Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

Synthesis of new trypanocidal agents from the hybridisation of metronidazole and eugenol analogues.

Nitroimidazole compounds are well-known bioactive substances, and the structural activity relationship has been reported whereby the position of the nitro group within the imidazole ring has a large influence on the activity. This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds). The in vitro trypanocidal tests show good results for both AC and AD hybrid compounds against both epimastigote and trypomastigote forms of T. cruzi. In silico studies showed positive data for most of the synthesised compounds and, in general present low toxicological risks. The AC compounds present lower ClogP (lipophilicity) values than those found for the AD series and higher TPSA (topological polar surface area) values, suggesting lower lipophilicity may be related to the presence of the triazole connector. The AD series compounds have higher Drug Score values than the AC series derivatives, suggesting better general properties for a pharmacological action.

Antimicrobial Activity of Syzygium aromaticum Essential Oil in Human Health Treatment.

The use of natural compounds to prevent and treat infective diseases is increasing its importance, especially in the case of multidrug-resistant (MDR) microorganisms-mediated infections. The drug resistance phenomenon is today a global problem, so it is important to have available substances able to counteract MDR infections. Syzygium aromaticum (L.) Merr. & L.M. Perry (commonly called clove) is a spice characterized by several biological properties. Clove essential oil (EO) consists of numerous active molecules, being eugenol as the principal component; however, other compounds that synergize with each other are responsible for the biological properties of the EO. S. aromaticum is traditionally used for bowel and stomach disorders, cold and flu, oral hygiene, tooth decay, and for its analgesic action. Its EO has shown antioxidant, antimicrobial, anti-inflammatory, neuro-protective, anti-stress, anticancer, and anti-nociceptive activities. This review aims to investigate the role of E. S. aromaticum EO in the counteraction of MDR microorganisms responsible for human disorders, diseases, or infections, such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi, Candida albicans, Giardia lamblia, Streptococcus mutans, Porphyromonas gingivalis, and Klebsiella pneumoniae. This study might orient clinical researchers on future therapeutic uses of S. aromaticum EO in the prevention and treatment of infectious diseases.

Less is more: Fewer attract-and-kill sites improve the male annihilation technique against Bactrocera dorsalis (Diptera: Tephritidae).

The Male Annihilation Technique (also termed the Male Attraction Technique; "MAT") is often used to eradicate pestiferous tephritid fruit flies, such as Bactrocera dorsalis (Hendel). MAT involves the application of male-specific attractants combined with an insecticide in spots or stations across an area to reduce the male population to such a low level that suppression or eradication is achieved. Currently, implementations of MAT in California and Florida targeting B. dorsalis utilize the male attractant methyl eugenol (ME) accompanied with a toxicant, such as spinosad, mixed into a waxy, inert emulsion STATIC ME (termed here "SPLAT-MAT-ME"). While highly effective against ME-responding species, such applications are expensive owing largely to the high cost of the carrier matrix and labor for application. Until recently the accepted protocol called for the application of approximately 230 SPLAT-MAT-ME spots per km2; however, findings from Hawaii suggest a lower density may be more effective. The present study adopted the methods of that earlier work and estimated kill rates of released B. dorsalis under varying spot densities in areas of California and Florida that have had recent incursions of this invasive species. Specifically, we directly compared trap captures of sterilized marked B. dorsalis males released in different plots under three experimental SPLAT-MAT-ME densities (50, 110, and 230 per km2) in Huntington Beach, CA; Anaheim, CA; and Sarasota-Bradenton, FL. The plots with a density of 110 sites per km2 had a significantly higher recapture proportion than plots with 50 or 230 sites per km2. This result suggests that large amounts of male attractant may reduce the ability of males to locate the source of the odor, thus lowering kill rates and the effectiveness of eradication efforts. Eradication programs would directly benefit from reduced costs and improved eradication effectiveness by reducing the application density of SPLAT-MAT-ME.

Artificial Biosynthetic Pathway for Efficient Synthesis of Vanillin, a Feruloyl-CoA-Derived Natural Product from Eugenol.

