Search Results (25)

This study investigates a noninvasive continuous glucose monitoring (NI-CGM) system optimized for earlobe application, leveraging the site’s anatomical advantages—absence of bone, muscle, and thick skin—for enhanced optical transmission. The system integrates multimodal sensing, combining near-infrared (NIR) diffuse transmission with temperature and pressure sensors. A novel Multi-Wavelength Slope Efficiency Near-Infrared Spectroscopy (MW-SE-NIRS) method is introduced, enhancing noise robustness through the slope efficiency-based parameterization of NIR signal dynamics. By employing three NIR wavelengths with distinct scattering and absorption properties, the method improves glucose detection reliability, addressing tissue heterogeneity and physiological noise in noninvasive monitoring. To validate the feasibility, a pilot clinical trial enrolled five participants with normal or pre-diabetic glucose profiles. Continuous glucose data capturing pre- and postprandial variations were analyzed using a 1D convolutional neural network (Conv1D). For three subjects under stable physiological conditions, the model achieved 97.0% Clarke error grid (CEG) A-Zone accuracy and a mean absolute relative difference (MARD) of 5.2%. Across all participants, results showed 90.9% CEG A-Zone accuracy and a MARD of 8.4%, with performance variations linked to individual factors such as earlobe thickness variability and physical activity. These outcomes demonstrate the potential of the MW-SE-NIRS system for noninvasive glucose monitoring and highlight the importance of future work on personalized modeling, sensor optimization, and larger-scale clinical validation. Full article

The rapid pace of modern life has contributed to a significant decline in sleep quality, which has become an urgent global public health issue. Melatonin, an endogenous hormone that regulates circadian rhythms, is vital in maintaining normal sleep cycles. While oral melatonin supplementation is widely used, transdermal delivery systems present advantages that include the avoidance of first-pass metabolism effects and enhanced bioavailability. In this study, a novel melatonin transdermal delivery system was successfully developed using a thermosensitive poly(N-vinylcaprolactam) [p(NVCL)]-based carrier. The p(NVCL) polymer was synthesized through free radical polymerization and characterized for its structural properties and phase transition temperature, in alignment with skin surface conditions. Orthogonal optimization experiments identified 3% azone, 3% menthol, and 4% borneol as the optimal enhancer combination for enhanced transdermal absorption. The formulation demonstrated exceptional melatonin loading characteristics with high encapsulation efficiency and stable physicochemical properties, including an appropriate pH and optimal moisture content. Comprehensive in vivo evaluation using normal mouse models revealed significant sleep quality improvements, specifically a shortened sleep latency and extended non-rapid eye movement sleep duration, with elevated serum melatonin and serotonin levels. Safety assessments including histopathological examination, biochemical analysis, and 28-day continuous administration studies confirmed excellent biocompatibility with no adverse reactions or systemic toxicity. Near-infrared fluorescence imaging provided direct evidence of enhanced transdermal absorption and superior biodistribution compared to oral administration. These findings indicate that the p(NVCL)-based melatonin transdermal gel system offers a safe, effective and convenient non-prescription option for sleep regulation, with promising potential for clinical translation as a consumer sleep aid. Full article

Objectives: This study aimed to identify and develop a novel, safe, and effective transdermal penetration enhancer derived from the leaves of Perilla frutescens (L.) Britt, and to explore the underlying mechanisms of its penetration enhancement effects. Methods: To evaluate the safety profile of the penetration enhancer, both skin irritation tests and histopathological analyses were conducted. The transdermal enhancement capabilities of the penetration enhancer were assessed in vitro using five model drugs. Furthermore, to gain insights into the penetration enhancement mechanism of this novel penetration enhancer, a range of analytical methods were used, including a spectroscopic technique, differential scanning calorimetry, micro-optical techniques, and molecular docking simulations. Results: Perilla essential oil contained 93.70% perilla ketone (PEK), which exhibited a safety profile superior to that of azone. PEK significantly increased the cumulative skin permeation of all the model drugs (p < 0.05). PEK exhibited the most obvious impact on puerarin penetration, with quantitative enhancement ratios of 2.96 ± 0.07 and 3.39 ± 0.21 at concentrations of 3% and 5% (w/v), respectively. A strong correlation between the enhancement effect of PEK and the physicochemical properties of the drugs was observed. Mechanistic studies revealed that PEK facilitates drug distribution from the solution phase to the stratum corneum (SC). Conclusions: PEK, seldom discussed in former studies, was observed to show extensive penetration enhancement effects by inducing conformational changes in SC lipids and disrupting the tightly ordered bilayer arrangement of lipids. These findings highlight the potential of PEK as a promising and safe natural transdermal penetration enhancer. Full article

