Search Results (206)

Background/Objectives: Otomycosis is a recurrent fungal infection of the external auditory canal. This disease is difficult to manage with current antifungal agents due to irritation, ototoxicity risk, and emerging resistance. Natural essential oils have been proposed as alternatives, yet their clinical application in otic formulations remains limited due to their poor solubility and stability. In this study, we report the first ear-drop formulation combining microemulsified Ocimum gratissimum essential oil and acetic acid for otomycosis treatment. Methods: The essential oil was quality-validated with eugenol content superior to 60%. A systematic formulation study was performed, and the Tween 20/isopropanol (4:1, w/w) mixture was selected as the optimal surfactant system, yielding a stable microemulsion with high encapsulation efficiency (~98%) and relevant physicochemical stability (up to 28 days). The final formulation containing 1% acetic acid and 0.3% micro-emulsified essential oil met pharmacopeial requirements in terms of appearance, pH, viscosity, and microbial limits. Results: Importantly, this micro-emulsified eardrop demonstrated significantly greater in vitro antifungal activity than 3% boric acid and 2% acetic acid eardrops in twelve clinical fungal isolates from Vietnamese swimmers, especially on Curvularia, Cunninghamella, Aspergillus terreus, and Bipolaris. Although less pronounced than 1% clotrimazole, the finalized formulation demonstrates better antifungal kinetics and a broader activity spectrum. Conclusions: This work provides relevant experimental evidence on the use of Ocimum gratissimum essential oil in a microemulsion delivery system and demonstrates its efficacy against clinically relevant otomycosis pathogens. The results establish a foundation for future in vivo and clinical studies. 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

Pomegranate peel, an abundant agro-industrial by-product, represents a sustainable source of bioactive polyphenols, particularly punicalagin, which has been associated with antioxidant and photoprotective potential. This study aimed to develop microemulsions (MEs) containing pomegranate peel extract for dermal delivery of punicalagin using biocompatible surfactant systems. Three MEs differing in surfactant–cosurfactant composition (ME-A, ME-P, and ME-E) were prepared. Each formulation solubilized 1% (w/w) of pomegranate peel extract and was evaluated regarding in vitro release behavior, skin permeation/retention, antioxidant activity, and in vitro sun protection factor (SPF). All investigated MEs provided sustained release of punicalagin (≈10–17% of the applied dose in 8 h). ME-A, based on an alkyl polyglucoside surfactant, showed a significantly higher cumulative release of punicalagin (60.4 µg/cm²) compared with ME-E and ME-P. In skin penetration/permeation studies, ME-A also exhibited the highest numerical total delivery of punicalagin (≈48.2 µg/cm² after 24 h), although differences among formulations were not statistically significant. All formulations demonstrated high antioxidant activity in the DPPH assay and measurable in vitro photoprotective potential, with SPF values ranging from approximately 11 to 14. Overall, pomegranate peel extract-loaded MEs showed potential as dermal delivery systems capable of improving solubilization and modulating skin delivery of punicalagin. The combination of agro-waste-derived bioactives with biocompatible surfactants highlights the potential of these systems as sustainable approaches for skincare formulations. Full article

An eco-friendly microemulsion biofungicide derived from Allamanda cathartica was developed for the control of papaya anthracnose caused by Colletotrichum gloeosporioides. The formulation was prepared by blending surfactants, carrier oil, and water and optimized using ternary phase diagrams to identify stable microemulsion systems. All selected formulations exhibited surface tension values ranging from 29 to 31 mN/m, while particle sizes ranged from 51.79 to 1801.05 nm. The optimized formulation, coded as AM8, consisted of 35% Allamanda concentrated liquid crude extract (ACLCE), 26% water, 13% alkyl polyglucoside surfactant, and 26% dimethylamide oil. Papaya fruits coated with the formulations showed significant reductions (p < 0.05) in anthracnose incidence caused by C. gloeosporioides. Control fruits treated with water showed 75% disease incidence, whereas fruits treated with benomyl showed 42% disease incidence. Disease incidence, severity, and disease index decreased with increasing formulation concentration, and fruits treated with the eight formulations at 10% concentration exhibited significantly lower disease incidence (0–17%) and disease index (0–17%), with disease severity consistently scored as zero. The Allamanda formulation demonstrated strong antifungal activity with EC₅₀ and EC₉₅ values of 1.839 and 7.067 mg/mL (w/v), respectively, at the 95% confidence level. The optimized formulation AM8 remained stable for up to one year and showed superior disease control performance compared with the conventional fungicide benomyl. In addition, the formulation maintained fruit quality by preserving firmness, peel color, and soluble solids concentration, thereby extending papaya shelf life up to 30 days without adversely affecting the natural ripening process. These findings demonstrate the potential of Allamanda-based microemulsion formulations as sustainable biofungicides for postharvest control of papaya anthracnose and provide a promising alternative to conventional synthetic fungicides. 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

