with nicotinamide (Nam) restored these measures to younger cell levels. Nam increased complexes I, IV, and V activity and gene expression of representative subunits. Elevated mt-Keima staining suggests a possible mechanism of action for these restorative effects via mitophagy. Nam also improved mitochondrial number and membrane potential in younger fibroblasts. These findings show there are significant changes in mitochondrial functionality with aging and that Nam treatment can restore bioenergetic efficiency and capacity in older fibroblasts with an amplifying effect in younger cells.
Glioblastoma multiforme (GBM) is a CNS (central nervous system) malignancy with a low cure rate. Median time to progression after standard treatment is 7 months and median overall survival is 15 months [1]. Post-treatment vasculogenesis promoted by recruitment of bone marrow derived cells (BMDCs, CD11b+ myelomonocytes) is one of main mechanisms of GBM resistance to initial chemoradiotherapy treatment [2]. Local secretion of SDF-1, cognate ligand of BMDCs CXCR4 receptors attracts BMDCs to the post-radiation tumor site.[3]. This SDF-1 hypoxia-dependent effect can be blocked by AMD3100 (plerixafor) [4]. We report a GBM case treated after chemo- radiotherapy with plerixafor and a combination of an mTOR, a Sirt1 and an EGFRvIII inhibitor. After one year temozolomide and the EGFRvIII inhibitor were stopped. Plerixafor, and the MTOR and Sirt-1 inhibitors were continued. He is in clinical and radiologic remission 30 months from the initiation of his adjuvant treatment. To our knowledge, this is the first report of a patient treated for over two years with a CXCR4 inhibitor (plerixafor), as part of his adjuvant treatment. We believe there is sufficient experimental evidence to consider AMD3100 (plerixafor) part of the adjuvant treatment of GBM.
A novel technology for the delivery of active substances to the skin based on microfibers loaded with dried active substances was developed. The objective of this work was to demonstrate deposition of the active substances on the skin including concurrent cleansing properties of the wipe. As model active substance to measure deposition capacity Niacinamide was used and as parameter to measure cleansing capacities of the wipe squalene uptake was measured. Wipes loaded with niacinamide were used in the face and the forearm of 25 subjects. By means of Raman spectrometry the deposited niacinamide was analyzed before and after application. Wipes used on the face were analyzed for squalene to assess skin cleansing properties and for residual niacinamide. Forearm analysis including placebo and verum on left and right arm respectively was performed to rule out changes of the skin through application of the tissue. Measured amounts of niacinamide from face application demonstrate statistically significant results in the study population. Analysis of the wipes used show a liberation of 28.3% of niacinamide from the wipes and an uptake of 1.7 mg squalene per wipe. Results from forearm application show statistically significant differences (p < 0.05) between placebo and active for the complete study population. Sub group analyses are significant for both gender and ethnicity for face and forearm analysis respectively. Results clearly demonstrate deposition of niacinamide on the skin and the cleansing properties of the wipe. The institutional review board approved this prospective study.
The main challenges in developing zeolites as cosmetic drug delivery systems are their cytotoxicities and the formation of drug-loading pore structures. In this study, Au-decorated zeolite nanocomposites were synthesized as an epidermal delivery system. Thus, 50 nm-sized Au nanoparticles were successfully deposited on zeolite 13X (super cage (α) and sodalite (β) cage structures) using the Turkevich method. Various cosmetic drugs, such as niacinamide, sulforaphane, and adenosine, were loaded under in vitro and in vivo observations. The Au-decorated zeolite nanocomposites exhibited effective cosmetic drug-loading efficiencies of 3.5 to 22.5 wt% under various conditions. For in vitro cytotoxic observations, B16F10 cells were treated with various cosmetic drugs. Niacinamide, sulforaphane, and adenosine-loaded Au-decorated zeolite nanocomposites exhibited clear cell viability of over 80%. Wrinkle improvement and a reduction in melanin content on the skin surface were observed in vivo. The adenosine delivery system exhibited an enhanced wrinkle improvement of 203% compared to 0.04 wt% of the pure adenosine system. The niacinamide- and sulforaphane-loaded Au-decorated zeolite nanocomposites decreased the skin surface melanin content by 123% and 222%, respectively, compared to 2 and 0.01 wt% of pure niacinamide and sulforaphane systems, respectively. As a result, Au-decorated zeolite nanocomposites show great potential as cosmetic drug epidermal delivery systems for both anti-aging and lightening effects.
The skin-associated microbiome plays an important role in general well-being and in a variety of treatable skin conditions. In this regard, endogenous antimicrobial peptides have both a direct and indirect role in determining the composition of the microbiota. We demonstrate here that certain small molecular species can amplify the antimicrobial potency of naturally occurring antimicrobial peptides. In this study, we have used niacinamide, a form of vitamin B3 naturally found in foods and widely used in cosmetic skincare products, and two of its structural analogs, to investigate their cooperativity with the human antimicrobial peptide LL37 on the bacterium Staphylococcus aureus. We observed a clear synergistic effect of niacinamide and, to some extent, N-methylnicotinamide, whereas isonicotinamide showed no significant cooperativity with LL37. Adaptively biased molecular dynamics simulations using simplified model membrane substrates and single peptides revealed that these molecules partition into the headgroup region of an anionic bilayer used to mimic the bacterial membrane. The simulated effects on the physical properties of the simulated model membrane are well correlated with experimental activity observed in real biological assays despite the simplicity of the model. In contrast, these molecules have little effect on zwitterionic bilayers that mimic a mammalian membrane. We conclude that niacinamide and N-methylnicotinamide can therefore potentiate the activity of host peptides by modulating the physical properties of the bacterial membrane, and to a lesser extent through direct interactions with the peptide. The level of cooperativity is strongly dependent on the detailed chemistry of the additive, suggesting an opportunity to fine-tune the behavior of host peptides.
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