Search Results (8,389)

Background/Objectives: Niaprazine is widely used for the management of sleep disorders in pediatric and geriatric patients; however, no commercially available oral liquid formulation is currently available in Italy, making extemporaneous compounding necessary. In routine practice, the beyond-use date (BUD) is often limited to 30 days, potentially affecting therapeutic continuity. This study aimed to evaluate the chemical, physical, and microbiological stability of a compounded niaprazine syrup to support evidence-based BUD and to assess the suitability of selected ready-to-use compounding vehicles for preparing alternative niaprazine oral liquid formulations. Methods: A niaprazine syrup (3 mg·mL⁻¹) was prepared in a sucrose-based vehicle acidified with tartaric acid and preserved with potassium sorbate. Chemical stability of niaprazine was evaluated by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD), whose specificity was confirmed by forced degradation studies. Stability was monitored for up to 9 months at 4–8, 25, and 40 °C and confirmed after 12 months by HPLC-DAD and mass spectrometry (MS). Physical stability of the formulation was monitored by pH and visual inspection up to 12 months. Microbiological quality was assessed for 2 months at 4–8 and 25 °C according to the European Pharmacopoeia. In parallel, four selected ready-to-use compounding vehicles were evaluated for their suitability to prepare stable niaprazine oral liquid formulations. Results: Niaprazine concentrations in the syrup remained within pharmacopeial acceptance limits (±10%) at all temperatures, although a decrease was observed under accelerated conditions (40 °C). pH remained stable (≤0.5-unit variation) and the formulation stayed clear and homogeneous throughout the study, with only minor visual changes after prolonged storage at 40 °C. Statistically significant differences (p < 0.05) were observed in both the HPLC-DAD and HPLC-MS datasets. Microbiological testing confirmed compliance up to 2 months at 4–8 and 25 °C (TAMC ≤ 10³ CFU/mL; TYMC ≤ 10² CFU/mL; Escherichia coli absent). Comparable chemical and physical stability was observed for three of the four formulations prepared with the ready-to-use vehicles over at least two months. Conclusions: The compounded niaprazine syrup demonstrated chemical, physical, and microbiological stability under refrigerated and room-temperature storage, supporting evidence-based beyond-use dating of up to two months under the tested conditions. Ready-to-use vehicles may represent a practical complementary approach, offering standardized alternatives for the preparation of niaprazine oral liquid formulations. Full article

Laterite is an acidic tropical soil enriched in iron and manganese. It is common at tropical death scenes, yet its effect on necrophagous insect development is unstudied. We raised the forensically important blow fly Chrysomya megacephala (Fabricius, 1794) on three Hainan laterites, a yellow earth control, and a no-soil substrate. We combined larval phenotyping, inductively coupled plasma mass spectrometry (ICP-MS), and untargeted ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) metabolomics of whole larvae sampled on Days 1–3 post-burrowing. Laterites were strongly acidic (pH 4.17–4.32 vs. 7.45) and Fe/Mn-enriched. Whole-larval Fe (~10.2-fold) and Mn (~4.1-fold; whole larvae including gut contents, as no gut evacuation was performed) were consistently elevated across the three laterites, without biomagnification (bioaccumulation factors < 1). Laterite-group larvae were significantly heavier from 106 h and shorter from 130 h of age. They entered the cryptocephalic stage at 130 vs. 154 h and pupariated 24 h earlier in shallower soil (3–5 vs. 8–10 cm). In the primary merged metabolome analysis (n = 5–6 per group; 2975 metabolites), no metabolite survived the Benjamini–Hochberg correction in any laterite comparison, whereas three did in the no-soil comparison. The level-1 candidate metabolites are therefore hypothesis-generating. Laterite thus alters larval development and whole-body metal content. This implies a potential ~1-day bias in postmortem interval estimation under controlled conditions. Full article

