Layers Of Stratum Corneum Research Articles

Skin Improvement of the Composition Containing Nano-exosome Derived from Aloe vera Bark Callus as New Type of Transdermal Delivery System

Purpose: The purpose of this study was to extract nano-exosomes from Aloe vera bark callus and validate their effects on collagen synthesis and skin corneous improvement.Methods: Human dermal fibroblast (HDF) was used to validate collagen synthesis, while HaCaT cells, a human keratin cell line, were used to verify absorption capability. The Folin–Denis technique was used to determine the polyphenol content. In addition, lotion formulations and skin application experiments were also carried out.Results: Nano-exosomes with size ranging 50–150 nm were successfully isolated from Aloe vera bark callus (alosomes). Alosomes produced 22.11% more collagen in HDF than Aloe vera bark extract at 1.0% concentration. In the cytotoxicity test, 80% of cells were survived at concentrations of 1% or less. After one hour, a considerable quantity was transported into the cytoplasm of HaCaT cells. The polyphenol concentration was four times that of Aloe vera bark extract. Skin tests using alosome-containing lotion demonstrated that skin surface, hydration, and elasticity were improved after 4 weeks. Moisture contents of the stratum corneum and dermis layer were improved, whereas moisture content of corneous was reduced after 4 weeks.Conclusion: The skin-improving effect of nano-exosomes derived from Aloe vera bark callus is shown in this study, indicating its potential as a functional cosmetic raw material.

Moisturizing at a molecular level - The basis of Corneocare.

This review covers the last 20 years of research we and our collaborators have conducted on ethnic differences in facial skin moisturization placed in historical context with previous research. We have focussed particularly on the biochemical and cellular gradients of the stratum corneum (SC) with the aim of discovering new skin moisturization and SC maturation mechanisms, identifying new technologies and/or providing conceptual innovations for ingredients that will improve our understanding and treatment of dry skin. Specifically, we discuss gradients for corneodesmosomes and proteases, corneocyte phenotype-inducing enzymes, filaggrin and natural moisturizing factor (NMF), and barrier lipids. These gradients are interdependent and influence greatly corneocyte maturation. The interrelationship between corneodesmolysis and the covalent attachment of ω-hydroxy ceramides and ω-hydroxy fatty acids to the corneocyte protein envelope forming the corneocyte lipid envelope is especially relevant in our new understanding of mechanisms leading to dry skin. This process is initiated by a linoleoyl-ω-acyl ceramide transforming enzyme cascade including 12R lipoxygenase (12R-LOX), epidermal lipoxygenase-3 (eLOX3), epoxide hydrolase 3 (EPHX3), short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7), ceramidase and transglutaminase 1. Our research has opened the opportunity of using novel treatment systems for dry skin based on lipids, humectants, niacinamide and inhibitors of the plasminogen system. It is clear that skin moisturization is a more complex mechanism than simple skin hydration.

Microneedles: Recent advances and development in the field of transdermal drug delivery technology

Microneedles have emerged as a novel therapeutic modality in transdermal drug delivery system. The concept of microneedle has caught attention of the investigators owing to its immense utilities and unique promising features of painless drug delivery by crossing the impervious barrier layer of stratum corneum of skin efficiently in a non-invasive manner. It provides excellent therapeutic potency and bioavailability of drugs compared to most other conventional drug delivery routes. Microneedles have supremacy on avoidance of pre-systemic first pass metabolism of administered drugs, better patient compliance and avoidance of gastric irritation which outweighs the adherence of other conventional drug delivery system. As a trendy approach in the pharmaceutical and biomedical field, its applications are constantly evolving due to its ability to deliver large molecules with ionic and hydrophilic nature along with delivery of other products like insulin, vaccine, vitamins, peptides, oligonucleotides etc. The review provides an insight on recent advances of microneedles by emphasizing on various types, fabrication techniques, fabrication materials and various pharmaceutical and biomedical applications of microneedles along with some approved marketed microneedle products.
 Keywords: Microneedles, types, fabrication techniques, commercial products

A Dual-Modality Imaging Method Based on Polarimetry and Second Harmonic Generation for Characterization and Evaluation of Skin Tissue Structures