Eugenol, the main component of essential oil from the Syzygium aromaticum clove tree, has great potential as an alternative bioresource feedstock for biosynthesis purposes. Although eugenol degradation to ferulic acid was investigated, an efficient method for directly converting eugenol to targeted natural products has not been established. Herein we identified the inherent inhibitions by simply combining the previously reported ferulic acid biosynthetic pathway and vanillin biosynthetic pathway. To overcome this, we developed a novel biosynthetic pathway for converting eugenol into vanillin, by introducing cinnamoyl-CoA reductase (CCR), which catalyzes conversion of coniferyl aldehyde to feruloyl-CoA. This approach bypasses the need for two catalysts, namely coniferyl aldehyde dehydrogenase and feruloyl-CoA synthetase, thereby eliminating inhibition while simplifying the pathway. To further improve efficiency, we enhanced CCR catalytic efficiency via directed evolution and leveraged an artificialvanillin biosensor for high-throughput screening. Switching the cofactor preference of CCR from NADP+ to NAD+ significantly improved pathway efficiency. This newly designed pathway provides an alternative strategy for efficiently biosynthesizing feruloyl-CoA-derived natural products using eugenol.

Development of an allele-specific PCR (AS-PCR) method for identifying high-methyl eugenol-containing purple Tulsi (Ocimum tenuiflorum L.) in market samples.

BACKGROUND: Ocimum tenuiflorum L. is a highly traded medicinal with several therapeutic values. Green Tulsi and purple Tulsi are two subtypes in O. tenuiflorum and both have the same medicinal properties. Recent reports have revealed that purple Tulsi contains higher quantities of methyl eugenol (ME), which is moderately toxic and potentially carcinogenic. Therefore, we developed an allele-specific PCR (AS-PCR) method to distinguish the green and purple Tulsi. METHODS AND RESULT: Using the green Tulsi as a reference, 12 single nucleotide polymorphisms (SNPs) and 10 insertions/deletions (InDels) were identified in the chloroplast genome of the purple Tulsi. The C > T SNP at the 1,26,029 position in the ycf1 gene was selected for the development of the AS-PCR method. The primers were designed to amplify 521 bp and 291 bp fragments specific to green and purple Tulsi, respectively. This AS-PCR method was validated in 10 accessions from each subtype and subsequently verified using Sanger sequencing. Subsequently, 30 Tulsi powder samples collected from the market were subjected to molecular identification by AS-PCR. The results showed that 80% of the samples were purple Tulsi, and only 3.5% were green Tulsi. About 10% of the samples were a mixture of both green and purple Tulsi. Two samples (6.5%) did not contain O. tenuiflorum and were identified as O. gratissimum. CONCLUSION: The market samples of Tulsi were predominantly derived from purple Tulsi. The AS-PCR method will be helpful for quality control and market surveillance of Tulsi herbal powders.

Active cellulose acetate/purple sweet potato anthocyanins@cyclodextrin metal-organic framework/eugenol colorimetric film for pork preservation.

As a natural pH-sensing colorant, purple sweet potato anthocyanins (PSPAs) have demonstrated great potential in colorimetric film for freshness monitoring. However, the photothermal instability of PSPAs is still a challengeable issue. Herein, γ-cyclodextrin metal-organic framework (CD-MOF) loaded with PSPAs (PSPAs@CD-MOF, i.e., PM) and eugenol (EUG) were incorporated in cellulose acetate (CA) matrix for developing a smart active colorimetric film of CA/PM/EUG, where PM and EUG were hydrogen-bonded with CA. Attentions were focused on the photothermal colorimetric stability, colorimetric response, and antibacterial activity of the films. The presence of PM and EUG endowed the film outstanding UV-blocking performance and enhanced the barrier against water vapor and oxygen. Target film of CA/PM15/EUG10 had good photothermal colorimetric stability due to the protection of CD-MOF on PSPAs and the color changes with pH-stimuli were sensitive and reversible. In addition to antioxidant activity, CA/PM15/EUG10 had antibacterial activity against Escherichia coli and Staphylococcus aureus. The application trial results indicated that the CA/PM15/EUG10 was valid to indicate pork freshness and extended the shelf-life by 100 % at 25 °C, which has demonstrated a good perspective on smart active packaging for freshness monitoring and shelf-life extension.

A Promising Plant-Based Eugenol-Loaded Nano Delivery System (EUG@CMC-PGMA-CS) for Enhanced Antibacterial and Insect Repellent Behavior.

