Search Results (90)

Background: Solar ultraviolet (UV) radiation is a major contributor to skin damage, driving the demand for safer and more sustainable photoprotective systems. Mycosporine-like amino acids (MAAs) have emerged as promising natural UV filters due to their strong absorption and photostability; however, their application is limited by poor chemical stability in aqueous environments. Objective: The present study aimed to develop and optimize a nanoemulsion-based lip balm incorporating a MAAs-rich extract from Catenella sp., addressing stability limitations while enhancing photoprotective performance. Methods: A MAAs-rich extract was obtained and characterized by UHPLC-DAD, followed by cytotoxicity evaluation in NIH-3T3 fibroblasts and stability assessment under stress conditions. A water-in-oil (w/o) nanoemulsion was rationally developed using pseudo-ternary phase diagrams and optimized through a Box–Behnken experimental design, considering aqueous phase, surfactant mixture, and sonication time as key variables. The optimized nanoemulsion was subsequently incorporated into a lip balm matrix, which was formulated and optimized using a mixture design approach to evaluate thermal, mechanical, and sensory properties. Results: The extract exhibited a high MAAs content (9.53 mg g⁻¹ DW) and low cytotoxicity (IC₅₀ > 100 µg/mL), but pronounced hydrolytic instability, particularly under alkaline conditions, while remaining photostable. The optimized nanoemulsion achieved a droplet size below 200 nm and low polydispersity (PDI < 0.3). Importantly, incorporation of MAAs into nanoemulsion significantly enhanced the in vitro sun protection factor (SPF), increasing from 16.1 (extract) to 35.4, while maintaining broad-spectrum UV coverage (λc = 380 nm). The blank nanoemulsion also contributed to UV attenuation, indicating a synergistic effect of the colloidal system. The optimized lip balm formulation (33% beeswax, 40% nanoemulsion, 22% shea butter, 1% candelilla wax, 4% carnauba wax) demonstrated suitable melting behavior, mechanical resistance, and high sensory acceptance. Conclusions: This study demonstrates that nanoemulsion-based structuring combined with statistical formulation design provides an effective strategy to stabilize MAAs and enhance their photoprotective efficacy, supporting the development of high-performance, natural sunscreen products. Full article

Octacosanol (OCT) is a natural bioactive compound with multiple physiological activities. However, its poor aqueous solubility limits its application in functional beverages, and existing delivery systems suffer from low loading and excessive emulsifier use. This study aimed to develop a food-grade OCT-loaded microemulsion (OCT-ME) with high loading capacity. The formulation was optimized via pseudo-ternary phase diagram analysis combined with particle size and polydispersity index (PDI) measurements, and the characterization and biocompatibility of the optimized OCT-ME were systematically evaluated. The optimal formulation (w/w) consisted of 2.4% corn oil, 16.2% mixed emulsifiers (Tween 80/Span 80, HLB = 13), 5.4% 1,2-propanediol (Km = 3:1), and 75.0% deionized water, achieving a high OCT loading capacity of 1.0% (w/w). The resulting OCT-ME displayed a uniform particle size of 10.37 nm with a low PDI and exhibited excellent stability, favorable gastric OCT protection, and superior biocompatibility (cell viability > 90% at 5–25 μg/mL). This work addresses the key limitations of existing OCT delivery systems, providing theoretical support for the efficient solubilization and delivery of OCT in functional beverages. Full article