The characterization and evaluation of skin tissue structures are crucial for dermatological applications. Recently, Mueller matrix polarimetry and second harmonic generation microscopy have been widely used in skin tissue imaging due to their unique advantages. However, the features of layered skin tissue structures are too complicated to use a single imaging modality for achieving a comprehensive evaluation. In this study, we propose a dual-modality imaging method combining Mueller matrix polarimetry and second harmonic generation microscopy for quantitative characterization of skin tissue structures. It is demonstrated that the dual-modality method can well divide the mouse tail skin tissue specimens' images into three layers of stratum corneum, epidermis, and dermis. Then, to quantitatively analyze the structural features of different skin layers, the gray level co-occurrence matrix is adopted to provide various evaluating parameters after the image segmentations. Finally, to quantitatively measure the structural differences between damaged and normal skin areas, an index named Q-Health is defined based on cosine similarity and the gray-level co-occurrence matrix parameters of imaging results. The experiments confirm the effectiveness of the dual-modality imaging parameters for skin tissue structure discrimination and assessment. It shows the potential of the proposed method for dermatological practices and lays the foundation for further, in-depth evaluation of the health status of human skin.

Evaluation of a Novel Skin Emollient Cream on Skin Lipidome and Lipid Organization

Introduction: The stratum corneum (SC) matrix is composed of free fatty acids, cholesterol, and ceramides (CERs), which play a key role in the skin barrier function. Changes in the composition and content of skin lipids will affect the function of the skin barrier. The effect of a glycerol/petrolatum-based emollient (G/P-emollient) cream on the lipid profiles of isolated ex vivo human SC and the SC of a reconstructed human epidermis (RHE) model was measured. Methods: The spatial organization of the cream and the isolated SC intercellular matrix were studied using X-ray diffraction. The inter-bilayer distances in the multi-lamellar lipid structures and lattice type were analyzed using small-angle X-ray scattering and wide-angle X-ray scattering (WAXS), respectively. Lipidomic analysis using shotgun lipidomics was performed on RHE models to quantify CER classes and chain lengths. This technology enables the analysis of thousands of lipids in a single biological sample. Results: The crystallized components of the cream are lipids, which were mainly packed in orthorhombic lattices, as well as hexagonal lattices and were similar to the SC structure. The cream penetrated the SC but did not alter the WAXS profile. It increased the amount of higher carbon number CERs (>42 carbons) and decreased lower carbon number CERs (<42 carbons). All chain length of CERs and acyl-CER classes (CER EOS, EOH, EOP, EOdS) were increased as the total CER classes. A decrease of the CER C34 for hydroxylated and non-hydroxylated CERs was also observed. The cream altered the S and P CER forms (increased the NP/NS and AP/AS ratios), indicating it could reduce the relative feedback mechanism observed in inflammatory pathologies, for example, atopic dermatitis. The cream increased CER NP, which is decreased in dry skin. Conclusion: G/P-emollient cream may be beneficial for skin pathologies by modifying SC lipids, balancing CER levels and ratios, and improving the barrier function. Importantly, the cream structure mimics that of the SC and penetrated the lower SC layers without compromising its lamellar structure.

Biomimetic Stratum Corneum Liposome Models: Lamellar Organization and Permeability Studies

The stratum corneum (SC), the outer layer of the skin, plays a crucial role as a barrier protecting the underlying cells from external stress. The SC comprises three key components: ceramide (CER), free fatty acid (FFA), and cholesterol, along with small fractions of cholesterol sulfate and cholesterol ester. In order to gain a deeper understanding about the interdependence of the two major components, CER and FFA, on the organizational, structural, and functional properties of the SC layer, a library of SC lipid liposome (SCLL) models was developed by mixing CER (phytosphingosine or sphingosine), FFA (oleic acid, palmitic acid, or stearic acid), cholesterol, and cholesterol sulfate. Self-assembly of the SC lipids into lamellar phases was first confirmed by small-angle X-ray scattering. Short periodicity and long periodicity phases were identified for SCLLs containing phytosphingosines and sphingosine CERs, respectively. Furthermore, unsaturation in the CER acyl and FFA chains reduced the lipid conformational ordering and packing density of the liposomal bilayer, which were measured by differential scanning calorimetry and Fourier transform infrared spectroscopy. The introduction of unsaturation in the CER and/or FFA chains also impacted the lamellar integrity and permeability. This extensive library of SCLL models exhibiting physiologically relevant lamellar phases with defined structural and functional properties may potentially be used as a model system for screening pharmaceuticals or cosmetic agents.

Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals.

