Skin Barrier Properties Research Articles

Development and Characterization of Film-Forming Solution Loaded with Syzygium cumini (L.) Skeels for Topical Application in Post-Surgical Therapies.

Considering the antioxidant and antimicrobial properties attributed to compounds in Syzygium cumini extract, this research aimed to advance postoperative therapeutic innovations. Specifically, the study assessed the physicochemical properties of a film-forming solution (FFS) incorporated with S. cumini, evaluating its therapeutic potential for postoperative applications. The S. cumini extract was meticulously characterized to determine its chemical composition, with particular emphasis on the concentration of phenolic compounds. Antioxidant and antimicrobial assays were conducted to assess the extract's efficacy in these domains. Following this, an FFS containing S. cumini was formulated and evaluated comprehensively for skin adhesion, mechanical and barrier properties, and thermal behavior. The antioxidant and antimicrobial activities of the S. cumini extract demonstrated promising results, indicating its potential utility as an adjunct in postoperative care. The developed FFS exhibited favorable physicochemical properties for topical application, including adequate skin adhesion and appropriate pH levels. Moreover, chemical and thermal analyses confirmed the formulation's stability and the retention of the extract's beneficial properties. Overall, the findings suggest that the S. cumini-loaded FFS holds significant potential as a valuable therapeutic tool for post-surgical management.

Changes in skin barrier over the first four days of life: a cross-sectional study.

We aimed to evaluate the trajectory of skin barrier properties in full-term newborns during the first four days after birth. Based on the MKNFOAD cohort (NCT02889081), transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, volar forearm, abdomen, and dorsal lower leg) were examined once within 96 h after birth in 384 full-term infants. Multivariable linear regression analysis was performed to assess variations in these skin barrier parameters with age adjusted for gestational age, neonate's sex, parents' allergy history, delivery mode, amniotic fluid characteristics, and birth weight. The regression coefficient (ß) and 95% confidence interval were reported. We analyzed a total of 384 neonates including 198 (51.6%) boys. TEWL values remained stable and showed no significant association with age (days). pH values exhibited a declining trend with age (p for trend <0.001). Both SCH values and sebum content grew with age (p for trend <0.001). During the first four days after birth, the skin TEWL remained stable, pH decreased, and the SCH and sebum content increased over time. These findings provide insights into the neonatal skin physiological development at the beginning of life. From birth to 96 h, TEWL was stable, pH showed a steep decline, SCH and sebum content increased. This study provides the first evidence of skin adaptation in the newborn due to changes in utero to after birth in the first 4 days of life in an Asian population. These findings will provide a new theoretical basis for neonatal skin physiology and clinical strategies for guiding newborn skin care.

Biophysical and permeability characterization of lyophilized (freeze-dried) human cadaver skin

The in vitro permeation testing (IVPT) of topical products is performed across the human cadaver skin, which is stored frozen for a prolonged duration. The cryo-preservation technique is not economical and is a cumbersome process. Moreover, prolonged skin preservation in a frozen state and frequent freeze-thawing are known to affect the integrity of the skin barrier. Therefore, lyophilization was explored as an alternative to protect the skin tissue from microbial contamination and degeneration. Notably, the project's objective was to investigate the impact of the freeze-drying process on the skin's barrier properties. The morphometrics of the lyophilized skin were measured. Histological studies did not reveal any notable changes in the organization and intactness of the layers due to the freeze-drying process. The biophysical attributes of the skin, such as transepidermal water evaporation rate and transepidermal electrical resistivity (TEER), were not significantly different between the control skin (not subjected to the freeze-drying process) and the freeze-dried skin (FDS). The permeability of caffeine, a hydrophilic model permeant, and nicotine, a lipophilic model permeant, were consistent across the control and the FDS. It is evident from the studies that the lyophilization process did not significantly impact the barrier properties and permeability of the skin.