Objective: This study aimed to develop an oral celastrol-loaded self-microemulsifying drug delivery system (Cel-SMEDDS) to enhance the therapeutic efficacy against rheumatoid arthritis and reduce toxicity. Methods: The optimal Cel-SMEDDS formulation, identified through solubility screening, excipient compatibility assays, and pseudo-ternary phase diagram analysis, was characterized by particle size, PDI, zeta potential, in vitro release, and stability. In vitro anti-inflammatory activity was evaluated in LPS-induced RAW264.7 macrophages, while in vivo anti-RA efficacy was assessed in CIA mice via paw swelling, clinical scoring, serum TNF-α, and joint histopathology. Preliminary safety was examined by hematological, serum biochemical, and histopathological analyses in mice. Results: The optimal Cel-SMEDDS formulation consisted of LABRAFIL M 1944 CS-Kolliphor RH40-CAPRYOL 90 (0.2:0.48:0.32, w/w/w) with a drug loading of 1.5% (w/w). It spontaneously formed uniform microemulsions with a mean particle size of 26.70 nm, PDI of 0.067, and zeta potential of −2.87 mV. In vitro, Cel-SMEDDS showed enhanced cytotoxicity against M1-type macrophages (IC₅₀ = 0.1753 μg/mL vs. 0.2684 μg/mL for free Cel), significantly suppressed pro-inflammatory TNF-α and IL-1β expression, and upregulated anti-inflammatory IL-10. In CIA mice, oral Cel-SMEDDS reduced paw swelling by 37.42% (vs. 22.79% for free Cel), markedly decreased serum and intra-articular TNF-α levels, and alleviated articular cartilage damage. Preliminary safety evaluation demonstrated no significant abnormalities in hematological parameters, liver/kidney function, or major organ histology. Conclusions: The optimized oral Cel-SMEDDS effectively inhibits the expression of pro-inflammatory cytokine TNF-α both in vitro and in vivo, exhibits superior anti-RA activity compared to free Cel, and possesses favorable safety. This formulation addresses the key limitations of celastrol and shows promising potential for clinical translation in RA treatment. Full article

Clove essential oils (CEOs) are widely studied because of their biological potential; however, their applications are limited because of their water immiscibility. Microemulsions (MEs) can protect, deliver, and enhance the biological activities of CEOs, including their antioxidant and cytotoxic activities. In this research, the effects of ethanol as a cosurfactant and the polysorbate 80:cosurfactant mixture (S_mix = 1:0, 9:1, 7:1, 5:1, 3:1, and 1:1) on the formation of CEO-MEs were evaluated via a pseudo-ternary phase diagram. After 35 days, all the systems produced clear, monodisperse, and thermodynamically stable MEs, characterized by average sizes below 25.6 nm and low polydispersity index values (<0.21). The S_mix dose–response experiments without CEO revealed that the S_mix ratios of 1:1 and 3:1 resulted in the lowest cytotoxicity to HT-29 (colorectal adenocarcinoma) cells. The antioxidant capacity of the CEO-ME was greater than that of the CEO. Finally, the CEO-MEs enhanced the in vitro cytotoxic activity of the CEO against Caco-2, HT-29, HeLa, PC-3, and A549 cancer cells. These findings provide valuable information for the development of low-energy clove essential oil MEs for potential incorporation into functional foods and pharmaceutical products. Full article

The development of stable and efficient essential oil delivery systems remains a persistent challenge in active food packaging applications. This research aimed to develop a multi-functional soy protein isolate (SPI)-based composite gel film integrating a tea tree oil micro emulsion (TME) via a microemulsion-in-gel approach, featuring sustained antioxidant release. The TME was first optimized using pseudo-ternary phase diagrams and exhibited excellent physicochemical stability. It maintained a droplet size ranging from 10 to 13 nm, with a polydispersity index (PDI) less than 0.2 under diverse stress situations (such as dilution, heat treatment, pH change, centrifugation, and 30-day storage). Afterward, TME-SPI composite gel films containing 1 to 3% TME were fabricated through solution casting and subsequent gelation of the protein matrix. The incorporation of TME markedly improved the properties of the gel film network. It raised the opacity by around 2.5 times, boosted the elongation at break to 144% (which is three times that of the control), and distinctively enhanced both water solubility and the water vapor barrier. Importantly, the 2% TME-SPI gel film exhibited sustained antioxidant activity from within the gel matrix, retaining more than 50% of its original 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity after 72 h, significantly outperforming films containing free TTO. The microemulsion-in-gel approach was shown to be effective in creating SPI-based gel films that possess combined light-barrier characteristics, adjustable moisture resistance, improved flexibility, and extended antioxidant release. This offers a promising framework for the next generation of active food packaging. Furthermore, the composite gel films exhibited concentration-dependent antibacterial activity against Staphylococcus aureus, with the 3% TME-SPI film achieving an 82% inhibition rate, thus experimentally validating its active packaging potential. Full article