This study established an activity-oriented analysis method based on offline two-dimensional liquid chromatography–electrochemical detection (2D-LC-ECD) combined with ultra-high-performance liquid chromatography–Orbitrap-MS/MS (UHPLC-Orbitrap-MS/MS), which was used to comprehensively characterize the antioxidant components of Polygonum multiflorum Thunb. leaves (PML) and screen for differential compounds in samples from different origins. Antioxidant components were screened using 2D-LC-ECD combined with in vitro radical scavenging experiments; structure identification was conducted via UHPLC-Orbitrap-MS/MS, and chemometric analysis alongside quantitative determination of 19 major components was carried out across 31 batches of samples. A total of 43 potential antioxidant compounds were identified from PML, including 11 phenolic acids, 29 flavonoids, 2 stilbene glycosides, and 1 amino acid; phenolic acids and their derivatives, along with flavonoids, were identified as major contributors to antioxidant activity. Hierarchical clustering analysis and principal component analysis both grouped samples into four categories by origin; the orthogonal partial least squares discriminant analysis model (R²X = 0.933, R²Y = 0.941, Q² = 0.846) screened 10 key markers (VIP > 1). The quantitative results showed that polygonacetophenoside had the highest content in PML. In summary, the 2D-LC-ECD coupled with LC-Orbitrap-MS/MS strategy confirmed that phenolic acids and flavonoids are the core material basis for PML’s antioxidant capacity, providing scientific evidence for the industrial development of PML as a natural antioxidant. Full article

Abelmoschus manihot (L.) flowers are widely used in traditional Chinese medicine, whereas the roots are often discarded as agricultural waste. The compact cellular and tissue architecture of the roots hinders the release of intracellular metabolites, thus impeding their reutilization. Here, enzyme-assisted ultrasonic extraction was developed to obtain a polysaccharide-rich crude extract from A. manihot roots. Orthogonal optimization identified pH 4.5, a temperature of 60 °C and a cellulase dosage of 6% (w/w) as the optimal extraction conditions, giving an extraction yield of 21.59%. The phenol–sulfuric acid assay indicated a total carbohydrate content of 75.09% (glucose equivalents). Structural analysis by Fourier transform infrared (FT−IR) confirmed the presence of characteristic polysaccharide functional groups, while monosaccharide composition analysis via high-performance liquid chromatography (HPLC) revealed the major components of glucose, glucuronic acid, rhamnose, galacturonic acid, etc. Inspired by the traditional use of A. manihot extract in papermaking, its preliminary hair care-related properties were further evaluated. At a concentration of 30 mg/mL, the extract solution inhibited Malassezia furfur growth by 84%, reduced wet and dry combing work by 16.93% and 30.86%, and increased tensile strength and tensile fracture energy by 13.04% and 14.84%, respectively. Scanning electron microscope (SEM) images suggested smoother hair fiber surfaces after treatment. These results highlight the extract’s great potential for hair care cosmetic products. Full article

Bamboo leaves contain structurally diverse flavonoid glycosides; whereas, compound-level information for Bambusa textilis remains limited. In this study, a flavonoid-enriched 40% ethanol fraction prepared from B. textilis leaves by petroleum-ether partitioning and AB-8 resin adsorption was analyzed by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS/MS) in negative-ion mode. Retention times and MS/MS spectra were compared with seven in-house reference standards, while the remaining constituents were annotated from accurate-mass measurements, diagnostic product ions, fragmentation behavior, and data from the literature. According to Metabolomics Standards Initiative criteria, seven compounds were assigned at Level 1 and twenty-four were reported as Level 3 annotations because their exact positional structures were not confirmed by additional standards or NMR. Thirty-one flavonoid-related constituents were annotated in the analyzed fraction, encompassing six glycoside classes; most annotations, by count, were apigenin- or luteolin-derived. These annotations add compound-level information for the analyzed B. textilis fraction and allow qualitative comparison with other bamboo flavonoid profiles. Because the sample was selectively enriched, the results do not describe the complete leaf metabolome or compound concentrations. Additional standards or NMR analysis are needed to confirm the glycosylation positions of tentatively annotated compounds. Full article