Ozone layer depletion exacerbates UV-induced skin damage, including oxidative stress and DNA lesions, thereby increasing the risk of photoaging and malignant transformation. Natural extracts have gained increasing attention as a photoprotective ingredient in cosmeceutical products. Kaempferia galanga, a species in the Zingiberaceae family traditionally used for skin-related treatment and listed in the CosIng database, exhibits multiple biologically relevant properties; however, its anti-photoaging and anti-photo-senescence effects in human dermal fibroblasts remain unexplored. This study investigated the in vitro photoprotective effects of K. galanga extract against UVB-induced photoaging and cellular senescence in human dermal fibroblasts. The ethanolic extract of K. galanga rhizomes (EKGRs) contained ethyl p-methoxycinnamate (EPMC) as a major constituent (33.7 ± 3.7% (w/w) of the crude extract), identified by HPLC-UV. Additionally, EKGR exhibited significant protective effects in UVB-irradiated fibroblasts. EKGR showed no cytotoxicity at concentrations up to 50.0 µg/mL, as determined by the MTT assay. EKGR pretreatment significantly reduced UVB-induced cellular senescence in human dermal fibroblasts compared with UVB-exposed cells (22.2 ± 2.7% vs. 36.7 ± 8.0%). Furthermore, pretreatment with EKGR prior to UVB exposure resulted in a significant increase in pro-collagen type I production (37,075.1 ± 7532.2 pg/mL) and a concomitant decrease in MMP-1 secretion (25,754.1 ± 4042.0 pg/mL) relative to UVB-exposed cells (26,845.8 ± 1454.6 and 39,910.8 ± 6035.1 pg/mL, respectively). To demonstrate formulation feasibility, EKGR was incorporated into an oil-in-water microemulsion, which exhibited concentration-dependent SPF enhancement. Collectively, these findings demonstrate the photoprotective efficacy of EPMC-rich EKGR and highlight its potential as a cosmeceutical ingredient for mitigating UVB-induced photo-senescence and skin aging, with an additional SPF boosting effect. To our knowledge, this study provides the first evidence of EKGR-mediated protection against UVB-induced cellular senescence in human dermal fibroblasts. Full article

This study investigates the key performance-related fuel properties of emulsifier–diesel solutions and ethanol-in-diesel microemulsions. This work begins with the in situ polymerization of long alkyl chain-substituted glycidyl methacrylate (R-GMA) in diesel and the optional presence of a second methacrylate monomer. The resulting diesel-soluble oligomer functions as a nonionic emulsifier. Controlled amounts of ethanol are subsequently incorporated into the emulsifier–diesel solution to form a stable microemulsion, referred to as E-Diesel. This study examines how the structure of the emulsifier influences key fuel properties, including (i) ethanol–diesel miscibility, (ii) gross calorific value, (iii) Ramsbottom carbon residue (% of fuel), (iv) entrapped polycyclic aromatic hydrocarbons (PAHs), and (v) fuel lubricity. Both the hydrophilic–hydrophobic balance and the structure of the emulsifier side chains are found to significantly affect these properties. Compared with neat diesel, oligomeric emulsifiers enable the substantial dispersion of ethanol in diesel (up to 18 wt.%). The resulting fuel exhibits a gross calorific value exceeding the theoretical sum of diesel and ethanol at the same composition (a synergistic effect) and achieves an enhancement in lubricity up to 49.5% relative to neat diesel at a 5% emulsifier loading. Although the presence of emulsifiers leads to an increase in the carbon residue by up to 54.7% compared to neat diesel during controlled pyrolysis, it simultaneously reduces the PAH content in the exhaust. Overall, this study establishes fundamental correlations among microemulsion stability, combustion synergy, carbon residue formulation, and fuel lubricity, which are governed by the structure of the emulsifier. Full article