Evaluating the effect of moisturizers containing endogenous lipids on skin barrier properties

Lipids in stratum corneum are largely responsible for skin barrier function. There have been numerous studies on skin barrier repairing and moisturizing effects of products containing occlusives, emollients and humectants. However, currently there are few studies systematically evaluating effect of moisturizers containing endogenous lipids on skin barrier properties. The objective of this study was to study the effect of products containing endogenous lipids on various barrier-related indicators. A total 89 subjects with dry skin were enrolled. To evaluate the effect of the test products on skin barrier function and hydration after 28 days of use on the face, this study combined clinical assessments of skin condition (skin redness, global appearance of dry line, skin roughness and radiance), instrumental assessments (transepidermal water loss, skin hydration and scaliness) and photo tracking (VISIA-CR,VC20 and 3D in-vivo Reflectance Confocal Microscope). Adverse reactions were also assessed. All test products showed significant improvement in all the attributes assessed by both clinical assessments and instrumental assessments after 28 days of treatment. In addition, the products containing skin-identical ceramides and niacinamide show improvement on TEWL and skin hydration. Two products containing exogenous lipids can improve skin hydration and barrier function which have demonstrated efficacy in improving dry skin condition.

Analysis of Correlation between Electron Diffraction Images of Corneocytes and Skin Barrier Properties by Multilayer Perceptron and Convolutional Neural Network

Analysis of Correlation between Electron Diffraction Images of Corneocytes and Skin Barrier Properties by Multilayer Perceptron and Convolutional Neural Network

Laser-mediated Solutions: Breaking Barriers in Transdermal Drug Delivery.

Skin diseases pose challenges in treatment due to the skin's complex structure and protective functions. Topical drug delivery has emerged as a preferred method for treating these conditions, offering localized therapy with minimal systemic side effects. However, the skin's barrier properties frequently limit topical treatments' efficacy by preventing drug penetration into deeper skin layers. In recent years, laser-assisted drug delivery (LADD) has gained attention as a promising strategy to overcome these limitations. LADD involves using lasers to create microchannels in the skin, facilitating the deposition of drugs and enhancing their penetration into the target tissue. Several lasers, such as fractional CO2, have been tested to see how well they work at delivering drugs. Despite the promising outcomes demonstrated in preclinical and clinical studies, several challenges persist in implementing LADD, including limited penetration depth, potential tissue damage, and the cost of LADD systems.Furthermore, selecting appropriate laser parameters and drug formulations is crucial to ensuring optimal therapeutic outcomes. Nevertheless, LADD holds significant potential for improving treatment efficacy for various skin conditions, including skin cancers, scars, and dermatological disorders. Future research efforts should focus on optimizing LADD techniques, addressing safety concerns, and exploring novel drug formulations to maximize the therapeutic benefits of this innovative approach. With continued advancements in laser technology and pharmaceutical science, LADD has the potential to revolutionize the field of dermatology and enhance patient care.

Effect of a low‐mineralized thermal spring water on skin barrier mechanical properties using atomic force microscopy

AbstractThe mineral content of thermal spring water (TSW) applied to the skin surface can directly influence the skin barrier. Indeed, our previous study showed that Avène TSW (ATSW), a low mineral content thermal spring water, protects the stratum corneum from dehydration compared to a mineral‐rich TSW (MR‐TSW) and maintains skin surface ultrastructure. While many TSWs have been recognized to have beneficial effects on skin, little is known about their localized and specific effects on skin barrier biomechanics at the nanometric scale. The aim of this study was to compare the effects of ATSW with a reference, MR‐TSW, on the biomechanical barrier properties of the skin under homeostasis conditions using atomic force microscopy (AFM). AFM was used to obtain a precise nanomechanical mapping of the skin surface after three applications of both TSW. This provides specific information on the skin topographical profile and elasticity. The topographic profile of skin samples showed a specific compaction of the skin layers after application of MR‐TSW, characterized by an increase of the total number of external skin layers, compared to non‐treated samples. By contrast, ATSW did not modify the skin topographic profile. High‐resolution force/volume acquisitions to capture the elastic modulus showed that it was directly correlated with skin rigidity. The elastic modulus strongly and significantly increased after MR‐TSW application compared to non‐treated skin. By contrast, applications of ATSW did not increase elastic modulus. These data demonstrate that applications of MR‐TSW significantly modified skin barrier properties by increasing skin surface layer compaction and skin rigidity. By contrast, ATSW did not modify the topographical profile of skin explants nor induce mechanical stress at the level of the stratum corneum, indicating it does not disrupt the biophysical properties linked to skin surface integrity.