Background/Objectives: Heracleum millefolium Diels (HMD) is a traditional Tibetan medicinal herb that has been reported to possess analgesic, anti-edematous, and anti-inflammatory activities. However, its chemical composition and anti-inflammatory mechanisms remain unclear. Methods: In this study, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS), combined with database searching and “seed”-based molecular networking, was used to systematically characterize the chemical constituents of HMD. Furthermore, an integrated strategy combining network pharmacology, molecular docking, and cellular validation was applied to explore potential anti-inflammatory mechanisms associated with HMD. Results: A total of 472 compounds were identified or tentatively identified from HMD. Network pharmacology analysis predicted five key targets, namely TNF, IL-6, IL-1β, GAPDH, and AKT1, together with four potential bioactive constituents, including velutin, artemitin, kaempferol, and naringenin. Pathway enrichment analysis indicated that the potential anti-inflammatory effects of HMD were mainly associated with lipid and atherosclerosis and the AGE-RAGE signaling pathway. Molecular docking suggested potential favorable interactions between the selected constituents and key targets. Moreover, cellular experiments demonstrated that the four compounds significantly inhibited inflammatory responses in LPS-stimulated RAW264.7 macrophages. Conclusions: This study systematically characterized the chemical profile of HMD and preliminarily explored its potential anti-inflammatory mechanisms, providing a scientific basis for further investigation of its bioactive constituents and pharmacological properties. Full article

The photocatalytic degradation of Acid Orange 7 (AO7) in aqueous solution in the presence of exfoliated C₃N₄ (n-C₃N₄) as a photocatalyst was investigated under simulated solar light irradiation. The n-C₃N₄ photocatalyst was synthesized by polymerization of urea as a precursor and characterized by UV/Vis and FTIR spectroscopy, and transmission electron microscopy. Degradation products were identified by high-performance liquid chromatography with high-resolution mass spectrometry (LC–HRMS). It was found that AO7 undergoes a series of oxidation steps mediated by radicals generated during light absorption by n-C₃N₄, as well as through a photosensitization process initiated by light absorption by AO7. This results in decolorization and the formation of aromatic and aliphatic intermediates, which undergo further oxidation to simpler compounds. Full article

Background/Objectives: Delonix regia seeds contain phytochemicals with therapeutic potential, but their activity against Helicobacter pylori and biomedical properties remain incompletely characterized. This study aimed to characterize the phenolic and amino acid composition of D. regia seed extract (DRSE) and evaluate its anticancer, wound-healing, anti-inflammatory, anticoagulant, antibacterial, antibiofilm and urease-targeted docking activities. Methods: DRSE was analyzed by high-performance liquid chromatography (HPLC) and amino acid analysis. Biological effects were assessed using MTT cytotoxicity, scratch wound-healing, bovine serum albumin (BSA) denaturation, prothrombin time (PT) and partial thromboplastin time (PTT), antibacterial and crystal violet antibiofilm assays. Gallic acid and vanillin were docked against H. pylori urease (PDB ID: 1E9Y). Results: Gallic acid was the predominant phenolic compound (1417.90 µg/g), while aspartic and glutamic acids dominated the amino acid fraction. DRSE showed preferential cytotoxicity toward A431 carcinoma cells (IC₅₀ = 108.97 ± 0.68 µg/mL) compared with HFB4 fibroblasts (IC₅₀ = 318.56 ± 2.06 µg/mL), yielding a selectivity index of 2.92. Scratch closure was comparable to the control (81.71% versus 80.85%), although the migration rate increased to 16.12 µm. DRSE inhibited protein denaturation by 91.20% (IC₅₀ = 6.39 ± 0.19 µg/mL) and prolonged PT and PTT to 27.37 and 90.50 s, respectively. It inhibited H. pylori with minimum inhibitory and bactericidal concentrations of 31.25 µg/mL and suppressed biofilm formation by 95.39%. Gallic acid and vanillin showed comparable urease docking scores of −4.72 and −4.71 kcal/mol. Conclusions: DRSE showed selective anticancer, anti-H. pylori, antibiofilm, anti-inflammatory, anticoagulant, and moderate pro-migratory activities. Mechanistic, safety and in vivo studies are warranted. Full article