Pathogens and pests pose significant threats to global crop productivity and plant immunity, necessitating urgent measures from researchers to prevent pathogen contamination and pest damage to crops. A natural plant-based antibacterial agent, eugenol (EUG), has demonstrated excellent antimicrobial and insect repellent capabilities, but the characteristics of volatilization and poor dissolution limit the practical application. The nanoization of pesticide formulations holds promise in the development of highly effective pesticides for antibacterial and insecticidal purposes. Herein, a eugenol-loaded nano delivery system (EUG@CMC-PGMA-CS) was synthesized using glycidyl methacrylate (GMA) as a functional monomer to connect carrier core structure carboxymethyl cellulose (CMC) with shell structure chitosan (CS), and EUG was encapsulated within the carrier. EUG@CMC-PGMA-CS demonstrated excellent leaf affinity, with minimum contact angles (CAs) of 37.83 and 70.52° on hydrophilic and hydrophobic vegetable leaf surfaces, respectively. Moreover, the maximum liquid holding capacity (LHC) of EUG@CMC-PGMA-CS on both hydrophilic and hydrophobic vegetable leaf surfaces demonstrates a noteworthy 55.24% enhancement compared to the LHC of pure EUG. The in vitro release curve of EUG@CMC-PGMA-CS exhibited an initial burst followed by stable sustained release. It is with satisfaction that the nano delivery system demonstrated exceptional antibacterial properties against S. aureus and satisfactory insecticidal efficacy against Spodoptera litura. The development of this eugenol-loaded nano delivery system holds significant potential for enhanced antibacterial and insect repellents in agriculture, paving the way for the application of volatile bioactive substances.

Combinatorial effects between aromatic plant compounds and chlorhexidine digluconate against canine otitis-related Staphylococcus spp.

The increasing prevalence of antimicrobial resistance among bacterial pathogens necessitates novel treatment strategies, particularly in veterinary medicine where otitis in dogs is very common in small animals' clinical routines. Considering this challenge, this study explores the efficacy of aromatic plant compounds (APC), including eugenol (EUG), trans-cinnamaldehyde (TC), and geraniol (GER), and their synergistic potential when combined with the antiseptic agent chlorhexidine (CLX), offering insight into alternative therapeutic approaches. The disk diffusion assay revealed differential sensitivity of Staphylococcus spp. strains to the tested compounds, with EUG and GER showing moderate inhibition zones and TC displaying considerably larger inhibition zones. Further analysis through MIC and MBC determinations suggested that EUG required the highest concentrations to inhibit and kill the bacteria, whereas TC and GER were effective at lower concentrations. Combined with CLX, all three plant-derived compounds demonstrated a significant enhancement of antibacterial activity, indicated by reduced MIC values and a predominantly synergistic interaction across the strains tested. GER was the most potent in combination with CLX, presenting the lowest mean FICi values and the highest fold reductions in MIC. This study emphasizes the APC's potential as an adjunct to conventional antimicrobial agents like CLX. The marked synergy observed, especially with GER, suggests that such combinations could be promising alternatives in managing bacterial otitis in dogs, potentially mitigating the impact of antibiotic resistance.

A novel perspective on eugenol as a natural anti-quorum sensing molecule against Serratia sp.

Serratia marcescens is commonly noted to be an opportunistic pathogen and is often associated with nosocomial infections. In addition to its high antibiotic resistance, it exhibits a wide range of virulence factors that confer pathogenicity. Targeting quorum sensing (QS) presents a potential therapeutic strategy for treating bacterial infections caused by S. marcescens, as it regulates the expression of various virulence factors. Inhibiting QS can effectively neutralize S. marcescens' bacterial virulence without exerting stress on bacterial growth, facilitating bacterial eradication by the immune system. In this study, the antibacterial and anti-virulence properties of eugenol against Serratia sp. were investigated. Eugenol exhibited inhibitory effects on the growth of Serratia, with a minimal inhibitory concentration (MIC) value of 16.15 mM. At sub-inhibitory concentrations, eugenol also demonstrated antiadhesive and eradication activities by inhibiting biofilm formation. Furthermore, it reduced prodigiosin production and completely inhibited protease production. Additionally, eugenol effectively decreased swimming and swarming motilities in Serratia sp. This study demonstrated through molecular modeling, docking and molecular dynamic that eugenol inhibited biofilm formation and virulence factor production in Serratia by binding to the SmaR receptor and blocking the formation of the HSL-SmaR complex. The binding of eugenol to SmaR modulates biofilm formation and virulence factor production by Serratia sp. These findings highlight the potential of eugenol as a promising agent to combat S. marcescens infections by targeting its virulence factors through quorum sensing inhibition.

