Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is an agricultural pest of global economic importance. Its ability to reproduce, adapt, and develop resistance necessitates the creation of effective and environmentally friendly alternative control strategies. This study aimed to evaluate the larvicidal activity of three nanoformulations (NFs) based on the essential oil (70% safrole) of Piper auritum Kunth (Piperales: Piperaceae), nanoemulsion (NE), microemulsion (ME), and silver nanoparticles (AgNPs), against second-instar larvae of S. frugiperda. The NFs were prepared using a combination of low- and high-energy methods, using Tween 80 and Span 80 as stabilizing agents. The droplet sizes of the NFs ranged from 19 to 48 nm. Stability analysis of the formulations maintained for 60 days in open systems at room temperature allowed the identification of remaining oxidized sesquiterpenes and phenylpropanoids. In in vitro bioassays, the NE demonstrated the highest larvicidal activity, with an LD50 of 0.97 µg cm−2, outperforming the other formulations by a factor of ten. Observations of morphological damage to larval and pupal tissues, along with deformation of adult specimens, confirming the toxicity of the NFs. These findings highlight the potential of essential oil-based NFs derived from P. auritum as sustainable biopesticides for integrated pest management.

Ulcerative colitis (UC) is a chronic inflammatory colon disease that is a major public health problem. The long-term administration of traditional drugs is likely to trigger adverse reactions. The myrrh essential oil (MEO) exhibits promising therapeutic efficacy against ulcerative colitis. However, due to the inherent instability and volatility of MEO, it was formulated into myrrh essential oil microemulsion (MM) with the aim of enhancing its stability. This study explored the optimal formulation for synthesizing MM, and a series of relevant indices were employed to meticulously investigate its stability characteristics. In animal experiments, a UC mouse model was established with the assistance of Dextran Sulfate Sodium (DSS). The therapeutic efficacy was comprehensively evaluated by recording Disease Activity Index (DAI) scores, detecting the levels of Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β), and observing the morphological features of mouse colonic tissues through hematoxylin-eosin (HE) staining and immunohistochemistry (IHC) techniques. The results confirmed that both MEO and MM are effective in treating ulcerative colitis.

The development of advanced macromolecular systems with tailored structural and functional properties is a key objective in modern materials science, particularly for biomedical applications such as targeted drug delivery. In this study, hydrogel (HG), a polymer-based formulation, was investigated as a functional carrier for the enhanced intradermal and transdermal delivery of propranolol hydrochloride (PRO-HCl), a highly water-soluble model compound, and its potential was compared to other vehicles easily obtained by pharmacists: ointment (OM), liposomal cream (LCR), and microemulsion (ME). The formulations were characterized by their physicochemical and rheological characteristics, and evaluated in vitro and ex vivo using vertical diffusion cells equipped with synthetic membranes, intact porcine skin, and skin pretreated with solid microneedles (MNs). The HG formulation exhibited superior release performance (2396.85 ± 48.18 μg/cm2) and the highest intradermal drug deposition (19.87 ± 4.12 μg/cm2), while its combination with MNs significantly enhanced transdermal permeation (p = 0.0017). In contrast, the synergistic effect of MNs and ME led to a pronounced increase in drug accumulation within the skin (up to 60.3-fold). These findings highlight the crucial role of matrix composition and properties in modulating molecular transport through biological barriers. The study demonstrates that polymeric HGs represent versatile, functional materials with tunable structural and mechanical features, suitable for controlled release and potential systemic delivery applications.

Histopathological analysis reveals mild to moderate changes in BALB/c mice after short-term administration of a microemulsion loaded with epoxy-α-lapachone.