Background/Objectives: This study engineered and evaluated a targeted, folate-functionalized chitosan nanoparticle (CS-FA NP) delivery system to enhance the therapeutic efficacy of standard quercetin and Coriandrum sativum seed extract against breast cancer. Methods: Phytochemical profiling confirmed a 14% crude yield for the methanolic extract, with gas chromatography–mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) identifying quercetin as the principal bioactive agent. The synthesized CS-FA NPs exhibited a core size of 7–20 nm, an average hydrodynamic diameter of 150–160 nm, a stable zeta potential of −55 mV, and high encapsulation efficiencies (87.2% for quercetin and 80.5% for coriander). Kinetic assessments confirmed a biphasic, diffusion-controlled release matching Higuchi matrix kinetics. Anticancer activity was evaluated in vitro using MTT cytotoxicity, Annexin V-FITC/PI apoptosis analysis, RT-qPCR, and ex vivo rat aortic ring assays, followed by validation in a syngeneic 4T1 mammary tumor mouse model. Results: In vitro, folate-receptor-targeted quercetin nanoparticles (T4) demonstrated superior, selective cytotoxicity, particularly against triple-negative MDA-MB-231 cells, while sparing normal fibroblasts. Annexin V-FITC/PI apoptosis profiling and ex vivo aortic ring assays revealed profound, cell-line-dependent programmed cell death and up to 90% inhibition of microvessel sprout outgrowth. Mechanistically, RT-qPCR verified that nano-formulations induced complete transcriptional silencing of NANOG, MMP-1, VEGFA, TSPAN8, TWIST, EMMPRIN, and CDK1, alongside marked upregulation of P27^KIP1 and P21^CIP1. In vivo, these nano-formulations successfully improved tumor-associated pathological features, reduced aggressive tumor spindle-cell proliferation, and suppressed elevated serum CA15-3 and arginase biomarkers. Conclusions: Folate-functionalized chitosan nano-formulations significantly enhanced the anticancer efficacy of quercetin and Coriandrum sativum seed extract through improved targeted delivery, potent antiproliferative, anti-angiogenic, and pro-apoptotic activities, together with favorable modulation of multiple molecular pathways associated with breast cancer progression. These findings support their potential as promising targeted nanotherapeutic strategies for breast cancer treatment. Full article

Retinol, a bioactive small molecule of the vitamin A family, contributes epidermal and dermal tissue repair through retinoic acid receptor γ (RARγ)/retinoid X receptor (RXR) receptor-mediated transcriptional regulation of keratinocyte differentiation, extracellular matrix (ECM) remodeling, and barrier restoration. However, the relationship between applied concentration, tissue-level regenerative outcomes, and tolerability remains incompletely characterized. This prospective, randomized, single-blind study compared biophysical effects and tolerance of two retinol concentrations in EU-compliant facial creams, high-performance liquid chromatography (HPLC)-verified as 0.104% and 0.247% (w/w). Thirty-eight women aged 40–61 years (Fitzpatrick phototypes II–III) participated across three independent sub-studies: 28 were randomized to either concentration for 12 weeks; 5 underwent split-face ultrasound imaging (0.247% versus retinol-free control) for 8 weeks; and 5 participated in a tape stripping sub-study quantifying stratum corneum interleukin-1 alpha (IL-1α) and interleukin-1 receptor antagonist (IL-1ra) by ELISA before and after 6 weeks of 0.247% retinol treatment. Main cohort assessments included transepidermal water loss (TEWL), hydration, melanin, erythema, pH, sebum, biomechanical parameters, and wrinkle grading. Both concentrations significantly improved barrier parameters—hydration, TEWL, brightness, pH, and sebum—with no inter-group differences. In the ultrasound sub-group, 0.247% retinol increased epidermal thickness (+12.4 μm), epidermal density (+3.84%), and dermal density (+1.81%) versus control, consistent with ECM reorganization and epidermal stratification. Biomechanical parameters showed no significant changes, consistent with retinol’s remodeling timeline. Consumer assessment indicated comparable efficacy; 0.247% demonstrated superior smoothing but higher erythema incidence. In the tape stripping sub-study, IL-1α decreased in all participants (median: 25.1 → 13.2 picograms per tape [pg/Tape]; 5/5 concordant), while IL-1ra increased in 4/5 participants (median: 352.8 → 1403.1 picograms per three sequential tapes [pg/3sT]), indicating a directionally consistent shift in the IL-1α/IL-1ra balance; these results are exploratory and require replication in larger cohorts. These findings collectively support clinically meaningful barrier restoration and structural remodeling within current EU safety limits (Commission Regulation EU 2024/996), with 0.104% offering a favorable efficacy-to-tolerability profile for initial therapy. Full article