Antimicrobial activity of eugenol and carvacrol against Salmonella enterica and E. coli O157:H7 in falafel paste at different storage temperatures.

The objectives of the current study were: i) to investigate the antimicrobial activity of 0.125, 0.250 and 0.50 % (7.54, 15.08 and 30.17 mmol/Kg of eugenol) and (8.15, 16.31, and 33.61 mmol/Kg of carvacrol) against S. enterica and E. coli O157:H7 in falafel paste (FP) stored at 4, 10 or 25 °C for 10 d; and ii) to study the sensory properties of fried falafel treated with eugenol and carvacrol. S. enterica grew well in untreated falafel (control) samples at 10 and 25 °C, while E. coli O157:H7 grew only at 25 °C. However, numbers of S. enterica and E. coli O157:H7 in FP stored at 4 °C were reduced by 1.4-1.6 log CFU/g after 10 d. The antimicrobial agents were more effective at 25 °C against S. enterica, but were better at 4 and 10 °C against E. coli O157:H7. Addition of 0.125-0.5 % eugenol or carvacrol reduced the S. enterica numbers to undetectable level by direct plating (2 log CFU/g) by 2-10 d at 25 °C. FP samples treated with 0.5 % eugenol or 0.25-0.5 % carvacrol were negative for S. enterica cells by enrichment (1 CFU/5 g) by 10 d at 25 °C. In contrast, viable E. coli O157:H7 were not detected by direct plating when FP was treated with 0.25-0.5 % carvacrol or 0.5 % eugenol and stored at 4 °C by 2 d. Addition of eugenol or carvacrol did not affect the color, texture, and appearance of fried falafel but decreased the flavor and overall acceptability scores compared to untreated falafel. Using eugenol and carvacrol as natural antimicrobials have the potential to enhance the safety of FP by reducing the threat from foodborne pathogens.

Assessment of acute and subacute toxicity, pharmacokinetics, and biodistribution of eugenol nanoparticles after oral exposure in Wistar rats.

The present study aimed to assess the safety, toxicity, biodistribution, and pharmacokinetics of eugenol nanoparticles (EONs) following oral administration in Wistar rat models. In the acute toxicity study, the rats were given a fixed dose of 50, 300, and 2000 mg/kg body weight per group orally and screened for 2 weeks after administration. In the subacute study, three different doses (500, 1000, and 2000 mg/kg BW) of EON were administered for 28 days. The results indicated no significant differences in food and water consumption, bodyweight change, hematological and biochemical parameters, relative organ weights, gross findings, or histopathology compared to the control. Additionally, no significant changes were observed in the expression profiles of inflammatory cytokines such as IL-1, IL-6, and TNFα in the plasma, confirming the absence of systemic inflammation. Biodistribution analysis revealed rapid absorption of eugenol and improved bioavailability due to gradual and sustained release, leading to a maximum eugenol concentration of 15.05 µg/mL (Cmax) at approximately 8 h (Tmax) in the blood plasma. Thus, the study provides valuable insights into the utilization of EON for enhancing the stability, solubility, and sustained release of eugenol and highlights its promising safety profile in vivo.

Phosphoproteomics analysis reveals the anti-bacterial and anti-virulence mechanism of eugenol against Staphylococcus aureus and its application in meat products.

The increasing risk of food poisoning caused by Staphylococcus aureus (S. aureus) contamination has aroused great concern about food safety. Eugenol is highly favored due to its broad-spectrum antibacterial activity and non-drug resistance property. The study aimed to reveal the anti-bacterial and anti-virulence mechanisms of eugenol against S. aureus using phosphoproteomics. The results indicated that eugenol could inhibit the phosphorylation levels of enzyme I in the bacterial phosphotransferase system (PTS). Meanwhile, it could also inhibit the phosphorylation levels of key enzymes in bacterial carbon metabolism (such as glucose-6-phosphate isomerase of glycolysis and succinyl-CoA synthetase of tricarboxylic acid cycle), thereby decreasing the content of ATP and accelerating bacterial death. In addition, eugenol could inhibit the phosphorylation of AgrA in the quorum sensing system, thereby inhibiting the expression of agr operons (agrA and agrC) and downstream virulence genes (RNAIII, hla and seb). Finally, the application on beef indicated that eugenol could effectively decrease the content of enterotoxins and improve its storage quality. These findings provide a new way for eugenol to prevent S. aureus contamination and food poisoning in meat products.

Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models.