Skin aging is a complex process caused by oxidative stress, leading to a growing need for cosmeceuticals with effective antioxidant and matrix metalloproteinase-1 (MMP-1) inhibitory activities. D. formosum has shown various biological activities; however, an appropriate delivery system is required to enhance its efficacy. Our study firstly explored the protective effects of D. formosum extract on UVB-irradiated human keratinocytes (HaCaT) and human fibroblasts (BJ), and then developed topical microemulsion (ME) containing D. formosum extract. Our results show that D. formosum extract demonstrates anti-aging properties by reducing intracellular reactive oxygen species (ROS) in UVB-irradiated HaCaT and BJ, and inhibiting MMP-1 expression. Pseudo-ternary phase diagrams were constructed using the water titration method. The optimized microemulsion base (MEB) contained trilaureth-4 phosphate: propylene glycol (surfactant: cosurfactant; 2:1, 57.50%), isononyl isononanoate (oil, 17.50%), and deionized water (25.00%). The 0.40% w/w D. formosum extract, called DME1, was loaded into the MEB. This formulation exhibited desirable characteristics, including size, polydisperse index (PDI), zeta potential, and viscosity. DME1 was physicochemically and chemically stable. The DME1 also significantly increase skin retention and was safe to human skin cells. Our findings highlight D. formosum extract as a novel active ingredient and its potentially topical delivery for anti-aging purpose.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-26252-1.

Passiflora setacea seed oil is a natural source of bioactive unsaturated fatty acids, notably linoleic acid (ω-6) and oleic acid (ω-9), with promising antioxidant and anti-inflammatory potential for dermatological applications. However, its direct use is limited by poor physicochemical and organoleptic properties. This study aimed to develop and optimize a topical microemulsion (ME) system incorporating P. setacea seed oil using quality by design principles to address formulation challenges. The oil was extracted via Soxhlet and characterized by gas chromatography–mass spectrometry and thermal analysis. A full factorial design, followed by a Box–Behnken design, was employed to optimize the formulation based on critical quality attributes and the defined quality target product profile. The optimized ME presented a hydrodynamic diameter of approximately 22 nm and polydispersity index below 0.2 and remained stable for 60 days. The ME was gelled with sodium carboxymethyl cellulose, while vitamin E and Liquid Germall® Plus were incorporated as antioxidant and preservative agents, respectively, yielding the final topical gel formulation. Cytocompatibility assays demonstrated high cell viability for ME at concentrations below 2 mg/mL in RAW 264.7 macrophages and 0.5 mg/mL in human umbilical vein endothelial cells. Overall, this work presents a promising nanotechnology-based topical delivery platform for P. setacea seed oil, employing quality by design principles to ensure formulation performance, stability, and skin cell compatibility.

Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood–retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (Smix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a Smix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94–56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen’s egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections.

Mesosomes as sub-micrometer-sized emulsions containing internally self-assembled lyotropic liquid crystalline (LLC) mesophases were engineered using lactoferrin (LF) as a Pickering stabilizer. LF was pretreated with ultrasonication to prevent agglomeration and applied under controlled pH conditions during processing, resulting in emulsions with a positive surface charge and high stability. Glycerol monooleate (GMO) in mixtures with oleic acid (OA) at varying concentration ratios were used to produce four different lyotropic mesophases: bicontinuous cubic (Pn3m), inverse hexagonal (H2), inverse micellar cubic (Fd3m), and microemulsions (ME). At a preadjusted pH of 4, LF stabilized all four lyotropic mesophases via a Pickering-type mechanism, forming mesosomes with hydrodynamic diameters (dH) ranging from ∼187 to ∼239 nm, as measured by dynamic light scattering (DLS). High-pressure ultrasonication was used to drive positively charged LF to adsorb at the LLC-water interface, confirmed via confocal microscopy. The sonication led to a distinct positive surface charge on the mesosomes, as evidenced by the ζ potential of ∼+30 mV, without compromising the mesosomes' size and stability. Time-resolved DLS experiments showed that all mesosomes had long-term stability against coalescence and aggregation for at least 1 month of storage at room temperature. Small-angle X-ray scattering was used to study the phase behavior of GMO/OA mixtures before and after their stabilization by LF. The results showed that all four bulk mesophases maintained their structural hierarchy after being homogenized into mesosomes. Notably, pure GMO stabilized by LF formed cubosomes of diamond Pn3m, the same morphology as GMO in the bulk. This behavior is different from what has been observed for the commonly used stabilizer for LLC systems, Pluronic F127, which induces a transition to a primitive Im3m cubic morphology upon stabilization.

