Search Results (63)

Background: Egg allergy is one of the most common food allergies in early childhood and is traditionally managed through strict avoidance diets, which may negatively affect nutrition and quality of life. Early oral immunotherapy (OIT) may represent an alternative therapeutic strategy; however, controlled studies in children younger than two years remain limited. Methods: We conducted a prospective observational study using historical controls. Thirty-one children younger than two years with IgE-mediated egg allergy underwent OIT using pasteurized liquid egg white (maximum dose: 30 mL; 3300 mg protein). Twelve children managed with an avoidance diet served as the historical control group. Outcomes included desensitization rates, adverse reactions, and longitudinal changes in skin prick test (SPT) wheal diameters, serum-specific IgE (sIgE), specific IgG4 (sIgG4), and sIgE/total IgE ratios. Results: At six months, 29/31 children (93.5%) in the OIT group did not experience allergic reactions after ingestion of any egg preparation, compared with none in the historical control group (p < 0.001). In the control group, 7/12 children (58.3%) continued to react to less-cooked egg preparations, whereas 5/12 (41.7%) remained reactive to all forms of eggs. During the induction phase, 24/31 OIT-treated children (77.4%) experienced mild adverse reactions, predominantly isolated cutaneous or gastrointestinal symptoms, and no patient required intramuscular adrenaline administration. In contrast, allergic reactions occurred in 11/12 controls, including anaphylaxis in 6/12 (50.0%) patients (p = 0.0301). The OIT group demonstrated significant reductions in SPT wheal diameters, sIgE levels, and sIgE/total IgE ratios (all p < 0.001), accompanied by increased sIgG4 levels. Conclusions: Early OIT with pasteurized egg white in children younger than two years with IgE-mediated egg allergy was associated with high desensitization rates, favorable short-term safety outcomes, and significant immunological changes. These findings support the potential role of early active intervention as an alternative to exclusive avoidance strategies in infants with egg allergy. Full article

Microelectromechanical systems are being increasingly deployed in nuclear industry robotics, where their great sensitivity and mechanically stable silicon structures enable reliable sensing in radiation-exposed environments. An ultra-thin silicon strain gauge without an oxide substrate layer designed for robotic electronic skin is evaluated under Co-60 γ irradiation, representative of nuclear decommissioning conditions. The sensor performance is evaluated based on electrical measurements conducted before and after irradiation, focusing on cumulative radiation-induced effects. The results show that silicon strain gauge signal maintains a high linearity (R² > 0.99) under strain. Across an accumulated dose range up to approximately 15 Gy, only minor variations are observed, including a resistance increase within 1.3% and a reduction in gauge factor within 5% for most specimens. The radiation-induced resistance increases and sensitivity degradation results in a maximum strain estimation error of approximately 22.5 με (≈3.5%) within the tested operating range below 700 με. Full article

Background/Objectives: In the broad and current context of antimicrobial resistance, antibiotic management and therapeutic surveillance are essential in hospitals. The present study (five-year retrospective, 2020–2024) aimed to analyze antibiotic consumption in relation to pathogens identified in a multidisciplinary hospital. Results: In terms of antibiotic consumption (overall 2020–2024), although initially Watch antibiotics were predominantly used, a decrease was observed in favor of Access class antibiotics (sharply increase from 2022 to 2023 and maximum in 2024). For Reserve antibiotics, only slight annual fluctuations were observed, but there was an important reduction in colistin consumption. The most used were cephalosporins (cefazolin, cefuroxime and ceftriaxone), carbapenems (meropenem and ertapenem), vancomycin and linezolid. Regarding pathogens, the most notable were: Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterococcus spp., Pseudomonas aeruginosa. Among the ESKAPE bacteria, Acinetobacter baumannii was the least frequent in our samples. ESKAPE bacteria predominantly colonized specimens from the respiratory tract, digestive tract, skin and soft tissue. Resistant strains were observed, mainly Methicillin-resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) Klebsiella spp., but no alarming increases in number were recorded in the analyzed period. Methods: The analysis was carried out using tools recommended by the World Health Organisation (Access Watch Reserve antibiotics classification (AWaRe); Bacterial Priority Pathogen List (BBPL); Defined Daily Dose (DDD)), Average Annual Percent Change (AAPC) calculation and ESKAPE classification (bacteria group: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.). Conclusions: Relatively stable trends in bacterial isolates and resistant strains over five years (2020–2024) are consistent with effective antimicrobial stewardship practices. Full article