Role of cholinergic agonists &amp; hyperthermia on regional skin barriers: exposure science implications

Regional differences in skin barrier properties are common in mammals, as some exterior surfaces are fairly impermeable and others are leakier. Neural-induced changes in skin physiology and temperature have the potential to alter skin barrier properties, but the circumstances and mechanisms are unclear. We hypothesized that increasing methylcholine (MCh) or acetylcholine (ACh) concentration would decrease the transepithelial resistance (an index of the skin barrier) measured across mouse paw pad skin jacketed at neutral skin (32°C) or internal (37°C) temperature. Additionally, we hypothesized that paw pads would have lower transepithelial resistance compared to mouse tail skin, and subjecting samples to 40°C (local cutaneous heat stress) would lower transepithelial resistance compared to paw pad skin tested at 32°C. 30 C57BL/6 mouse rear paw pads (containing sweat glands) and 7 mouse tail skins (no sweat glands) were dissected and mounted into a vertical Ussing chamber filled with Kreb’s bicarbonate buffer, gassed with 95% O₂ &amp; 5% CO₂, and encased in a temperature jacket. Transepithelial resistance utilized a current clamp and was measured with Ag-AgCl2 electrodes placed in both epidermal and hypodermal baths during hypodermal-side-only cholinergic dosing (5 min/dose). ACh (0, 0.0833, 0.1666, 0.2499, 0.4166, 0.58323, and 0.74989 M) significantly decreased transepithelial resistance in paw pads clamped at 37°C in a dose-dependent manner. Tail skin had significantly higher transepithelial resistance than paw pad skin. However, transepithelial resistance decreased significantly with MCh (same dosing as ACh) at both skin sites. Increasing jacket temperature to 40°C did not alter the magnitude of decrease in transepithelial resistance to MCh in paw pads compared to 32°C. Transepithelial resistance observations were similar when data were expressed as absolute or relative changes to baseline. Increased ion movement in murine skin (signifying a leakier epithelium) occurred with cholinergic stimulation but not with local hyperthermia, suggesting that neural influences can suffciently affect skin function to directly alter regional skin barriers. P30ES026529 with additional support from TL1TR001997 and R25ES027684. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Protective effect of soy germ-fermented postbiotics derived from Lacticaseibacillus paracasei DCF0429 (SGPB-DCF0429) in human reconstituted skin

Postbiotics are non-viable microorganisms and their components that provide health benefits to their hosts. At this time, the potential effects of food-based postbiotics have not been reported. This study was designed to isolate lactic acid bacteria (LAB) from traditional Korean fermented foods and to evaluate the beneficial properties of soy germ-fermented postbiotics produced using LAB in a reconstructed epidermis model. Among the LABs isolated from traditional Korean fermented foods, Lacticaseibacillus paracasei DCF0429 showed the highest antioxidant and β-glucosidase activities without any harmful enzyme activities. Additionally, L. paracasei DCF0429 increased the isoflavone aglycone content and antioxidant activity of soy germ during postbiotic production. Finally, the soy germ-fermented postbiotic DCF0429 (SGPB-DCF0429) was investigated for its skin barrier properties. SGPB-DCF0429 protected epidermis tissue against oxidative stress by increasing the cell viability and regulating pro-inflammatory cytokines. These results suggest that SGPB-DCF0429 could serve as a promising protective effect in oxidative stress-induced epidermis tissue.