Transdermal delivery provides numerous benefits over conventional routes of administration. However, this strategy is generally limited to a few molecules with specific physicochemical properties (low molecular weight, high potency, and moderate lipophilicity) due to the barrier function of the stratum corneum layer. Researchers have developed several physical enhancement techniques to expand the applications of the transdermal field; among these, microneedle technology has recently emerged as a promising platform to deliver therapeutic agents of any size into and across the skin. Typically, hydrophilic biomolecules cannot penetrate the skin by passive diffusion. Microneedle insertion disrupts skin integrity and compromises its protective function, thus creating pathways (microchannels) for enhanced permeation of macromolecules. Microneedles not only improve stability but also enhance skin delivery of various biomolecules. Academic institutions and industrial companies have invested substantial resources in the development of microneedle systems for biopharmaceutical delivery. This review article summarizes the most recent research to provide a comprehensive discussion about microneedle-mediated delivery of macromolecules, covering various topics from the introduction of the skin, transdermal delivery, microneedles, and biopharmaceuticals (current status, conventional administration, and stability issues), to different microneedle types, clinical trials, safety and acceptability of microneedles, manufacturing and regulatory issues, and the future of microneedle technology.

In Vitro-In Vivo Correlations (IVIVC) for Predicting the Clinical Performance of Metronidazole Topical Creams Intended for Local Action.

The safety and efficacy of a generic medicine can be confirmed by demonstrating bioequivalence (BE) between the generic product and its reference listed drug (RLD) by measuring drug concentrations in the blood following administration. However, for topical dermatological products that are not absorbed into the systemic circulation, clinical trials in patients are required. The objective of this investigation was to use an in vitro method to predict in vivo performance by correlating in vitro release testing (IVRT) data with tape stripping (TS) data following the application of metronidazole (MTZ) creams to the skin of healthy human participants. Whereas IVRT is generally used to characterize the release of a drug from topical products across a synthetic membrane into a suitable receptor medium, TS involves the sequential removal of layers of stratum corneum (SC) with an adhesive tape to determine the amount of the drug in the skin. The resulting IVRT and TS data were correlated using the IVRT parameter of the apparent release constant (ARC), which is the slope obtained from the release rate profile, with the TS parameter of the area under the curve (AUC) obtained from a plot of the amount of drug per tape strip vs. the relative SC depth. A rank order relationship for these parameters was established for the reference and test products. A graph of AUC vs. ARC was plotted to establish a Level C in vitro-in vivo correlation (IVIVC). Although the ARC for T1 was slightly lower than that for the reference, the rank order was essentially consistent. A linear relationship was observed between the AUCs and ARCs. The equation derived was used to predict the AUCs for all the tested products based on their respective ARCs. The predicted AUC values based on the observed ARCs were similar to the observed AUCs. The lower and upper limits for the in vitro and in vivo parameters for BE were computed based on regulatory acceptance criteria. In order to predict BE from the IVRT studies, the values of the ARC should be between 30.50 and 47.67 when comparing test and reference cream products containing MTZ.

Anatomical and functional differences of the skin in various ethnic groups

Besides the differences in skin and hair color among different ethnic groups, morphological and functional differences in skin and hair have also been demonstrated. The color of skin and hair is determined by two types of melanin, eumelanin (brown to black pigment) and phaeomelanin (red to yellow pigment). In addition to the individual mixture of these pigment types, there are also differences in the melanosome arrangement of Caucasian, Asian, and African skin. Although the epidermis thickness is the same in all people, darker skin has ahigher number of stratum corneum layers and athicker dermis with ahigher number of fibroblasts. The hairs of different ethnic groups also vary regarding shape and thickness: they are round in Asians, elliptical in Blacks and intermediate in Whites. Hair diameter is the greatest in Asians, followed by Blacks and is the smallest in Whites, whereas the number of hairs is highest in Whites, followed by that in Asians and Blacks.

Potential of electro-sprayed purified mangiferin nanoparticles for anti-aging cosmetic applications.