Growing interest in natural therapies has increased the demand for essential oils; however, the complex interactions within their mixtures that dictate their final efficacy remain poorly understood. This study aimed to optimize a blend of ginger, cinnamon, tea tree, and geranium essential oils to develop an active ingredient, with synergistic multifunctional bioactivities, that was relevant to cutaneous healing. Initially, the composition and cytotoxicity for individual oils were determined; subsequently, a D-optimal mixture design was employed to evaluate three biological responses related to skin recovery: ultraviolet B radiation absorption, red blood cell lysis inhibition, and catalase enzyme activity. GC-FID analysis revealed the following major components (% w/w): cinnamon (cinnamaldehyde, 77.56%), ginger (α-zingiberene, 33.77%), geranium (citronellol, 33.6%), and tea tree (terpinen-4-ol, 38.38%). Dose–response data from essential oils tested against Detroit ATCC 551 skin fibroblasts revealed a clear cytotoxic hierarchy (IC₅₀ µg/mL): cinnamon (21.03) > ginger (25.3) > tea tree (41.67) > geranium (92.51). Cinnamaldehyde content was the primary contributor to photoprotective capacity, with a maximum sun protection factor (SPF) of 4.5. Inhibition against erythrocyte membrane lysis was not attributable to a single component; maximum protection (98.4%) was achieved through synergy between oxygenated monoterpenoids (geranium and tea tree), sesquiterpenes (ginger), and aromatic aldehydes (cinnamon). Highest catalase activity (160.86 kU/g Hb) was reached in mixtures with high cinnamaldehyde and eugenol contents, whereas an antagonistic effect was observed between tea tree and geranium oils. Finally, an optimal formulation (desirability = 0.927) was identified (% w/w): 31.7% ginger, 39.1% cinnamon, 14.5% tea tree, and 14.7% geranium. Experimental validation confirmed no significant difference compared with developed predictive models. This optimized mixture constitutes a bioactive natural component with potential for use in products aimed at promoting skin health, warranting further investigation into direct models of skin healing. Full article

Background/Objectives: Nanoemulsions (NEs) are a promising platform for transdermal drug delivery (TDD); however, how the polarity of the active pharmaceutical ingredient (API) influences NE structure–performance relationships remains insufficiently understood. This study aimed to systematically compare the transdermal delivery behavior of a hydrophilic API, salbutamol hemisulphate (log P ≈ 0.1), and a lipophilic API, ibuprofen (log P ≈ 3.3), incorporated into compositionally matched nanoemulsion systems. Methods: Kolliphor EL–based NEs were prepared using identical excipients, with systematic variation of oil, surfactant, and water ratios. Thirty-six formulations were produced for each API. Physical stability, droplet size, and viscosity were characterized, and in vitro skin permeation studies were conducted using excised mouse skin. Flux and cumulative permeation were quantified, and statistical analyses were performed to identify key compositional drivers of permeation. Results: Ibuprofen-containing NEs exhibited superior physical stability compared to salbutamol formulations, likely due to interfacial interactions that imparted surfactant-like behavior. Both APIs formed nanoscale droplets, with salbutamol formulations ranging from 16 to 507 nm and ibuprofen formulations spanning 12–563 nm, more frequently yielding sub-100 nm droplets. Viscosity values covered broad ranges (3–9532 mPa·s for salbutamol; 13.4–9759 mPa·s for ibuprofen), with salbutamol generating an extended high-viscosity domain at 50% (w/w) surfactant and ibuprofen showing a narrower viscosity maximum at 30–40% surfactant. Salbutamol NEs achieved high fluxes (up to 374 µg/cm²·h) and cumulative permeation of approximately 80% of the applied dose, whereas ibuprofen formulations showed markedly lower fluxes (maximum 32 µg/cm²·h) and cumulative permeation below 6%. High surfactant levels suppressed permeation for both APIs, but the dominant positive drivers differed: balanced oil–water ratios for salbutamol and hydration-dependent diffusional resistance for ibuprofen. Conclusions: These findings demonstrate that API polarity and interfacial portioning behavior decisively govern NE performance, providing a framework for rational tailoring of oil–surfactant–water ratios to maximize transdermal delivery efficiency. Full article