Kamala is a traditional Thai herbal knee poultice containing phenylbutenoid compounds with potent anti-inflammatory activity; however, its conventional form is inconvenient to use and exhibits variability in active compound content. This study aimed to develop a Kamala-based nanoemulsion gel to enhance dermal delivery and improve formulation consistency. Oils, surfactants, and co-surfactants were screened for their solubilization efficiency of (E)-1-(3,4-dimethoxyphenyl)butadiene (DMPBD) and (E)-4-(3′,4′-dimethoxyphenyl)but-3-en-1-ol (Compound D) using GC–MS. Pseudo-ternary phase diagrams were constructed to identify isotropic regions, and nanoemulsions with different Smix ratios were prepared by ultrasonication. Droplet size, polydispersity index (PDI), and short-term stability were evaluated. The optimized nanoemulsion was incorporated into a gel, and in vitro release was assessed using Franz diffusion cells. Coconut oil exhibited the highest solubilization capacity for both markers. A Tween 80:n-butanol system (2:1) generated the largest isotropic region (22.88%). The optimized formulation (Kamala extract:coconut oil:Smix:water = 1:2:50:47) showed droplet sizes of 77.92 ± 8.34 nm at 0 h and 130.89 ± 29.16 nm at 72 h, with PDI < 0.20. The nanoemulsion gel prepared with Aristoflex Velvet^® (1% w/w) was transparent and physically stable. Franz diffusion studies demonstrated enhanced cumulative release and flux of Compound D in PBS containing 1% Tween 80. These findings indicate that the Kamala nanoemulsion gel is a promising topical delivery system for phenylbutenoid compounds in knee osteoarthritis. Full article

The search for harmless alternative solutions to protect crops has become urgent and has recently attracted widespread attention from researchers around the world focusing on natural polyphenols, which represent a treasure chest of molecules with potent activities. Due to the low water solubility of polyphenols, microemulsions were selected as nanovectors. Curcumin and mangiferin solubility in different excipients was evaluated by HPLC. Microemulsion was developed using pseudo-ternary phase diagrams. Sizes and polydispersity of microemulsion globules were evaluated by dynamic light scattering. Activity against Fusarium verticillioides was evaluated by a microdilution method. Vitamin E acetate was selected as the oily phase, Transcutol P as cosurfactant and Tween 80 as surfactant. S_mix was composed of Transcutol P and Tween 80 in a 1:2 gravimetric ratio and combined with oil-phase vitamin E acetate at a weight ratio of 3:1. Microemulsions were loaded with 5 mg/mL of each polyphenol and recovery results were 99.5% and 99.3% for curcumin and mangiferin, respectively. Sizes of the lipid phase were 121.7 ± 29.2 nm and 172.6 ± 19.3 nm, respectively, for mangiferin and curcumin microemulsions. F. verticillioides was very susceptible to both microemulsions with a very high activity at a dose of 0.9 mg/mL (log-4 reduction), evidencing a possible use of these nanoformulations to protect crops from F. verticillioides. Full article