The fabrication of mangiferin nanoparticles using an electrospraying technique is a new and promising method for developing nanoparticles with higher efficiency and safety. This study aimed to fabricate mangiferin nanoparticles (MNPs) using cellulose acetate (CA) as a polymer at various parameters using electrospraying. Commercial mangiferin (CM) was purified from 88.46 to 95.71% by a recrystallization method to improve its purity and biological activities and remove any residue. The properties of recrystallized mangiferin (RM) were characterized using DSC, FTIR, X-ray diffraction (XRD) and HPLC. Then its biological activity and proteomics were determined. Proteomics analysis of RM showed that up-regulated proteins were involved in more biological processes than CM. MNPs were fabricated by varying the electrospraying parameters including voltage, the distance between the needle-tip-collector and flow rate. Skin permeation, release and irritation were also evaluated. The results revealed that the average particle size of the MNPs ranged between 295.47 ± 5.58 and 448.87 ± 3.00 nm, and had a smooth spherical morphology in SEM images. The MNPs also showed good potential in antioxidant and anti-aging properties. The encapsulation efficiency of MNPs was determined to be 85.31%. From skin permeation studies of CM, RM, and MNPs, the mangiferin content was found in the stratum corneum and dermis skin layers. Moreover, the MNPs solution had 23.68 ± 0.27% and 11.98 ± 0.13% of mangiferin in the stratum corneum and viable epidermis and dermis, respectively. Additionally, the irritation test by HET-CAM was mild and safe. Therefore, MNPs produced by electrospraying are a promising delivery system for cosmetic/cosmeceutical applications.

Review Artikel: Metode Teknologi Dalam Sistem Penghantaran Obat Transdermal Sediaan Patch

&#x0D; &#x0D; &#x0D; &#x0D; Transdermal is a route of drug administration through the skin, where many lipid layers are difficult to penetrate so that transdermal preparations are needed as a place for drug entry, for example creams and gels. The mechanism of drug delivery is through diffusion of the stratum corneum layer through lipid molecules, before releasing the drug in a controlled and constant manner followed by various other benefits and aims to increase the pharmacological effect in order to reach the maximum level. However, the permeability of the drug is not strong enough to pass through the stratum corneum. So we need a transdermal preparation that can work optimally and overcome the obstacles. This study aims to demonstrate the form, evaluation, formulation, and application of transdermal preparations in new drug delivery systems. Method used literature review of the 10 most journal articles and contains related information. Based on the research results, transdermal dosage forms differ depending on the level of concentration and each technological method needs adapted to the characteristics drug and the route of drug delivery given.&#x0D; &#x0D; &#x0D; &#x0D;

Hyaluronic acid skin penetration evaluated by tape stripping using ELISA kit assay

Hyaluronic Acid (HA) is an endogenous skin matrix component with moisturizing and anti-inflammatory and healing properties. Cosmetic formulations containing HA aim to enhance skin structure, hydrate skin and reduce wrinkles. Therefore, the skin diffusion of HA into stratum corneum after application of a formulation containing two different size of HA, High Molecular weight (HMW-HA) and Low Molecular Weight (LMW-HA)) was evaluated. Ex vivo human skin samples were used to validate an ELISA assay measuring HA in the stratum corneum (SC), viable epidermis and dermis, and to identify optimal washing and extraction methods. These methods were used to measure HA levels in the SC of subjects before and after daily topical application of an HA-containing formulation for 7 days. Samples of SC (5 tape strips) were taken before and 2 h after the application on D0, D1 and D7. The ELISA assay was suitable for measuring HA in the SC but not epidermal or dermal layers. The upper and lower limits of quantitation were the same for both sizes of HA (200 and 3.1 ng/ml, respectively). In both ex vivo human skin and human volunteers, the “dry method” of removing the formulation led to much higher levels of HA in the SC samples, whereas the “wet method” involving one cotton swab soaked with an aqueous solution containing 10% soap and a second cotton swab for drying, was effective in removing the formulation and more relevant to simulate washing/showering. In the clinical study, the amount of HA in SC layers 3–5 were used to represent the HA level in the SC, whereas layers 1 and 2 were considered as surface “residual film”. After each application, there was a significantly higher amount of HA compared to the amount before application, which was observed using both wash methods. The residual level 24 h after the first application was at least 8 times higher than before the first application and at least 31 times higher after 7 applications. In conclusion, these investigations validated the use of the ELISA method for the measurement of HA in SC samples. The ex vivo experiments provided recommendations for the clinical study, including the preferred cleansing and optimal sampling methods. The clinical study demonstrated the diffusion, accumulation and maintenance of HA levels in the SC after repeated application of the formulation containing HMW-HA and LMW-HA.