Lespedeza maximowiczii flower absolute promotes skin epithelization, barrier properties, and moisturization-related beneficial responses in human keratinocytes

Lespedeza maximowiczii (LM), a member of the legume family, has tyrosinase inhibitory and estrogenic activities. However, its effects on skin-related biological activities remain unclear. Therefore, the present study aimed to explore the effects of LM flower absolute (LMFAb) on skin-related biological events, especially skin re-epithelization, barrier and moisturizing-related keratinocyte (HaCaT cell) responses. In this study, LMFAb was isolated from LM flowers via solvent extraction and its chemical composition analysis was performed using gas chromatography/mass spectrometry. 5-bromo-2′-deoxyuridine incorporation, Boyden chamber, sprout outgrowth, enzyme-linked immunosorbent, and Western blot assay were used to analyze the biological effects of LMFAb on HaCaT cells (a human epidermal keratinocyte cell line). Twelve components were identified in LMFAb. LMFAb promoted cell proliferation, migration, and sprout outgrowth in HaCaT cells. The absolute enhanced the activations of MAPKs (ERK1/2, JNK, and p38), PI3K and AKT proteins in HaCaT cells and elevated collagen type I and IV levels in HaCaT cell conditioned medium. In addition, LMFAb induced an increase in the expression levels of epidermal barrier proteins (filaggrin and involucrin) in HaCaT cells. Furthermore, LMFAb increased hyaluronan (HA) production and expression of HA synthases (HAS-1, HAS-2, and HAS-3) but decreased HYBID (HA binding protein involved in HA depolymerization) level in HaCaT cells. These findings demonstrate that LMFAb might promote skin re-epithelization, barrier and moisturizing-related beneficial responses in keratinocytes. This study suggests that LMFAb should be considered a potential starting material for the development of cosmetic or pharmaceutical agents that restore the functions of damaged skin.

Advances in Transdermal Delivery of Antimicrobial Peptides for Wound Management: Biomaterial-Based Approaches and Future Perspectives.

Antimicrobial peptides (AMPs), distinguished by their cationic and amphiphilic nature, represent a critical frontier in the battle against antimicrobial resistance due to their potent antimicrobial activity and a broad spectrum of action. However, the clinical translation of AMPs faces hurdles, including their susceptibility to degradation, limited bioavailability, and the need for targeted delivery. Transdermal delivery has immense potential for optimizing AMP administration for wound management. Leveraging the skin's accessibility and barrier properties, transdermal delivery offers a noninvasive approach that can circumvent systemic side effects and ensure sustained release. Biomaterial-based delivery systems, encompassing nanofibers, hydrogels, nanoparticles, and liposomes, have emerged as key players in enhancing the efficacy of transdermal AMP delivery. These biomaterial carriers not only shield AMPs from enzymatic degradation but also provide controlled release mechanisms, thereby elevating stability and bioavailability. The synergistic interaction between the transdermal approach and biomaterial-facilitated formulations presents a promising strategy to overcome the multifaceted challenges associated with AMP delivery. Integrating advanced technologies and personalized medicine, this convergence allows the reimagining of wound care. This review amalgamates insights to propose a pathway where AMPs, transdermal delivery, and biomaterial innovation harmonize for effective wound management.

Effect of L-4-Thiazolylalanine (Protinol™) on skin barrier strength and skin protection.

Skin barrier properties are critical for maintaining epidermal water content, protecting from environmental factors and providing the first line of defense against pathogens. In this study, we investigated the non-proteinogenic amino acid L-4-Thiazolylalanine (L4) as a potential active ingredient in skin protection and barrier strength. L4 on wound healing, anti-inflammatory and anti-oxidant properties were evaluated using monolayers and 3D skin equivalents. The transepithelial electrical resistance (TEER) value was used in vitro as a strong indicator of barrier strength and integrity. Clinical L4 efficacy was assessed for the evaluation of the skin barrier integrity and soothing benefits. In vitro treatments of L4 show beneficial effects in wound closure mechanism, and we demonstrate that L4 anti-oxidant benefits with markedly increased HSP70 and decreased reactive oxygen species production induced by UVs exposure. Barrier strength and integrity were significantly improved by L4, confirmed clinically by an increase in 12R-lipoxygenase enzymatic activity in the stratum corneum. In addition, soothing benefits of L4 have been shown clinically with the decrease in redness after methyl nicotinate application on the inner arm and the significant reduction of the erythema and the skin desquamation on the scalp. L4 delivered multiple skin benefits by strengthening the skin barrier, accelerating the skin repair process as well as soothing the skin and the scalp with anti-inflammaging effects. The observed efficacy validates L4 as a desirable skincare ingredient for topical treatment.