Background/Objectives: Laurocapram (Azone) attracted attention 40 years ago as a compound with the highest skin-penetration-enhancing effect at that time; however, its development was shelved due to strong skin irritation. We had already prepared and tested an ante-enhancer (IL-Azone), an ionic liquid (IL) with a similar structure to Azone, consisting of ε-caprolactam and myristic acid, as an enhancer candidate that maintains the high skin-penetration-enhancing effect of Azone with low skin irritation. In the present study, fatty acids with different carbon numbers (caprylic acid: C8, capric acid: C10, lauric acid: C12, myristic acid: C14, and oleic acid: C18:1) were selected and used with ε-caprolactam to prepare various IL-Azones in the search for a more effective IL-Azone. Methods: Excised porcine skin was pretreated with each IL-Azone to assess the in vitro skin permeability of antipyrine (ANP) as a model penetrant. In addition, 1,3-butanediol was selected for the skin permeation test to confirm whether the effect of IL-Azone was due to fatty acids and if this effect differed depending on the concentration of IL-Azone applied. Results: The results obtained showed that C12 IL-Azone exerted the highest skin-penetration-enhancing effect, which was higher than Azone. On the other hand, many of the IL-Azones tested had a lower skin-penetration-enhancing effect. Conclusions: These results suggest the potential of C12 IL-Azone as a strong and useful penetration enhancer. Full article

Background/Objectives: Cyclovirobuxine D, a natural compound derived from the medicinal plant Buxus sinica, demonstrates a diverse array of therapeutic benefits, encompassing anti-arrhythmic properties, blood pressure regulation, neuronal protection, and anti-ischemic activity. However, its limited solubility hinders the bioavailability of current oral and injectable formulations, causing considerable adverse reactions and toxicity. Methods: In this investigation, we embarked on an unprecedented exploration of the skin penetration potential of cyclovirobuxine D utilizing chemical penetration enhancers and niosomes as innovative strategies to enhance its dermal absorption. These strategies were rigorously tested and optimized. Results: Among the tested chemical penetration enhancers, azone emerged as the most potent, achieving a 4.55-fold increase in skin penetration compared to the untreated group. Additionally, when encapsulated within niosomes, primarily composed of Span60 and cholesterol, the skin penetration of cyclovirobuxine D was notably enhanced by 1.50-fold. Furthermore, when both cyclovirobuxine D and azone were co-encapsulated within the niosomes, the skin penetration of cyclovirobuxine D was remarkably elevated by 8.10-fold compared to the solvent-dispersed group. This enhancement was corroborated through rigorous in vitro and in vivo experiments. Notably, the combination of other chemical penetration enhancers with niosome encapsulation also exhibited synergistic effects in enhancing the skin penetration of cyclovirobuxine D. Conclusions: These findings provide a compelling rationale for the administration of cyclovirobuxine D via skin-mediated transdermal delivery, offering superior safety, efficacy, and convenience. The innovative combination of niosomes and chemical penetration enhancers represents a novel system for the transdermal delivery of cyclovirobuxine D, holding immense promise for clinical applications in the treatment of brain, neuronal, and cardiovascular disorders. Full article

We developed a sustained-release transdermal drug delivery system (TDDS) containing simvastatin (SIM) and captopril (CAP) to treat hypertension and hyperlipidemia and overcome treatment drawbacks, including significant liver first-pass effects, low bioavailability, and the short half-life of SIM and CAP oral tablets. We used a transdermal diffusion meter to preselect the formula of the SIM-CAP TDDS. Based on in vitro permeation experiments, we optimized the formula of the SIM-CAP TDDS to include 24% SIM, 24% CAP, 34% polyvinyl alcohol (PVA), 16% oleic acid (OA)–azone, and 2% polyacrylic acid resin II. We evaluated the optimized SIM-CAP TDDS formula by its appearance, stability, stickiness, drug content, in vivo pharmacokinetics, and skin irritation tests. The results indicated that the patch had good stability and stickiness. The SIM and CAP contents were 5.02 ± 0.41 mg/cm² in the 1 cm² SIM-CAP TDDS. The pharmacokinetic results indicated that the system continuously released SIM and CAP for 24 h and significantly enhanced their bioavailability, with a higher area under the curve. The SIM-CAP TDDS exhibits a sustained-release effect with good characteristics and pharmacokinetics. And it is safe and has no irritating effects on the skin; therefore, it is an ideal formulation. Full article