Background/Objectives: Dalbavancin is approved for pediatric acute bacterial skin and skin structure infections (ABSSSIs), yet real-world practice frequently necessitates off-label use for deep-seated infections requiring prolonged suppression. While adult data support therapeutic drug monitoring (TDM)-guided maintenance, the pediatric evidence for repeated-dose pharmacokinetics (PK) is limited. We evaluated the efficacy, safety, multi-dose PK, and pharmacoeconomic impact of dalbavancin in a complex pediatric cohort. Methods: A retrospective study (2023–2025) of enrolled patients < 18 years treated with dalbavancin. A subgroup receiving ≥3 doses underwent PK analysis to assess concentration decay against conservative efficacy targets (4 and 8 mg/L). A pharmacoeconomic analysis compared resource utilization against the standard of care. Results: Sixteen patients (median age 12) were included, primarily treated for Staphylococcus aureus (S. aureus) osteoarticular infections (75%), and frequently device-associated (66.7%). Clinical success was 93.8% (15/16) with no adverse events. A PK analysis (n = 9; 78 samples) ruled out dangerous accumulation but revealed a significant concentration drop at week 4 (mean 6.06 mg/L; p = 0.005). Logistic regression identified the time since the previous dose as the sole predictor of sub-therapeutic levels, with >50% of the patients dropping below 8 mg/L by the fourth week. An analysis showed median net savings of EUR 3215.84 per patient (p = 0.004). Conclusions: Dalbavancin is effective and cost-saving for complex pediatric infections. However, due to distinct pediatric PK, dosing regimens extrapolated from adults may result in sub-therapeutic concentrations by week 4. We recommend TDM around week 3 to tailor dosing or limiting maintenance intervals to a maximum of 4 weeks. Full article

Background: Lidocaine, classified as an amide-type agent, and tetracaine, designated as an ester-type agent, are frequently co-formulated for dermatologic procedures. Despite the extensive literature on the pharmacokinetics (PK) of these substances, there is a paucity of head-to-head comparisons of intravenous (IV) and topical administration in the same preclinical model. Absolute bioavailability (F%) is imperative for optimizing formulation design and safety. Methods: A single-dose, single-sequence, three-period pilot study was performed in male Göttingen mini-pigs. The first period of the study involved the intravenous bolus administration of lidocaine HCl and tetracaine HCl, with a dosage of 1 mg/kg for each agent. In Period 2, the topical application of Pliaglis (a combination of 7% lidocaine and 7% tetracaine, with a concentration of 10 g/100 cm² and a duration of 60 min) was utilized. In Period 3, the pharmacokinetic profile of Z4T4L4 (a formulation comprising 4% lidocaine HCl and 4% tetracaine HCl) was assessed under the same experimental conditions. Blood samples were collected up to 24 h after the administration of the drug; skin biopsies were obtained 90 min after the application of the test substance. Plasma and skin concentrations were measured by means of validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). PK parameters were derived using a noncompartmental analysis approach, while F% was calculated through AUC comparison with IV dosing. Results: Subsequent to intravenous administration, the mean elimination half-lives of lidocaine and tetracaine were determined to be 1.62 h and 1.85 h, respectively. Pliaglis demonstrated higher skin concentrations of lidocaine (358 μg/g) and tetracaine (465 μg/g) compared to Z4T4L4 (33.6 μg/g and 46.1 μg/g, respectively). Despite lower skin levels, Z4T4L4 produced higher F% (lidocaine: 1.98% vs. 1.41%; tetracaine: 3.34% vs. 1.26%). The time to maximum plasma concentration (T_max) for lidocaine was found to be 2–4 h (Pliaglis) and 2–8 h (Z4T4L4), while for tetracaine, it was 1–8 h (Pliaglis) and 2–8 h (Z4T4L4). Conclusions: In this preliminary study, which included three subjects, Z4T4L4 exhibited a numerical tendency towards increased systemic bioavailability in comparison with Pliaglis. This observation was noted despite the fact that Z4T4L4 resulted in markedly lower skin concentrations. Due to the exploratory nature of the pilot study (n = 3), observed differences are reported as numerical trends. The data suggest that Z4T4L4 may enhance systemic absorption while reducing skin retention, highlighting a potential formulation-dependent dissociation between local concentration and systemic bioavailability. These preliminary findings provide in vivo evidence of a divergence between eutectic-based tissue retention and enhancer-driven systemic flux. This highlights that formulation design fundamentally dictates the safety profile of local anesthetics, necessitating a balance between local efficacy and systemic safety. Full article