The deleterious effect of xylene-induced ear edema in rats: Protective role of dexketoprofen trometamol transdermal invasomes via inhibiting the oxidative stress/NF-κB/COX-2 pathway

Pain and inflammation could have a negative impact on a patient's quality of life and performance, causing them to sleep less. Dexketoprofen trometamol (DKT) is a water-soluble, nonselective NSAIDs. Because DKT is quickly eliminated in the urine after oral delivery, its efficacy is limited and must be taken repeatedly throughout the day. The main ambition of this work is to develop and characterize the potential of invasomes to enhance the transdermal transport of DKT to achieve efficient anti-inflammatory and pain management. The optimum formulation (C1) showed the least %RE (53.29 ± 2.68 %), the highest %EE (86.51 ± 1.05 %), and spherical nanosized vesicles (211.9 ± 0.57 nm) with (PDI) of 0.353 ± 0.01 and (ZP) of −19.15 ± 2.45 mV. DKT flux and deposition in stratum corneum, epidermal, and dermal skin layers were significantly augmented by 2.6 and 3.51 folds, respectively, from the optimum invasomal gel formulation (C1-G) compared to DKT conventional gel (DKT-G). The anti-inflammatory activity of C1-G was evaluated using a model of xylene-induced ear edema in rats. Xylene exposure upregulated the ear expression of COX-2 level and MPO activity. Xylene also significantly increased the ear NF-κB p65, TNF-α, IL-Iβ, and MDA levels. Furthermore, xylene induced oxidative stress, as evidenced by a significant decrease in ear GSH and serum TAC levels. These impacts were drastically improved by applying C1-G compared to rats that received DKT-G and plain invasomal gel formulation (plain C1-G). The histopathological findings imparted substantiation to the biochemical and molecular investigations. Thereby, C1-G could be a promising transdermal drug delivery system to improve the anti-inflammatory and pain management of DKT.

Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches.

The delivery of drugs via transdermal routes is an attractive approach due to ease of administration, bypassing of the first-pass metabolism, and the large skin surface area. However, a major drawback is an inability to surmount the skin's stratum corneum (SC) layer. Therefore, techniques reversibly modifying the stratum corneum have been a classical approach. Surmounting the significant barrier properties of the skin in a well-organised, momentary, and harmless approach is still challenging. Chemical permeation enhancers (CPEs) with higher activity are associated with certain side effects restricting their advancement in transdermal drug delivery. Furthermore, complexity in the interaction of CPEs with the skin has led to difficulty in elucidating the mechanism of action. Nevertheless, CPEs-aided transdermal drug delivery will accomplish its full potential due to advancements in analytical techniques, synthetic chemistry, and combinatorial studies. This review focused on techniques such as drug-vehicle interaction, vesicles and their analogues, and novel CPEs such as lipid synthesis inhibitors (LSIs), cell-penetrating peptides (CPPs), and ionic liquids (ILs). In addition, different types of microneedles, including 3D-printed microneedles, have been focused on in this review.

Transdermal Patches Approach Towards Self-Nano-Emulsifying Drug Delivery System (SNEDDS) Using Essential Oil as Penetration Enhancer

Abstract: A transdermal patch is a topically applied adhesive patch that delivers a medication dose directly into the blood. The patch allows for the safe delivery of a drug to the targeted site, ideally by a permeable layer covering a reservoir of the drug by melting small patches of drug embedded in the adhesive, which is one benefit of transdermal drug delivery over most types of pharmaceutical deliveries, including oral, topical, intramuscular, intravenous, and several others. This can also help heal a damaged body part, improving patient compliance, treatment efficacy, and dose frequency while minimizing the side effects. This review covers the production, methods of evaluation, quality, use of penetration enhancers, and pros and downsides of transdermal patches, as well as the benefits of essential oil as a penetration enhancer. Compared to chemical enhancers, essential oils have shown the ability to break down the stratum corneum layer, allowing drugs to penetrate deeper into the skin. Essential oils are excellent penetration enhancers for the skin. These penetration enhancers are cost-effective, biocompatible, readily available, non-toxic, chemically modifiable, and possibly biodegradable. In this review, attention has been paid to the formulation and evaluation of transdermal patches with the help of SNEDDS (self-nano-emulsifying drug delivery systems) using essential oil as a penetration enhancer, and their future prospects.