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 µM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

Multi-Omics Approaches for Liver Reveal the Thromboprophylaxis Mechanism of Aspirin Eugenol Ester in Rat Thrombosis Model.

Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE had excellent thromboprophylaxis and inhibition of platelet aggregation. This study aimed to investigate the effect of AEE on the liver of thrombosed rats to reveal its mechanism of thromboprophylaxis. Therefore, a multi-omics approach was used to analyze the liver. Transcriptome results showed 132 differentially expressed genes (DEGs) in the AEE group compared to the model group. Proteome results showed that 159 differentially expressed proteins (DEPs) were identified in the AEE group compared to the model group. Six proteins including fibrinogen alpha chain (Fga), fibrinogen gamma chain (Fgg), fibrinogen beta chain (Fgb), orosomucoid 1 (Orm1), hemopexin (Hpx), and kininogen-2 (Kng2) were selected for parallel reaction monitoring (PRM) analysis. The results showed that the expression of all six proteins was upregulated in the model group compared with the control group. In turn, AEE reversed the upregulation trend of these proteins to some degree. Metabolome results showed that 17 metabolites were upregulated and 38 were downregulated in the model group compared to the control group. AEE could reverse the expression of these metabolites to some degree and make them back to normal levels. The metabolites were mainly involved in metabolic pathways, including linoleic acid metabolism, arachidonic acid metabolism, and the tricarboxylic acid (TCA) cycle. Comprehensive analyses showed that AEE could prevent thrombosis by inhibiting platelet activation, decreasing inflammation, and regulating amino acid and energy metabolism. In conclusion, AEE can have a positive effect on thrombosis-related diseases.

Dietary Isoeugenol Supplementation Attenuates Chronic UVB-Induced Skin Photoaging and Modulates Gut Microbiota in Mice.

Photoaging, the primary cause of skin aging damage, results from chronic ultraviolet (UV) exposure, leading to dryness and wrinkle formation. Nutritional intervention has emerged as a practical approach for preventing and addressing the effect of skin photoaging. The primary aromatic compound isolated from clove oil, isoeugenol (IE), has antibacterial, anti-inflammatory, and antioxidant qualities that work to effectively restrict skin cancer cell proliferation. This investigation delved into the advantages of IE in alleviating skin photoaging using UVB-irradiated skin fibroblasts and female SKH-1 hairless mouse models. IE alleviated UVB-induced photodamage in Hs68 dermal fibroblasts by inhibiting matrix metalloproteinase secretion and promoting extracellular matrix synthesis. In photoaged mice, dietary IE reduced wrinkles, relieved skin dryness, inhibited epidermal thickening, and prevented collagen loss. Additionally, the intestinal dysbiosis caused by prolonged UVB exposure was reduced with an IE intervention. The results of Spearman's analysis showed a strong correlation between skin photoaging and gut microbiota. Given the almost unavoidable UVB exposure in contemporary living, this research demonstrated the efficacy of dietary IE in reversing skin photoaging, presenting a promising approach to tackle concerns related to extrinsic skin aging.

Cornstarch aerogels with thymol, citronellol, carvacrol, and eugenol prepared by supercritical CO2- assisted techniques for potential biomedical applications.

This study focuses on the development of bioactive materials using environmentally friendly techniques, renewable, biocompatible, and biodegradable polysaccharide, as well as natural bioactive compounds (NBCs) found in plant extracts. First, cornstarch aerogels with a porosity of 86 % and a specific surface area of 225 m2/g were produced via supercritical CO2- assisted drying. Further, thymol, citronellol, carvacrol, and eugenol were incorporated into the aerogels by supercritical CO2- assisted impregnation, which allowed variation in loadings of NBCs (12.8-17.6 %). Interaction between cornstarch aerogels and NBCs determined impregnation rate, pore wall thickness (in the range 18-95 nm), liquid absorption capacity (from 265 to 569 %), dehydration mass loss, and release in phosphate-buffered saline. Controlled release of NBCs was maintained over a 3-day period. Moreover, impregnated aerogels showed a significant antioxidant effect with the highest value for DPPH radical inhibition of 25.5 % determined for the aerogels impregnated with eugenol. Notable antimicrobial activity against tested Gram-negative bacteria, Gram-positive bacteria, and fungi was also observed, being the highest for thymol-loaded aerogel with the diameter of the inhibition zones of up to 37.5 mm. This work shows a promising green approach for the production of bioactive two-component starch-based materials for potential applications in skin infection treatment.