Objectives: Research on the antimicrobial effect of Hypericum plant constituents is very rarely accompanied by studies of the cytotoxic effect on cell lines. In the current study, besides microbiological tests, an investigation of the cytotoxicity of Hypericum active ingredients on five non-tumorigenic cell lines, as well as research into the effect on other factors of host homeostasis, was performed. Methods: The main methods applied included an MTT assay, the broth microdilution method (BMD), real-time PCR, live cell imaging with Hoechst dye, Western blot, an enzyme-linked immunosorbent assay (ELISA), and skin irritation test on rabbits. Results: The mean inhibitory concentrations (IC₅₀) of six selected agents—previously phytochemically characterized extracts and compounds—ranged from 0.63 to 48 µg/mL. Due to their strong antimicrobial effect and favorable cytotoxic profile, the extract RochC from Hypericum rochelii and the compound olympiforin B from Hypericum olympicum were selected for subsequent studies at their previously determined minimum inhibitory concentrations (MICs) against Staphylococcus aureus—0.625 and 1 µg/mL, respectively. These doses were lower than their IC₅₀ values and the maximum tolerated concentrations (MTCs), according to ISO 10993-5, Annex C, for fibroblast cells, including a human gingival line. The MIC values of RochC and Olympiforin B against the cariogenic Streptococcus mutans were 6 and 3 µg/mL, respectively, values lower than the IC₅₀ values of the gingival cells. Olympiforin B inhibited the gene expression of the staphylococcal biofilm-related genes icaA and icaD, while RochC induced icaA and had a versatile effect on icaD. The MIC values for lactobacilli strains were higher than for S. aureus. The phytoconstituents did not cause cytopathic effects or apoptosis in CCL-1 fibroblasts at 2 × MIC. However, the agents at 1 × MIC significantly induced Atg5 and Atg7, proteins related to autophagy. Cytochrome P450 was not induced in liver cells, with the exception of a dose of 2 × MIC of RochC. The agents did not irritate rabbit skin in vivo at a dose of even 10 × MIC. Conclusions: The extract and compound have potential for further pharmacological development. Full article

The neuropeptide’s multifaceted involvement in various components of neural homeostasis impacts pain and behavioral regulation. One of the highly potent neuropeptides is dermorphin, extracted from the skin of the Amazon frog (Phyllomedusa sauvagei). The unique feature of dermorphin is the D-Ala residue in its sequence, which has inspired researchers to search for dermorphin analogs for use as pharmaceuticals. The primary objective of this study is to synthesize several new linear and cyclic dermorphin analogs and evaluate them as potential non-invasive analgesics. By exploring our method for converting linear peptides into 2,5-diketopiperazine(2,5-DKP) derivatives, which stabilize peptide structures, we synthesize several new dermorphin linear peptides and chimeric cyclopeptidomimetics. These compounds were tested in vitro and in vivo to determine their biological activities and potential applicability as pharmaceuticals. For the evaluation of in vitro opioid activity, the “Guinea Pig Ileum” (GPI) test was used. D2 showed the highest activity, and cyclopeptides D3 and D4 showed high activity. We can assume that dermorphin analogues D2, D3, and D4 are potent agonists of µ-type opioid receptors and have high opioid activity. However, this needs to be verified using molecular modeling methods in further research. The analgesic effects of dermorphins have been evaluated in the “Hot-Plate” and “Tail-Flick” tests. In rats, D2 dermorphin analogues demonstrated dose-dependent analgesic effect in the “Water Tail-Flick” test after intranasal administration. A smaller dose of 0.5 µg/kg resulted in 40% analgesia and a short-term state of stupor. The maximum long-lasting analgesia was observed at a dose of 1.0 µg/kg, which induced complete stupor. The analgesic effect of peptide D2 after intraperitoneal administration at a 5.0 mg/kg dose was over 50%. The “Open-Field” test demonstrated a dose-dependent (15, 50, 150 μg/kg) peptide D2 suppression effect on behavioural reactions in rats following intranasal administration. A new modification of linear peptides, combined with a 2,5-DKP scaffold (D3 and D4), proved promising for oral use based on the results of analgesic effect evaluation in mice following intragastric administration. Full article