Racial and Ethnic Variations in Skin Barrier Properties and Cultural Practices in Skin of Color Newborns, Infants, and Children.

The skin of newborns and infants of all races/ethnicity is more susceptible to skin barrier disruption than adult skin. This consensus paper offers insights into potential skincare implications for using gentle cleansers and moisturizers for skin of color (SOC) newborns, infants, and children. Six pediatric dermatologists and dermatologists used a Delphi communication technique to adopt 5 statements for SOC newborns, infants, and children on skin barrier integrity and the importance of skin care to promote a healthy skin barrier.&nbsp; Results: Regardless of ethnicity, newborn and infant skin is still developing and more susceptible to infections and chemical and thermal damage. A growing body of evidence supports skincare starting early in life, recognizing that the ongoing daily use of gentle cleansers and moisturizers containing barrier lipids, such as ceramides, promotes a healthy skin barrier. Understanding cultural differences in everyday skincare practices for SOC newborns, infants, and children is critical for developing an evidence base to substantiate skincare practices.&nbsp; Conclusions: Closing knowledge gaps in the clinical presentation, cultural differences, and approach to treating skin conditions using skincare for SOC newborns, infants, and children may improve patient outcomes.&nbsp;&nbsp; Schachner&nbsp; LA, Andriessen A, Benjamin&nbsp; L, et al. Racial/ethnic variations in skin barrier properties and cultural practices in skin of color newborns, infants and children. J Drugs Dermatol. 2023;22(7):657-663. doi:10.36849/JDD.7305.

Elegant, Flexible Vesicular Nanocarriers for the Efficient Skin Delivery of Topically Applied Drugs

Background: Skin diseases represent a major health concern worldwide and negatively impact patients’ quality of life. Despite the availability of various efficacious drugs, their therapeutic outcome is often limited due to shortcomings related to the formidable skin barrier and unfavorable physicochemical properties of drugs. Flexible nano-vesicles have shown tremendous potential to overcome these hurdles and improve the local therapeutic effect of these drugs. Objective: This review article is aimed to shed light on flexible nano-vesicular carriers as a means to combat skin diseases. Methods: The literature was reviewed using PubMed database using various keywords such as liposomes, flexible (deformable liposomes) (transferosomes), ethosomes, transethosomes, niosomes, and spanlastics. Results: Liposomes and niosomes were found effective for the loading and release of both hydrophilic and lipophilic drugs. However, their limited skin penetration led to drug delivery to the outermost layers of skin only. This necessitates the search for innovative vesicular carriers, including liposomes, flexible (deformable liposomes), ethosomes, transethosomes, and spanlastics. These flexible nano-vesicular carriers showed enhanced drug delivery and deposition across various skin layers, which was better than their corresponding conventional vesicles. This resulted in superior drug efficacy against various skin diseases such as skin cancer, inflammatory skin diseases, superficial fungal infections, etc. Conclusion: Flexible nano-vesicular carriers have proven themselves as efficient drug delivery systems that are able to deliver their cargo into the deep skin layers and thus, improve the therapeutic outcome of various skin diseases. However, there remain some challenges that need to be addressed before these nanocarriers can be translated from the lab to clinics.

Efficacy of the Radical Scavenger, Tempol, to Reduce Inflammation and Oxidative Stress in a Murine Model of Atopic Dermatitis.