EVALUATING THE IMPACT OF SOLID MICRONEEDLES ON THE TRANSDERMAL DRUG DELIVERY SYSTEM FOR Ɣ-ORYZANOL

Objective: This study's goals were to develop a minimally invasive array of biocompatible polymeric solid microneedles and formulate a transdermal patch of drug Ɣ-Oryzanol as per poke and patch technology. Methods: Scanning electron microscopy was used to analyse the morphology of the solid microneedle arrays, which were created using a stereolithography (SLA) printer with high-resolution capabilities (25 and 140 microns for the z and x axes, respectively). Transdermal Patches of Ɣ-Oryzanol were formulated and evaluated for various characterization parameters. Further, the produced microneedle-transdermal drug delivery system of Ɣ-Oryzanol was examined for microneedle insertion skin and permeation of the drug across the porcine skin. Results: Solid microneedle arrays were manufactured using biocompatible Class I Dental SG resin having dimensions of 600 µm height and 300 µm width with tip diameters of 30 µm and 1.85 mm interspacing (Distance from tip to tip) and they were strong enough to penetrate porcine skin to a depth of 381.356 µm crossing the stratum corneum layer without causing any structural changes. Transdermal patches containing Ɣ-Oryzanol were formulated using different ratios of HPMC: Eudragit E-100. Good, consistent, and transparent films were formulated when the thickness of the film ranges between 0.516±0.25-0.628±0.21 mm, average weights ranged from 168.23±2.61to171.22±1.25(10/cm2), folding endurance ranged in between 10 folds to 12 folds for all the formulations with tensile strength lie between the 0.365 kg/mm2 to 0.465 kg/mm2. All the formulations showed good drug content between 99.3±0.06%-90.4±1.64% with 100% flat surfaces. Moisture content was found in the range of 2.012±0.013 to 4.213±0.031. Drug permeation studies reveal that compound Ɣ-Oryzanol transdermal patches didn’t show significant permeation across porcine skin (4.802.25 g/cm2) without piercing with microneedles while after poking skin using microneedles (74.502.35 g/cm2) drug showed good penetration properties. It was found that the amount of drug delivered increased to 44.251.57 g/cm2 at 2 min, which was 14.502.35 g/cm2 at 1 min to 4 min 74.502.35 g/cm2. Conclusion: Successful preparation of the Microneedle-Transdermal drug delivery system of Ɣ-Oryzanol and their evaluation indicated that the quality and consistency of the formulated preparation were excellent. With advantages in terms of lowered dose frequency, better patient compliance, and bioavailability, this may find use in the therapeutic field.

EHDA engineering of Piroxicam-PVP components for pharmaceutical dosages

This study aimed to prepare piroxicam loaded polyvinyl pyrollidone (PVP) particulate mat, fabricated mat incorporated tablets and coated polyvinyl alcohol (PVA) films. The mat, engineered by using electrohydrodynamic atomisation (EHDA) technique, was evaluated for morphological features and particle size using scanning electron microscopy. In vitro drug release, ex vivo skin permeation and in vivo anti-inflammatory studies of oral (i.e., tablets) and topical (i.e., films) dosage forms were conducted to assess the efficiency of prepared formulations. The EHDA processed piroxicam-PVP components exhibited spherical shape, uniform surface and particle size of 3.67 ± 0.70 μm. The piroxicam mat incorporated oral and coated topical formulations exhibited release percentage of 73.79 ± 1.9% and 80.11 ± 2.3% respectively over a time period of 180 min. During ex vivo permeation study, treatment of rat skin using 500 μm microneedles led to a higher permeation of piroxicam (from coated films i.e., 75.54 ± 2.2% as compared to unpierced skin i.e., 58.23 ± 2.7% with a gradient of 0.28 and 0.21 respectively within 240 min. During in vivo anti-inflammatory study, a 52.58 ± 3.2% decrease in paw inflammation was observed in mat incorporated tablets administered group within 360 min. In comparison, topical application of coated films led to a 67.28 ± 2.9% decrease in inflammation. Microneedle treatment followed by topical application of coated films resulted in an 81.43 ± 3.1% reduction in paw inflammation over 360 min. Micropiercing of the skin resulted in breaching of uppermost skin barrier layer stratum corneum leading to an increased piroxicam permeation and rapid therapeutic response. It was concluded that EHDA processed mat incorporated tablets and coated topical films can serve as a promising choice for improving the solubility of poorly soluble piroxicam and oral/topical anti-inflammatory therapy.