Healthy Yellow River carp (Cyprinus carpio haematopterus) reared at a water temperature of 23 ± 0.6 °C were orally administered albendazole (ABZ) at a dose of 12 mg/kg body weight (BW) once daily for seven consecutive days. At predetermined time points after the final administration, five fish were randomly selected for sampling. Plasma, skin-on-muscle, liver, and kidney tissues were collected, and the concentrations of ABZ and its three metabolites—albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO₂), and albendazole-2-aminosulfone (ABZ-2-NH₂−SO₂)—were determined using high-performance liquid chromatography (HPLC). The results indicated that ABZ and ABZSO were widely distributed across tissues, while ABZSO₂ and ABZ-2-NH₂-SO₂ were only present at trace levels. Pharmacokinetic analysis of ABZ and ABZSO in plasma and tissues was performed using noncompartmental analysis (NCA). ABZ peaked in plasma at 0.73 μg/mL at 24 h after the last administration, with an elimination half-life (t_1/2λZ) of 38.56 h. ABZSO reached a peak plasma concentration of 1.54 μg/mL at 24 h, with a t_1/2λZ of 53.73 h. According to China’s national standard, where ABZ-2-NH₂−SO₂ is the marker residue with a maximum residue limit (MRL) of 100 μg/kg in fish skin-on muscle, no withdrawal period was necessary. However, based on the European Union standard—which uses the sum of ABZ and its three metabolites as the marker residue and an MRL of 100 μg/kg in ruminants—a withdrawal period of 16 days (or 351 °C-days) was required. Additionally, the study assessed changes in the intestinal microbiota following multiple oral doses of ABZ. The results indicated that ABZ administration significantly altered microbial diversity and composition in a dose- and time-dependent manner. After drug withdrawal, the intestinal microbiota gradually returned to baseline levels, similar to the untreated control group. Full article

Sulfamethoxazole (SMZ), a widely used broad-spectrum antibiotic in aquaculture, lacks comprehensive research on its residual elimination kinetics in tilapia. This study investigated SMZ residue depletion, withdrawal periods, and dietary risks in 1-year-old GIFT tilapia (Genetically Improved Farmed Tilapia Oreochromis niloticus) weighing 500 ± 50 g, following oral gavage administration of a loading dose (200 mg/kg BW on day 1) and then 100 mg/kg BW daily for 6 more days, at 22 ± 2 °C. Tissue samples (plasma, muscle, skin, liver, kidney, gill, and remaining tissues) were collected from five fish per time point at intervals from 0.33 to 30 days post-administration, with SMZ residues quantified via HPLC-MS/MS. Results revealed peak SMZ concentrations at 0.33 days (8 h), ordered as liver > skin > plasma > kidney > remaining tissues > gill > muscle. Muscle residues fell below the maximum residue limit (MRL, 100 μg/kg) by day 3, while skin required 10 days. Kidney residues dropped below the limit of detection (LOD) earliest (16 days), followed by muscle, gill, and remaining tissues (25 days), whereas plasma, liver, and skin retained detectable levels until day 30. Elimination equations for SMZ across tissues exhibited first-order kinetics. Based on the specific conditions of this study, a minimum 11-day withdrawal period is recommended for edible tissues (muscle + skin) after SMZ administration. Hazard quotient (HQ) values for all tissues remained below the safety threshold (HQ = 1), indicating low dietary risk. These findings support SMZ use standardization in tilapia aquaculture to ensure food safety compliance. Full article

Background/Objectives: The use of a patient-specific bolus in radiation therapy is critical for achieving precise dose delivery, particularly for irregular anatomical surfaces. Conventional boluses often suffer from poor conformity and air gaps, leading to suboptimal dose distribution. This study aimed to develop and evaluate a novel bolus fabrication method using the mold-and-casting (M&C) technique, which integrates 3D printing and flexible silicone materials to address these limitations. Methods: The proposed workflow includes CT imaging, 3D modeling, mold fabrication via 3D printing, and silicone casting to produce a patient-specific bolus. The process is followed by quality assurance steps and clinical application. Geometric accuracy was assessed through surface matching and cross-sectional comparisons, and dosimetric performance was evaluated using in vivo measurements with MOSFET detectors. The biocompatibility of the silicone material was tested according to standardized cytotoxicity, skin sensitization, and irritation protocols. Results: The fabricated boluses demonstrated high geometric fidelity, with volumetric and surface discrepancies of less than 3% compared to the planned structures. Dosimetric evaluations indicated that maximum dose differences remained within the clinically acceptable range of ±5%, confirming accurate dose delivery. Biocompatibility tests confirmed that the silicone material is safe for clinical use. Conclusions: The M&C method offers a streamlined approach to patient-specific bolus fabrication that integrates well into existing clinical workflows. Compared to traditional sheet boluses, it significantly reduces air gaps and enhances surface dose uniformity. These findings support the clinical potential of this technique to improve both precision and efficiency in radiation therapy. Full article