Background: Ceftobiprole medocaril (Zevtera^®) is an injectable broad-spectrum antibiotic. Objective: We aim to show that ceftobiprole initiated in hospital may be continued at home through Outpatient Parenteral Antibiotic Therapy (OPAT). Methods: Solutions of ceftobiprole at 2.0 and 2.8 mg/mL were prepared in PVC bags from 500 mg vials and stored at room temperature (RT) or 4 °C. Each sample was analyzed in triplicate samples using high-performance liquid chromatography (HPLC) at multiple time points over a 120 h period. Additionally, 2.5 mg/mL ceftobiprole solutions were prepared in Intermate^® infusion devices (n = 3 preparations) and stored at 4 °C. Samples were collected on multiple days from Day 0 to Day 9, both immediately post-refrigeration and after 8 h at RT and analyzed in triplicate. Results: PVC bag solutions retained ≥90% of their initial concentrations. At RT, residual concentration was 90.9% (2.0 mg/mL) and 92.0% (2.8 mg/mL) after 24 h. At 4 °C, the 2.0 mg/mL formulation retained 90.8% after 120 h, and the 2.8 mg/mL formulation retained 90.2% after 96 h. Intermate^® devices stored nine days at 4 °C and exposed to RT for 8 h retained ≥90% of the initial concentration of ceftobiprole (2.5 mg/mL; 93.3% before RT exposure; 91.1% after). Conclusions: Ceftobiprole medocaril exhibits sufficient physicochemical stability for OPAT use in PVC bags and Intermate^® infusion device under tested conditions. Full article

To explore the high-value utilization of liquid recovery products from waste wind turbine blades in road binders, a liquid-rich fraction obtained from subcritical acetic acid degradation and subsequent vacuum distillation of waste wind turbine blade epoxy composites was introduced into styrene–butadiene–styrene (SBS)-modified asphalt to prepare composite-modified asphalt. Conventional property tests, dynamic shear rheological tests, bending beam rheological tests, steady shear tests, master curve analysis, Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC) were conducted to systematically evaluate the influence of the liquid-rich fraction on the properties and structural characteristics of the composite-modified asphalt. The results showed that, with increasing liquid-rich fraction content, the softening point increased, while penetration and ductility decreased, and the rotational viscosity at 135 °C increased, indicating enhanced overall stiffness and high-temperature flow resistance. High-temperature rheological results showed that the liquid-rich fraction increased the storage modulus, loss modulus, and rutting factor, while decreasing the phase angle improved the high-temperature deformation resistance of the composite-modified asphalt. Low-temperature rheological results indicated that the creep stiffness S increased, the m-value decreased, and the S/m ratio increased, suggesting weakened stress relaxation capacity and reduced cracking resistance at low temperature. Fatigue factor and steady shear results revealed that the liquid-rich fraction enhanced structural stability and flow resistance but also increased fatigue damage sensitivity at intermediate temperature. Master curves, Black diagram, and Cole–Cole plots further demonstrated that the liquid-rich fraction increased the modulus level over a wide frequency domain and strengthened the structural stability of the asphalt system. FTIR and GPC results indicated that the introduction of the liquid-rich fraction increased the relative contents of aromatic structures and polar oxygen-containing groups and promoted molecular association and increased the apparent molecular weight level of the system. Overall, the liquid-rich fraction acted as a structure-enhancing modifier in SBS-modified asphalt, improving its high-temperature performance while causing a certain trade-off in low-temperature and fatigue properties. Therefore, the dosage should be selected by balancing high-temperature stability, low-temperature cracking resistance, and fatigue durability, and the practical sustainability of this recycling route still requires dedicated economic and environmental evaluation. Full article