Arginine-based surfactants alter the rheological and in-plane structural properties of stratum corneum model membranes

HypothesisAmino acid-based surfactants have been proposed as skin permeation enhancers. In this work, we investigated the potentiality of two arginine-based amphiphiles as permeation enhancers by studying their interaction with stratum corneum (SC) model lipid membranes. ExperimentsNα-benzoyl arginine decyl- and dodecylamide were tested in comparison with the classical enhancer, oleic acid, and the non-enhancer, stearic acid. Two complementary approaches were used: lipid monolayers, taken as models of the unit film layer of SC, and atomistic molecular dynamics simulations. FindingsThe arginine-based amphiphiles studied were able to be incorporated into the SCM membrane and alter its rheological and structural properties by disordering the lipid chains, enhancing membrane elasticity, and thinning the overall membrane. They also affected the lateral structure of heterogeneous SC membranes at the nanoscale by relaxing and rounding the domain borders. Our work shows that the alteration observed of the overall rheological and structural properties of the SC membranes appears to be a shared ability for several amphiphilic permeation enhancers. Our results encourage future exploration of those amphiphiles as skin permeation enhancers.

Synchrotron-based infrared microspectroscopy of polymeric nanoparticles and skin: Unveiling molecular interactions to enhance permeation

The application of nanoparticles as permeation enhancers in skin drug delivery is a growing research field. However, the mechanisms of nanoparticles’ interaction with the skin structure are still unknown. Fucoidan/chitosan nanoparticles have demonstrated several physicochemical and biological advantages, among which is the enhancement of skin permeation. This study aims to elucidate permeation enhancement mechanisms using synchrotron-based Fourier Transform Infrared Microspectroscopy (SR-FTIRM) combined with multivariate analysis and in vitro skin permeation assay. Given the molecular weight influence on chitosan’s properties, the nanoparticles-skin interactions were evaluated with nanoparticles produced using low- and medium-molecular-weight chitosan. Chemical maps and spectral analysis revealed that fucoidan/chitosan nanoparticles induced changes in the lipids and protein regions. Inter-sample spectral differences were identified using principal component analysis. Low molecular weight fucoidan/ chitosan nanoparticles caused changes in the skin lipids’ lateral packing and structure at the stratum corneum layer towards a less ordered state and higher fluidity, and no evidence was found on proteins structure. The opposite was revealed for medium molecular weight fucoidan/chitosan nanoparticles, which induced changes in the secondary structure of keratin and altered lipid structure to an ordered and dense conformation. In vitro permeation assays with Franz diffusion cells correlate with the observed changes in the skin lipid and protein structure with enhanced skin permeation of a hydrophilic molecule incorporated within the fucoidan/chitosan nanoparticles. The findings of this study unveil molecular changes in the skin structure induced by the nanoparticles only possible with the application of the powerful and precise SR-FTIRM technique. This knowledge allows the design of nanoparticles towards an internalization pathway determining their fate within the skin structure.

Effects of excessive urea on rumen morphology and microbiota in Jianzhou Da'er goat (Capra hircus)

Urea is frequently used as a protein supplement in ruminant diets, but if used improperly, it can easily result in urea poisoning. The purpose of this study was to explore the effects of excessive urea feeding on rumen pathology and microbial diversity of the Jianzhou Da'er goat (Capra hircus). In this study, 9 male Jianzhou Da'er goats with an average weight of 22.9 kg were randomly divided into the control group (0% urea), 5% urea group and 10% urea group (dry matter basis, 3 goats per group). Morphological differences of rumen tissues were analyzed by Hematoxylin-Eosin staining and Prussian blue staining, and rumen microorganisms differences were analyzed by 16S rDNA sequencing on the Illumina Novaseq platform. Histopathological analysis showed that the length of rumen papilla in the 5% urea and 10% urea groups were shortened compared to the control group, and the thickness of the stratum corneum and muscular layer were significantly thinned (P < 0.05). 16S rRNA sequencing analysis indicated that microbial richness and diversity were significantly lower in goats fed on 5% urea or 10% urea, the abundance of Prevotella ruminicola was significantly decreased (P < 0.05), and the abundance of Ruminobacter amylophilus was significantly increased (P < 0.05), as compared with the control group. This study indicated that feeding 5% and 10% urea could damage rumen tissue morphology. Feeding 10% urea significantly reduced rumen microbial diversity and the abundance of Prevotella ruminicola, but increased the abundance of Ruminobacter amylophilus.