Natural products and botanicals continue to play a very important role in the development of cosmetics worldwide. The chemical constituents of a fine active fraction of the whole plant extract of Cuphea hookeriana Walp., and the tyrosinase and matrix metalloproteinase-1 (MMP-1) inhibitory and antioxidant activities of this fraction were investigated. The fine active fraction was mainly composed of seven natural compounds. The fine active fraction demonstrated substantial in vitro antioxidant potential using the ABTS assay (IC₅₀ 1.66 μg/mL). It inhibited the two target enzymes (tyrosinase and MMP-1) engaged in skin whitening and aging with comparable IC₅₀ values to the reference drugs. Acute toxicity experiments showed that mice gavage orally with the fine active fraction had no significant animal toxicity at a dose of 2000 mg/kg, and the maximum tolerated dose (MTD) in mice was greater than 2000 mg/kg. In a model where ultraviolet light promotes the increase in melanin secretion in guinea pig skin tissues, both α-arbutin and the fine active fraction can reduce melanogenesis, and the effect of the fine active fraction is better than that of α-arbutin. Full article

Background/Objectives: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) greatly complicates the treatment of skin and soft tissue infections (SSTI). It was previously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator complement peptide-derived immunostimulant-02 (CPDI-02; formerly EP67) increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection. Methods: Female CD-1 mice were challenged SQ with CA-MRSA USA300 LAC, then CPDI-02 or inactive scCPDI-02 was administered by a topical, SQ, IM, or IV route at 6 or 24 h post-challenge. Abscess sizes were compared over 10 days and CA-MRSA burden, neutrophils, MP, and pro-inflammatory cytokines were compared in subcutaneous abscesses. CPDI-02 PK and distribution in female CD-1 mice were compared after IM or IV dosing and CPDI-02 toxicity in male and female CD-1 mice was determined by IM dose escalation and repeat IM dosing. Results: Repeat IM treatment starting at 6 h post-challenge decreased maximum abscess surface area, CA-MRSA burden, and time to resolution, whereas repeat treatment by a topical, SQ, or IV route had no effect. Repeat treatment starting at 24 h post-challenge was ineffective by the current routes. Single IM treatment starting at 6 h post-challenge was as effective as repeat IM treatment, increased systemic exposure to CPDI-02, and, in subcutaneous abscesses, initially decreased IL-1β and increased MP. CPDI-02 was tolerated between 130 and 170 mg/kg after IM dose escalation and between 65 and 130 mg/kg after repeat IM dosing with males being more tolerant. Conclusions: Single early-stage IM treatment with CPDI-02 may increase curative protection against SSTI caused by CA-MRSA and/or other pathogens controlled by activated MP. Full article

Liposomal drug delivery systems are successfully used in various fields of medicine for external and systemic applications. Marine organisms contain biologically active substances that have a unique structure and exhibit a wide range of biological activities. Polysaccharide of red seaweed (carrageenan (CRG)), and water-insoluble sea urchin pigment (echinochrome (Ech)) interact with each other and form a stable complex. We included the CRG/Ech complex in liposomes for better permeability into cells. In our research, tetramethylrhodamine isothiocyanate TRITC-labeled CRG was synthesized to study the interaction of the complex encapsulated in liposomes with human epidermal keratinocytes (HaCaTs) widely used to expose the skin to a variety of substances. Using confocal microscopy, we found that liposomes were able to penetrate HaCaT cells with maximum efficiency within 24 h, and pre-incubation of keratinocytes with liposomes resulted in the delivery of the CRG/Ech complex into the cytoplasm. We investigated the anti-inflammatory effects of liposomes, including the lysosomal regulation, increased intracellular ROS levels, and increased NO synthesis in lipopolysaccharide (LPS)- or Escherichia coli (E. coli)-induced inflamed skin cells. Liposomes containing the CRG/Ech complex significantly reduced lysosomal activity by 26% in LPS-treated keratinocytes and decreased ROS levels in cells by 23% after LPS exposure. It was found that liposomes with the complex improved the migration of HaCaT keratinocytes incubated with high-dose LPS by 47%. The results of the work, taking into account the good permeability of liposomes into keratinocytes, as well as the anti-inflammatory effect on cells treated with LPS or E. coli, show the prospects of using liposomes containing the CRG/Ech complex as an anti-inflammatory agent in the fight against skin infections. Full article