Anal fissures (AF) are painful anorectal disorders for which topical calcium-channel blockers (CCBs), such as amlodipine besylate (AMD), are recommended to avoid systemic adverse effects associated with oral therapy. However, the topical use of AMD has been limited by its poor aqueous solubility and chemical instability.This study focused on developing and characterizing a 1% w/w AMD-loaded microemulsion (ME) for topical application. Optimal composition was selected using solubility screening and pseudo-ternary phase diagrams. The lead formulation, M5, demonstrated favorable properties: nanometric scale (size ≈ 34 nm, PDI 0.45), pseudoplastic rheology (viscosity ≈20 Pa·s), and high interfacial stability (ζ - potential +8.7 mV).Franz diffusion cell assays confirmed sustained permeation (steady-state flux ≈14.4 µg·cm−2·min−1), while differential scanning calorimetry evidenced partial plasticization of AMD by the surfactant matrix. The final product was manufactured at pilot scale under GMP guidelines to ensure long-term stability. AMD potency decreased by only 7.7% over 24 months under refrigerated storage. In vitro safety evaluations confirmed a non-irritant profile and low acute toxicity.Compared with other reported topical CCB preparations, this AMD-loaded ME provides superior physicochemical stability, reproducible permeation, and dermal compatibility. These results establish a translational platform for future GMP-scale validation and clinical assessment in AF management.

ABSTRACTThis study investigated the use of Rosmarinus officinalis (rosemary) essential oil in a microemulsion (ME) formulation for the treatment of ocular fungal keratitis, a serious infection that can lead to blindness. The ME was characterized in terms of pH, stability, homogeneity, osmolarity, and other physicochemical properties. The Hen's Egg Test‐Chorioallantoic Membrane assay was used to assess ocular irritancy, and antifungal efficacy was evaluated using the minimum inhibitory concentration method. The oil extraction yielded 1.2%, with eucalyptol (37.89%) as the major compound. The formulation showed a suitable pH (6.96), particle size of 11.35 nm, good stability, and was classified as non‐irritant with an irritation score = 1.5. It exhibited strong antifungal activity against Candida parapsilosis (96.1%), C. krusei (100%), C. albicans (99.1%), Fusarium graminearum (90.5%), and Aspergillus parasiticus (79.5%). The results highlight the potential of rosemary essential oil as a base for developing eye drops for the treatment of fungal keratitis.

Development, characterization and in vitro assessment of a novel self-microemulsifying drug delivery system to increase cannabidiol intestinal bioaccessibility.

Background: Skin mycoses affect approximately 10% of the global population, and the range of effective topical antifungal agents remains limited. Voriconazole (VRC) is a broad-spectrum triazole with proven efficacy against drug-resistant fungal infections. This study aimed to develop and optimize VRC-loaded microemulsion (ME) polymer gels (Carbopol®-based) for cutaneous delivery. Selected formulations also contained menthol (2%) as a penetration enhancer and potential synergistic antifungal agent. Methods: A comprehensive screening was performed using pseudoternary phase diagrams to identify stable oil/surfactant/co-surfactant/water systems. Selected MEs were prepared with triacetin, Etocas™ 35, and Transcutol®, then gelled with Carbopol®. Formulations were characterized for pH, droplet size, polydispersity index (PDI), and viscosity. In vitro VRC release was assessed using diffusion cells, while ex vivo permeation and skin deposition studies were conducted on full-thickness human skin. Rheological behavior (flow curves, yield stress) and texture (spreadability) were evaluated. Antifungal activity was tested against standard strain of Candida albicans and clinical isolates including a fluconazole-resistant strain. Results: The optimized ME (pH ≈ 5.2; droplet size ≈ 2.8 nm) was clear and stable with both VRC and menthol. Gelation produced non-Newtonian, shear-thinning hydrogels with low thixotropy, favorable for topical application. In ex vivo studies, performed with human skin, both VRC-loaded gels deposited the drug in the epidermis and dermis, with no detectable amounts in the receptor phase after 24 h, indicating retention within the skin. Menthol increased VRC deposition. Antifungal testing showed that VRC-containing gels produced large inhibition zones against C. albicans, including the resistant isolate. The VRC–menthol gel exhibited significantly greater inhibition zones than the VRC-only gel, confirming synergistic activity. Conclusions: ME-based hydrogels effectively delivered VRC into the skin. Menthol enhanced drug deposition and demonstrated synergistic antifungal activity with voriconazole.