This study developed a microemulsion system based on diatomaceous earth (DE) for the topical delivery of resveratrol. The microemulsions were prepared using pseudo-ternary phase diagrams. A 4:1 ethanol:virgin coconut oil ratio resulted in a larger microemulsion region than a 3:1 ratio. Two formulations with oil (ethanol:virgin coconut oil, 3:1):Cremophor RH40:water ratios of 1:5:4 (ME1) and 2:5:3 (ME2) were selected for resveratrol loading and subsequently combined with DE at ratios of DE:microemulsion (DE:ME) 0.5:1, 0.5:2, and 0.5:3. The transmission electron microscopy images demonstrated the different microstructures of the microemulsions. Rheological analysis revealed an increase in storage modulus and a decrease in the linear viscoelastic region with increasing DE concentration, particularly in ME1. Differential scanning calorimetry showed disruption of boundary water following DE incorporation. Fourier-transform infrared spectroscopy indicated primarily physical interactions between resveratrol and the DE:ME system. DE:ME demonstrated high resveratrol content, approaching 100%. DE:ME1 0.5:2 significantly enhanced resveratrol permeation, resulting in a 3-fold increase compared with the microemulsion alone after 8 h. DE:ME1 0.5:2 and DE:ME2 0.5:3 enhanced the photostability of resveratrol and the formulations remained stable after storage at 40 °C for 6 months. The DE:ME system maintained its cellular uptake capability, preserved the biological activity of resveratrol, and exhibited low cytotoxicity in human keratinocytes, with cell viability remaining above 70%. These results highlight the potential of DE-based systems for incorporating microemulsions of low-water soluble photo-sensitizing substances in topical drug delivery applications. Full article

This study presents a promising strategy for the fabrication of a novel chitosan-based nanogel-in-oil system by integrating the development of a water-in-oil (W/O) microemulsion containing chitosan as a template, followed by crosslinking with genipin, a natural crosslinking agent, via emulsion crosslinking. To develop the W/O microemulsion template, nanometer-sized internal aqueous droplets were successfully formed in cottonseed oil, a vegetable oil, using a blend of nonionic surfactants, polysorbate 80 and sorbitan monooleate. A pseudoternary phase diagram was constructed to investigate the phase behavior of systems composed of chitosan solution, mixed surfactant, and cottonseed oil. Compositions falling within the monophasic region were selected for further formulation optimization. The microemulsions were characterized for droplet size, size distribution, electrical conductivity, and viscosity. The optimal microemulsion exhibited W/O characteristics with the lowest viscosity. Dynamic light scattering (DLS) analysis confirmed the presence of uniformly distributed nanometer-sized droplets, as evidenced by a Z-average diameter of 92.9 ± 2.3 nm and a PDI of 0.100 ± 0.072. The microemulsion system demonstrated physical stability, as confirmed by centrifugal testing. Crosslinking of chitosan with genipin was monitored by fluorescence intensity measurements of the crosslinking products. Fourier transform infrared spectroscopy further confirmed the formation of genipin-crosslinked chitosan structure. DLS and transmission electron microscopy revealed that the nanogels possessed nanoscale dimensions and discrete spherical morphologies. Overall, this approach demonstrates a viable route for producing a nanogel-in-oil system by combining microemulsion templating with emulsion crosslinking. Full article