Atopic dermatitis (AD) is the most common chronically relapsing inflammatory skin disease, predominantly common in children; it is characterized by an eczematous pattern generally referable to skin dryness and itchy papules that become excoriated and lichenified in the more advanced stages of the disease. Although the pathophysiology of AD is not completely understood, numerous studies have demonstrated the complex interaction between genetic, immunological, and environmental factors, which acts to disrupt skin barrier function. Free radicals play a key role by directly damaging skin structure, inducing inflammation and weakening of the skin barrier. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a membrane-permeable radical scavenger, known to be a stable nitroxide, which exhibits excellent antioxidant effects in several human disorders, such as osteoarthritis and inflammatory bowel diseases. Considering the few existing studies on dermatological pathologies, this study aimed to evaluate tempol, in a cream formulation, in a murine model of AD. Dermatitis was induced in mice via dorsal skin application of 0.5% Oxazolone, three times a week for two weeks. After induction, mice were treated with tempol-based cream for another two weeks at three different doses of 0.5%, 1% and 2%. Our results demonstrated the ability of tempol, at the highest percentages, to counteract AD by reducing the histological damage, decreasing mast cell infiltration, and improving the skin barrier properties, by restoring the tight junction (TJs) and filaggrin. Moreover, tempol, at 1% and 2%, was able to modulate inflammation by reducing the nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway, as well as tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression. Topical treatment also attenuated oxidative stress by modulating nuclear factor erythroid 2-related factor 2 (Nrf2), manganese superoxide dismutase (MnSOD), and heme oxygenase I (HO-1) expression levels. The obtained results demonstrate the numerous advantages provided by the topical administration of a tempol-based cream formulation, in reducing inflammation and oxidative stress through modulation of the NF-κB/Nrf2 signaling pathways. Therefore, tempol could represent an alternative anti-atopic approach to treating AD, thereby improving skin barrier function.

Microbial Surfactants to the Rescue

Microbial Surfactants to the Rescue

Evaluating the repetitive mucus extraction effects on mucus biomarkers, mucous cells, and the skin-barrier status in a marine fish model

Among all the mucosal barriers, the skin and its surrounding mucus are possibly the main defensive tool against changes in the environment that can be harmful for fish. Due to the extraction of this mucus being less invasive, the study of its production and functions has attracted great interest in recent years. However, there are still many gaps concerning the sampling process as well as the possible alterations in skin integrity and mucus composition. In the current study, the effects of skin mucus extraction were determined by comparing the effects of a single extraction (single extraction group, SEG) with those of three successive extractions separated by 3 days (repetitive extractions group, REG). Intact skin histology without mucus extraction (ØEG) and both plasma and skin mucus biomarkers and antibacterial capacities were also assessed. Regarding the skin histology and skin barrier properties, both the SEG and REG did not show differences in the intact skin. Interestingly, repetitive mucus extractions seemed to activate skin mucus turnover, significantly increasing the number of small-sized mucous cells (cell area&amp;lt; 100 µm2) and reducing the number of large-sized mucous cells (cell area &amp;gt; 150 µm2). Repetitive extractions significantly decreased the amounts of soluble protein and increased cortisol secretion. These metabolites remained unaltered in the plasma, indicating different responses in the plasma and mucus. Despite changes in the mucus biomarkers, antibacterial capacity against pathogenic bacteria (Pseudomonas anguilliseptica and Vibrio anguillarum) was maintained in both the plasma and mucus irrespective of the number of mucus extractions. Overall, the mucus sampling protocol had little effect on skin integrity and mucus antibacterial properties, only modifying the amounts of soluble protein exuded and stimulating mucous cell replacement. This protocol is a feasible and minimally invasive way of studying and monitoring fish health and welfare and can be used as an alternative or a complement to plasma analysis. This methodology can be transferred to farm culture conditions and be very useful for studying threatened species in order to preserve fish welfare.

Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders

Therapeutic aryl hydrocarbon receptor (AHR) modulating agents gained attention in dermatology as non-steroidal anti-inflammatory drugs that improve skin barrier properties. By exploiting AHR’s known ligand promiscuity, we generated novel AHR modulating agents by lead optimization of a selective AHR modulator (SAhRM; SGA360). Twenty-two newly synthesized compounds were screened yielding two novel derivatives, SGA360f and SGA388, in which agonist activity led to enhanced keratinocyte terminal differentiation. SGA388 showed the highest agonist activity with potent normalization of keratinocyte hyperproliferation, restored expression of skin barrier proteins and dampening of chemokine expression by keratinocytes upon Th2-mediated inflammation in vitro. The topical application of SGA360f and SGA388 reduced acute skin inflammation in vivo by reducing cyclooxygenase levels, resulting in less neutrophilic dermal infiltrates. The minimal induction of cytochrome P450 enzyme activity, lack of cellular toxicity and mutagenicity classifies SGA360f and SGA388 as novel potential therapeutic AHR ligands and illustrates the potential of medicinal chemistry to fine-tune AHR signaling for the development of targeted therapies in dermatology and beyond.

Effect of Heat Sealing and Storage on Mechanical and Barrier Properties of Maillard Modified Fish Skin Gelatin/L-arabinose Composite Films

The increasing accumulation of non-degradable plastic food packaging is a global concern. In this study, we aimed to optimize the heat-sealing process of fish skin gelatin/L-arabinose (FG-Ara) composite films modified by the Maillard reaction. The effects of storage temperature, humidity, and time on the mechanical and barrier properties of the modified FG-Ara composite films were investigated. The optimal heat-sealing parameters were 24 V, with vacuum, heat-sealing, and cooling times of 7.0, 3.0, and 3.0 s, respectively. After 120 days of storage at low temperatures (4, −17 °C), the tensile strength of the composite films decreased to 11.15 ± 1.64 and 13.14 ± 1.68 MPa, respectively, and the elongation at break increased by 39.07% and 18.29% compared with the initial value, respectively. Moreover, the water vapor permeability in the low-temperature treatment groups remained relatively stable at the initial stages of storage (0–40 days) and reached 39.57 ± 3.09 and 26.95 ± 18.50 g·mm/m2·d·kPa after 120 days, respectively. The milk powder packed in the FG-Ara composite films had good quality and no hardening in low-temperature environments. After 120 days of storage, the peroxide value of the soybean oil packed in the films still met the quality standard of first-grade soybean oil. Furthermore, the Arrhenius equation was used to fit the peroxide values of soybean oil at different temperatures. The maximum shelf life of soybean oil coated by the composite film was predicted to be 250 days. The experimental results demonstrated that the optimized films might serve as effective food packaging materials.

Proline, hydroxyproline, and pyrrolidone carboxylic acid derivatives as highly efficient but reversible transdermal permeation enhancers

Overcoming the skin barrier properties efficiently, temporarily, and safely for successful transdermal drug delivery remains a challenge. We synthesized three series of potential skin permeation enhancers derived from natural amino acid derivatives proline, 4-hydroxyproline, and pyrrolidone carboxylic acid, which is a component of natural moisturizing factor. Permeation studies using in vitro human skin identified dodecyl prolinates with N-acetyl, propionyl, and butyryl chains (Pro2, Pro3, and Pro4, respectively) as potent enhancers for model drugs theophylline and diclofenac. The proline derivatives were generally more active than 4-hydroxyprolines and pyrrolidone carboxylic acid derivatives. Pro2–4 had acceptable in vitro toxicities on 3T3 fibroblast and HaCaT cell lines with IC50 values in tens of µM. Infrared spectroscopy using the human stratum corneum revealed that these enhancers preferentially interacted with the skin barrier lipids and decreased the overall chain order without causing lipid extraction, while their effects on the stratum corneum protein structures were negligible. The impacts of Pro3 and Pro4 on an in vitro transepidermal water loss and skin electrical impedance were fully reversible. Thus, proline derivatives Pro3 and Pro4 have an advantageous combination of high enhancing potency, low cellular toxicity, and reversible action, which is important for their potential in vivo use as the skin barrier would quickly recover after the drug/enhancer administration is terminated.