Abstract The oxidation of cyclohexane is a crucial bulk process to produce cyclohexanol and cyclohexanone (KA oil), used for the synthesis of adipic acid and further polyamide fibers and plastics production. The industrial process is carried out at high temperature in the presence of a cobalt‐based homogeneous catalyst, which no longer meets the sustainability requirements imposed by the increase of environmental concerns. This research aimed to investigate the potential of Co‐based heterogeneous catalysts, where Co is coupled with Fe. Fe has been selected considering its ability of decomposing hydroperoxides along with its oxidation‐reduction properties, which can help the homolytic cleavage of the cyclohexyl hydroperoxide intermediate in the cyclohexane oxidation. Heterogeneous Fe─Co catalysts supported on alumina have been thus synthesized by three different methods, i.e., sol‐immobilization (SOL), wetness impregnation (IW), and inverse microemulsion (ME). Fe‐ and Co‐ and the corresponding Fe 1 Co 1 /Al 2 O 3 catalysts prepared by different preparation methods resulted in different physical and morphological features and in turn in a different catalytic activity and selectivity toward cyclohexane oxidation. In particular, the synthesis by inverse microemulsion technique resulted in the highest metal dispersion, where Co was in contact with Fe. The highest dispersion of Co resulted in the highest activity, where the 2 wt% Co/γ‐Al 2 O 3 ‐ME was the most active catalyst, producing 5.1 mmol of KA oil after 5 h of reaction with a selectivity of 96.0%; on the other hand, the presence of Fe allowed to increase the selectivity, as the 2 wt% Fe 1 Co 1 /γ‐Al 2 O 3 ‐ME catalyst produced 4.7 mmol of KA oil after 5 h of reaction with a selectivity of 98.8%.

Optimization of astaxanthin extraction from red (Gracilaria corticata) and brown (Sargassum polycystum) macroalgae through ultrasonication and microwave processing

Cutaneous delivery and biodistribution of a lipophilic natural product - bakuchiol: Comparing nanocarrier performance.

Evidence for the formation of stable water pools within fluorous solvents (perfluorodecalin, perfluoromethylcyclohexane, and perfluorooctane) facilitated by a perfluorinated emulsifier perfluoroheptanoic acid (PFHA) under ambient conditions is presented. The presence of water-in-fluorous solvent (w/fluorous) microemulsions (MEs) is initially established with visual inspection and by constructing a pseudo-ternary phase diagram followed by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and FTIR absorbance data analysis. DLS and SAXS measurements show that the hydrodynamic diameter (Dh) and radius of gyration (Rg) increase significantly with increase in water content. The spherical model of fitting is found to be the most accurate in Guinier analysis, suggesting the MEs to be spherical in shape. FTIR absorbance spectral deconvolution reveals a decrease and increase in the relative population of bound and bulk-like water, respectively, as the water content is increased within the system. Solute solvation within w/fluorous MEs was investigated utilizing several structurally different (bio)molecular probes possessing varying optical spectroscopic signatures. Rotational reorientation times recovered from the excited-state fluorescence anisotropy decay indicate a decreasing trend with increasing water content, suggesting transport of rhodamine 6G and fluorescein Na salt from bulk media to the water pools where they are preferentially solvated. Excited-state proton transfer (ESPT) for pyranine and (-)-riboflavin also reveals the solvation of these probes within ME water pools. A common porphyrin, meso-tetrakis(4-sulfonatophenyl)porphyrin, readily undergoes J aggregation within the water pools. Protein, bovine serum albumin, preferentially solubilizes within the water pools of the w/fluorous MEs and effectively interacts with the pH indicator bromophenol blue. This w/fluorous ME medium with fluorous solvent as the bulk phase is bound to play a major role in the pulmonary drug delivery process and has potential to completely replace conventional VOC-based MEs across all applications.

Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two delivery systems, self-nanoemulsifying drug delivery systems (SNEDDS) and microemulsions (ME), to enhance their stability and fish anesthetic efficacy. Methods: The optimized SNEDDS (25% basil oil, 8.33% coconut oil, 54.76% Tween 80, 11.91% PEG 400) and ME (12% basil oil, 32% Tween 80, 4% sorbitol, 12% ethanol, 40% water) were characterized for droplet size, PDI, zeta potential, pH, and viscosity. Stability was evaluated by monitoring droplet size and PDI over time and by determining the retention of eugenol, methyl eugenol, and β-caryophyllene after storage at 45 °C. Fish anesthetic efficacy was tested in koi carp (Cyprinus carpio var. koi). Results: SNEDDS maintained a small droplet size (~22.78 ± 1.99 nm) and low PDI (0.188 ± 0.088 at day 60), while ME showed significant size enlargement (up to 177.10 ± 47.50 nm) and high PDI (>0.5). After 90 days at 45 °C, SNEDDS retained 94.45% eugenol, 94.08% methyl eugenol, and 88.55% β-caryophyllene, while ME preserved 104.76%, 103.53%, and 94.47%, respectively. In vivo testing showed that SNEDDS achieved faster anesthesia (114.70 ± 24.80 s at 120 ppm) and shorter recovery (379.60 ± 15.61 s) than ME (134.90 ± 4.70 s; 473.80 ± 16.94 s). Ethanol failed to induce anesthesia at 40 ppm and performed poorly compared to SNEDDS and ME at other concentrations (p < 0.0001). Conclusions: SNEDDS demonstrated superior physical stability and fish anesthetic performance compared to ME. These findings support SNEDDS as a promising formulation for delivering holy basil essential oil in biomedical and aquaculture applications.

Despite a marked decrease in HIV/AIDS-related mortality, HIV remains one of the leading causes of death in specific populations. Despite concerted efforts to find a cure for HIV, to date, none exists. Current antiretroviral therapy inhibits replication of the virus without completely eradicating it. The successful inhibition of viral replication is only achieved using a combination of antiretrovirals, which inhibit viral replication at different stages of the HIV lifecycle. Efavirenz (EFV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) is one combination used for HIV management. The development of a novel fixed-dose microemulsion formulation of EFV, FTC, and TDF was undertaken. Microemulsions (ME) were manufactured using phase titration and drug loading, particle size, transparency, Zeta potential, and pH were determined. Transmission Electron Microscopy was used to visualize the microemulsion. In vitro release testing was used to evaluate active pharmaceutical ingredient release behavior. The optimized ME had an average Zeta potential of 33.8 mV and droplet size of 117 nm, determined using Dynamic Light Scattering and confirmed using Transmission Electron Microscopy. Powder X-ray diffraction and Differential Scanning Calorimetry analysis revealed the presence of a molecular dispersion of drugs. These findings demonstrate the potential value of using ME as a fixed-dose combination technology for the delivery of EFV, FTC, and TDF.

ABSTRACT Microemulsions (MEs), which possess the properties of both high water‐dilutability (HWD) and on‐demand demulsification, might be more advantageous for their applications in actual technical fields. Hence, triethylamine laurate was utilized as the surfactant to construct HWD pH‐responsive MEs (C 12 TEA‐MEs) by means of the phase diagram. The structural features of C 12 TEA‐MEs were respectively characterized through conductivity, dynamic light scattering, and cryogenic transmission electron microscopy. Upon acidification with HCl, the monophasic MEs are rapidly and efficiently demulsified into oil–water phase separation regardless of the type of MEs. The C 12 TEA‐MEs can be diluted to a possible water mass fraction as high as 99.2%. The C 12 TEA‐MEs possess an excellent solubilization capacity for benzo[g,h,i]perylene (BghiP) from topsoils. The removal rate of BghiP can be up to 99.8%, even when the mass fraction of surfactant in C 12 TEA‐ME is diluted to 0.3%. More than 99.8% of the total BghiP in eluent enters the oil phase after demulsification, and the minimum mass ratio of the BghiP‐containing oil phase to the eluent can reach ∼1.0%. Meanwhile, the chemical oxygen demand of the water phase can be remarkably reduced to ~9.7 mgO 2 L −1 after a simple and conventional treatment, resulting in the treated water phase containing minimal organic species.

Formulation and heat stability of self-assembled O/W food-grade microemulsions formulated with bile salts or tween 80 as surfactants.