Solanum elaeagnifolium has been utilized for its analgesic, anti-inflammatory, and antioxidant properties to treat a range of conditions, including pain and inflammation. It possesses antibacterial, insecticidal, and molluscicidal properties as well. To investigate the pharmacological potential of the S. elaeagnifolium extract, in vitro, in vivo, and in silico studies were used. Albumin denaturation, heat-induced anti-haemolytic action, and lipooxygenase inhibition were the three techniques used to test anti-inflammatory effectiveness. The phenolic chemicals utilized were identified through the use of high-performance liquid chromatography (HPLC). The effectiveness of the extract in lowering problems connected to diabetes was further evaluated by evaluating fructosamines, carbonyl groups, and β-amyloid formations in albumin glycation. Regarding in vivo studies, the Writhing test and the tail flick test were the two techniques used to evaluate analgesic activity. For docking analysis, we used the following identifiers: cyclooxygenase (PDB ID: 6COX), lipooxygenase (PDB ID: 3V99) and VC1 domain of the receptor for advanced glycation products (PDB ID: 7LMW). The most prevalent phenolic chemicals, according to HPLC analysis, were 3,4-dihydroxybenzoic acid (4.78%), caffeic acid (1.28%), gallic acid (8.18%), ursolic acid (2.6%), syringic acid (1.78%), quercetin (24.09%), catechin (6.67%), and p-coumaric acid (20.49%). Significant suppression of albumin glycation and fructosamine production was demonstrated by the extract, indicating that it may help lessen difficulties associated with diabetes. Furthermore, the extract demonstrated a strong anti-inflammatory impact, with an IC₅₀ of 146 ± 1.17 μg/mL for lipooxygenase inhibition, 87.64 ± 5.35 μg/mL for anti-haemolytic action, and 86.94 ± 1.63 μg/mL for albumin denaturation inhibition. A similar analgesic effect to those of analgesic medications was also demonstrated by SEFE extract. Reinforcing the relevance of the observed effects, the in silico study of the tested activities validated these findings. These findings indicate significant pharmacological promise in the management of diabetes consequences, including inflammation and protein glycation, as well as an analgesic. Full article

Endocrine-disrupting compounds (EDCs) are frequently detected in wastewater and aquatic environments because of their incomplete removal in conventional wastewater treatment plants. Evaluating alternative treatment technologies, including microalgae-based systems, requires analytical methods suitable for low-volume samples. In this work, a solid-phase extraction (SPE) procedure coupled with high-performance liquid chromatography with diode array detection (HPLC-DAD) was developed for the simultaneous determination of methylparaben (MeP), propylparaben (PrP), butylparaben (BuP), benzophenone (BP), bisphenol A (BPA) and estrone (E). The method combines relatively low sample volume and limited eluent consumption with the analysis of six chemically diverse EDCs in biomass-containing samples using accessible HPLC-DAD instrumentation. Sorbent mass, sample volume, elution volume, and pH were evaluated experimentally, with Random Forest used for exploratory multivariable interpretation. Selected conditions were a 500 mg cartridge, 30 mL of sample volume at pH 7 and 2 mL methanol elution volume. The method showed satisfactory linearity (R² ≥ 0.98), limits of quantification between 1.67 and 6.67 ppb, and stable recoveries across the evaluated concentration range. Applicability was demonstrated in a Scenedesmus sp.-based system. AGREEprep assessment yielded a score of 0.34. The developed SPE method provides a low-volume approach for monitoring EDCs in microalgae-based wastewater treatment systems. Full article

Skin ageing is associated with oxidative stress, mitochondrial dysfunction, extracellular matrix alterations, and impaired barrier function, supporting interest in antioxidant cosmeceuticals for mature skin. This study investigated the antioxidant activity of melatonin and N-acetylcysteine, the in vitro permeation of melatonin from different cream formulations, and their preliminary clinical performance in women aged 55–65 years. Antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)/Trolox equivalent antioxidant capacity (ABTS/TEAC) assays. Melatonin permeation across Strat-M^® membranes was evaluated using Franz diffusion cells and quantified by a validated high-performance liquid chromatography method coupled with a photodiode-array detection (HPLC-PDA) method. Clinical changes were assessed over 28 days using the Glogau wrinkle scale and a lower facial ptosis scale. N-acetylcysteine exhibited greater antioxidant activity than melatonin in the DPPH assay, with half-maximal inhibitory concentration (IC₅₀) values of 5.96 ± 1.02 and 530.11 ± 48.63 µg/mL, respectively. Melatonin permeation varied according to formulation composition, with cumulative amounts after 24 h ranging from 81.27 ± 17.47 to 1043.48 ± 33.43 µg/cm². Reductions in periocular wrinkle and lower facial ptosis scores were observed after 28 days. These preliminary findings support further investigation of melatonin–N-acetylcysteine creams for mature skin. However, the present membrane model did not assess cutaneous retention, and the clinical observations require confirmation in larger, controlled studies. Full article