Staphylococcus pseudintermedius (S. pseudintermedius) is the main pathogen causing pyoderma of canines. With the emergence of drug-resistant bacteria, traditional antibiotic treatments are limited. As a potential antibacterial agent, NZ2114 was effective against S. pseudintermedius, including drug-resistant strains. Its bactericidal efficacy was superior to mupiroxacin, ofloxacin and lincomycin. To facilitate the transcutaneous delivery of NZ2114 for the treatment of superficial pyoderma, chemical permeation enhancers were added since water-soluble NZ2114 does not easily penetrate the skin lipid layer. Two different NZ2114 sprays were prepared by combining 1% Azone + 10% propylene glycol (PG) or 5% N-methylpyrrolidone (NMP) + 10% PG with NZ2114 after screening. The cumulative permeability of NZ2114 sprays were 244.149 and 405.245 μg/cm² at 24 h with an in vitro percutaneous assay of mice skin, which showed a 244% and 405% increase in skin permeability than NZ2114, respectively. In addition, the efficacy of NZ2114 sprays in reducing skin bacteria colonisation was demonstrated in a mouse model of superficial pyoderma (24 mice, 3 mice/group) induced by S. pseudintermedius, and the 5% NMP + 10% PG + NZ2114 group had the best therapeutic effect compared to the other groups. This preparation did not cause any skin irritation, laying the foundation for the development of an effective and non-toxic topical product. Full article

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K_100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant. Full article

The Late Miocene palaeofloras of the La Cerdanya Basin represent a unique look into the Pyrenean Miocene forested areas of the Iberian Peninsula at a time when the European warm and humid climate was experiencing progressive cooling and aridification. Macrofossils (leaves, seeds, fruits and cones) and miospores from several outcrops revealed the composition and abundances of the different plant species present in the area during the Tortonian and early Messinian geological stages (ca. 11.1–5.7 Ma). These fossils were found in the sediment deposits of an ancient lake system situated in the southwestern part of the basin. Previous studies indicated the presence of highly diversified mixed mesophytic forests with broadleaved evergreen and deciduous trees and conifers. However, the spatial structure and distribution of these forest types remains unknown. In the present work, the biomization method was used to infer the different late Miocene vegetation types from the basin. The extent of these vegetation types was calculated using a methodology for mapping vegetation units from fossil and biome data. While previous attempts at mapping Miocene vegetation units had a broad geographical scale, the present work aimed to map the extent of the vegetation units at a small scale, recreating local and specific vegetation changes in an abrupt basin. Results showed similarly high scores between for four biome types, which represent the different types of vegetation that coexisted in the basin during the Tortonian and the early Messinian: warm-temperate evergreen broadleaf and mixed woodlands (WTEM biome), temperate deciduous forests (TEDE) and cool conifer forests (COMX and COEG). Their extent was depicted in two vegetation maps, which account for differences in palaeoaltitude and palaeoclimate. These forests occupied different vegetation belts, which shifted upwards and downwards with climatic variations and the progressive uplift of the Pyrenees during the late Miocene. Azonal riparian forests and wetland vegetation occupied the more humid areas in the centre of the basin. Nonetheless, dry conditions during the early Messinian and decrease in the lake area degraded the wetland environments, which were partially replaced by broadleaved evergreen mixed woodlands. Full article

Caspofungin is a drug that is used for fungal infections that are difficult to treat, including invasive aspergillosis and candidemia, as well as other forms of invasive candidiasis. The aim of this study was to incorporate Azone in a caspofungin gel (CPF-AZ-gel) and compare it with a promoter-free caspofungin gel (CPF-gel). An in vitro release study using a polytetrafluoroethylene membrane and ex vivo permeation into human skin was adopted. The tolerability properties were confirmed by histological analysis, and an evaluation of the biomechanical properties of the skin was undertaken. Antimicrobial efficacy was determined against Candida albicans, Candida glabrata, Candida parapsilosis, and Candida tropicalis. CPF-AZ-gel and CPF-gel, which had a homogeneous appearance, pseudoplastic behavior, and high spreadability, were obtained. The biopharmaceutical studies confirmed that caspofungin was released following a one-phase exponential association model and the CPF-AZ gel showed a higher release. The CPF-AZ gel showed higher retention of caspofungin in the skin while limiting the diffusion of the drug to the receptor fluid. Both formulations were well-tolerated in the histological sections, as well as after their topical application in the skin. These formulations inhibited the growth of C. glabrata, C. parapsilosis, and C. tropicalis, while C. albicans showed resistance. In summary, dermal treatment with caspofungin could be used as a promising therapy for cutaneous candidiasis in patients that are refractory or intolerant to conventional antifungal agents. Full article

Pollen and sediment data from a 10.5 m-deep alluvial exposure and a secondary tributary exposure at Upper Arroyo, a seasonal river, in Saltillo, Mexico, were examined with the aim of reconstructing the vegetation and environmental history during the Holocene as a whole. The role of climate change in Chihuahuan Desert flora development after 8800 BP was assessed, in addition to more local physiographic factors, such as erosion and accumulation, soil development and denudation, and hydrological entrenchment. Climate change appeared to have been a principal agent of vegetation change in the Early and Middle Holocene, with a periodic expansion of desert vegetation. A reduction in the environmental carrying capacities for mesophytic flora according to physiographic factors, such as soil erosion and channel entrenchment, was then identified after 2300 BP, also promoting azonal ecological niches for xerophytic vegetation in southern Coahuila, Mexico, that persist despite modern variations in precipitation. Full article