Background/Objectives: Topical treatment of cutaneous tuberculosis (CTB) requires reliable models to evaluate dermal drug release and diffusion, particularly for fixed-dose combinations (FDCs) with contrasting physicochemical properties. Human skin remains the reference standard but poses ethical, logistical, and reproducibility challenges. This study investigated the suitability of Strat-M^® synthetic membranes as an alternative to human skin for assessing the simultaneous release and diffusion of clofazimine (CFZ) and pyrazinamide (PZA) from a topical FDC, and aimed to develop an optimized dermal emulsion using a Quality-by-Design (QbD)-informed formulation development tool. Methods: Self-emulsifying dermal emulsions containing CFZ and PZA were developed following QbD principles. Preformulation studies included drug solubility screening, oil phase selection, and pseudoternary phase diagram construction to identify stable emulsion regions. Formulations were characterized for droplet size, polydispersity index, zeta potential, viscosity, self-emulsification efficiency, and thermodynamic stability. Eight stable emulsions were identified, of which four were selected for in vitro drug release studies. The peppermint oil-based emulsion (PPO415) was further evaluated in comparative diffusion studies using Strat-M^® membranes and ex vivo human skin (Caucasian and African). Results: PPO415 demonstrated favorable physicochemical properties, including high CFZ solubility, uniform droplet distribution, and suitability for dermal application. Comparative diffusion studies showed that Strat-M^® underestimated the partitioning of lipophilic CFZ while overestimating the diffusion of hydrophilic PZA relative to human skin. These differences were attributed to compositional and structural disparities between synthetic membranes and biological skin. Conclusions: Strat-M^® membranes show potential as a reproducible and ethical in vitro screening tool during early-stage formulation development for topical FDCs. However, ex vivo human skin remains essential for accurately predicting dermal drug distribution and therapeutic performance. Full article

In this work, the characteristic temperatures (solidus and liquidus) of selected lead blast furnace slags were investigated using in situ high-temperature optical microscopy. The effects of the basicity of the slag (CaO/SiO₂), the Fe/SiO₂ ratio, and the Zn content were investigated. The deformation temperature associated with the rounding of the sample edges and the temperature at which 75% of the sample height decreases were experimentally considered as the solidus and liquidus temperatures, respectively. The pseudoternary phase diagrams CaO-SiO₂-Fe_0.63Zn_0.37O and FeO-Ca_0.54Si_0.46O_1.46-ZnO were calculated, along with the crystallization curves, using the thermodynamic software FactSage to estimate the characteristic temperatures and phase evolution during the cooling of the slag. The difference between the calculated and experimental solidus and liquidus temperatures was about 70 °C. The results of XRD, SEM, and DSC analysis at high temperatures showed that spinel (ZnFe₂O₄), melilite (Ca₂ZnSi₂O₇), and andradite (Ca₃Fe₂Si₃O₁₂) were the base crystals for all slag samples. The liquidus temperature increases with decreasing slag basicity (CaO/SiO₂), while the liquidus temperature increases with increasing Fe/SiO₂ ratio or Zn content. Full article

Background/Objectives: According to the WHO, more than one million deaths of liver cancer patients will occur in 2030. Hepatocellular carcinoma (HCC) is the third leading cause of death among all cancer types. Doxorubicin is commonly used for the treatment of HCC, yet it possesses major side effects. The aim of this work was to formulate a nanoemulsion of Peltophorum pterocarpum extract containing bergenin intended for intravenous injection as a natural alternative to doxorubicin. Methods: The saturation solubility of the extract in different oils, surfactants, and co-surfactants was determined. Surfactant to co-surfactant mixtures (Smix) were used at six different weight ratios. A pseudoternary phase diagram was constructed, and the ratio with the highest area was chosen. Six formulations were prepared by changing the oil-to-Smix ratio. They were evaluated by percentage transmission, dilution test, self-emulsification, pH, viscosity, drug content, droplet size, PDI, zeta potential, TEM, in vitro drug release, stability, in vitro hemolysis percentage, and cytotoxicity (for the optimized formula). Results: F6 of oil-to-Smix ratio (1:6) was chosen for further investigations, as it possesses the lowest droplet size, the highest zeta potential, drug content, and in vitro drug release. The pH, viscosity, and self-emulsification time of F6 were also acceptable. F6 possesses shelf-life stability and is hemocompatible. It possesses high cytotoxicity against the HepG-2 cell line (IC₅₀ = 14.19 µg/mL). Conclusions: Although the nanoemulsion is less potent than doxorubicin in terms of IC₅₀, it offers a safer profile and natural origin, which may be used for the treatment of HCC. Full article

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 (S_mix-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 S_mix 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. Full article

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, S_mix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article

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. Full article