In this study, we developed a sustained-release transdermal delivery system containing losartan potassium (LP) and verapamil hydrochloride (VPH). LP and VPH have low bioavailability and long half-life. Therefore, the development of an optimum administration mode is necessary to overcome these drawbacks and enhance the antihypertensive effect. A transdermal diffusion meter was used to determine the optimal formulation of LP-VPH transdermal drug delivery systems (TDDS). Based on in vitro results, a sustained-release patch was prepared. Physical characteristics, including quality, stickiness, and appearance, were evaluated in vitro, while pharmacokinetics and skin irritation were evaluated in vivo. The results showed that 8.3% polyvinyl alcohol, 74.7% polyvinylpyrrolidone K30, 12% oleic acid-azone, and 5% polyacrylic acid resin II provided an optimized TDDS product for effective administration of LP and VPH. Furthermore, in vitro and in vivo release tests showed that the system continuously released LP and VPH for 24 h. The pharmacokinetic results indicated that although the maximum concentration was lower, both the area under the curve from 0–time and the mean residence time of the prepared patch were significantly higher than those of the oral preparations. Furthermore, the prepared LP-VPH transdermal patch showed good stability and no skin irritation. The developed LP-VPH TDDS showed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it is an ideal formulation. Full article

Low fluvial terraces present azonal spatialization, encompassing several geomorphological compartments and climate zones in Brazil. Their genesis is directly related to river dynamics. When influenced by allogenic forces, such as Holocene climate pulses, it results in channel incision and posterior abandonment of the floodplain. Relatively plain landforms at different altimetric levels identified between the current floodplain and hillslope (low river terraces) are a result of these processes. Previous works using Optically Stimulated Luminescence (OSL) in low terraces of several rivers in Brazil have indicated morpho-chronologic similarities between depositional events, raising the hypothesis of feedbacks and fluvial adjustments relatively simultaneous to Holocene climate events. Considering these dynamics, this study employed OSL to obtain absolute dating information for 114 samples taken from distinct levels of the low river terraces of 30 rivers in Brazil, integrating the database of the IG-UNICAMP laboratory of Geomorphology and Environmental Analysis. Based on the data and statistical analysis (cluster and correlation analysis), this study aimed to identify relationships between different variables which might have controlled spatial homogenous and heterogeneous feedbacks during distinct paleoenvironmental contexts. The proposed methodology tested a fundamental hypothesis of the regional climatic geomorphology, and the results obtained may contribute to future discussions on the relationship between low river terraces and anthropic occupation. Full article

This study includes a general description of the Earth’s karst types based on literary data and field observations. An improved classification of karst types distinguishes the main group, group, and subgroup; and, a division of karst types involves a main karst type, karst type, subtype, variety, and non-individual karst type. The relation between karst type and karst area is described. The role of various characteristics of karsts in the development of primary, secondary, and tertiary karst types is analyzed. Their structure is studied, which includes a geomorphic agent, process, feature, feature assemblage, karst system and the characteristics of the bearing karst area. Dominant, tributary, and accessory features are distinguished. The conditions of the stability and the development of types are studied, transformation ways are classified, and the effect of climate on types is described. Full article

Transdermal drug delivery is an attractive non-invasive method offering numerous advantages over the conventional routes of administration. The main obstacle to drug transport is, however, the powerful skin barrier that needs to be modulated, for example, by transdermal permeation enhancers. Unfortunately, there are still only a few enhancers showing optimum properties including low toxicity and reversibility of enhancing effects. For this reason, we investigated a series of new N-alkylmorpholines with various side chains as potential enhancers in an in vitro permeation study, using three model permeants (theophylline, indomethacin, diclofenac). Moreover, electrical impedance, transepidermal water loss, cellular toxicity and infrared spectroscopy measurements were applied to assess the effect of enhancers on skin integrity, reversibility, toxicity and enhancers’ mode of action, respectively. Our results showed a bell-shaped relationship between the enhancing activity and the hydrocarbon chain length of the N-alkylmorpholines, with the most efficient derivatives having 10–14 carbons for both transdermal and dermal delivery. These structures were even more potent than the unsaturated oleyl derivative. The best results were obtained for indomethacin, where particularly the C10-14 derivatives showed significantly stronger effects than the traditional enhancer Azone. Further experiments revealed reversibility in the enhancing effect, acceptable toxicity and a mode of action based predominantly on interactions with stratum corneum lipids. Full article