Mesoporous bioactive glass nanoparticles (MBGNs) are promising for bone tissue engineering; however, surgical site infection and oxidative stress often compromise regeneration. To address this, MBGNs co-doped with cerium (Ce), zinc (Zn), and strontium (Sr) were synthesized using a microemulsion-assisted sol-gel route (xCe-yZn-Sr-MBGNs; x = 0, 1, 2; y = 0, 0.5, 1). The resulting spherical nanoparticles (150–200 nm) exhibited a mesoporous structure with a specific surface area of (~340–425 m²/g), sustained ion release, and apatite formation in simulated body fluid. In vitro evaluations with MC3T3-E1 pre-osteoblasts demonstrated dose-dependent cytocompatibility, specifically in the co-doped formulations; however, higher Ce concentrations (2Ce-yZn-Sr-MBGNs) reduced viability following prolonged exposure. Crucially, the 1Ce-1Zn-Sr-MBGNs significantly enhanced osteogenic differentiation, as evidenced by a two-fold increase in osteogenic marker gene expression and a ~45% increase in calcium mineral deposition compared to undoped MBGNs within 14 days. Moreover, these particles accelerated cell migration, achieving ~70% scratch-wound closure within 24 h. Furthermore, 1Ce-1Zn-Sr-MBGNs displayed strong radical scavenging capacity and potent antibacterial activity against S. aureus and P. aeruginosa. These findings indicated that 1Ce-1Zn-Sr-MBGNs exhibited multiple therapeutic effects, including antibacterial, radical-scavenging, and osteogenic effects. By optimizing dopant ratios, these multifunctional nanomaterials emerge as promising candidates for next-generation bone grafts or implant coatings. Within the scope of this study, they demonstrated the capacity to simultaneously address three critical challenges in bone healing: controlling infection, mitigating oxidative stress, and promoting mineralized tissue formation. While these in vitro results provide a robust foundation, further in vivo validation is warranted to confirm their efficacy within complex physiological environments. 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

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. Full article

Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus, is driven by a tri-component system involving the pinewood nematode, Monochamus spp. beetle vectors, and susceptible pine hosts. Chemical control remains a scenario-dependent option for emergency suppression and high-value protection, but its deployment is constrained by strong regional regulatory and practical differences. In Europe (e.g., Portugal and Spain), field chemical control is generally not practiced; post-harvest phytosanitary treatments for wood and wood packaging rely mainly on heat treatment, and among ISPMs only sulfuryl fluoride is listed for wood treatment with limited use. This review focuses on recent progress in PWD chemical control, summarizing advances in nematicide discovery and modes of action, greener formulations and delivery technologies, and evidence-based, scenario-oriented applications (standing-tree protection, vector suppression, and infested-wood/inoculum management). Recent studies highlight accelerated development of target-oriented nematicides acting on key pathways such as neural transmission and mitochondrial energy metabolism, with structure–activity relationship (SAR) efforts enabling lead optimization. Formulation innovations (water-based and low-solvent products, microemulsions and suspensions) improve stability and operational safety, while controlled-release delivery systems (e.g., micro/nanocapsules) enhance penetration and persistence. Application technologies such as trunk injection, aerial/Unmanned aerial vehicle (UAV) operations, and fumigation/treatment approaches further strengthen scenario compatibility and operational efficiency. Future research should prioritize robust target–mechanism evidence, resistance risk management and rotation strategies, greener formulations with smart delivery, and scenario-based exposure and compliance evaluation to support precise, green, and sustainable integrated control together with biological and other sustainable approaches. Full article

Injecting chemical agents into tree trunks is a key method for preventing pine wilt disease (PWD). However, the long-term use of conventional trunk injection agents such as emamectin benzoate (EB) and avermectin (AVM) may lead to nematode resistance. Therefore, it is crucial to evaluate the potential of new-generation nematicides, including fluopyram (FLU) and its compound formulations, as alternatives to EB and AVM in PWD prevention. In this study, four trunk injection agents, i.e., 5% FLU microemulsion (ME), 2% AVM + 6% FLU ME, 5% EB ME, and 5% AVM emulsifiable concentrate (EC), were injected into Pinus massoniana trunks, and their residual dynamics over time and preventive effects on PWD were compared. Results showed that all agents were transported to various parts of the trees within 90 days post-injection, with FLU showing significantly stronger translocation compared with EB and AVM. At 660 days post-injection, the active ingredient levels of 5% FLU ME in apical branches remained significantly higher than those of the other three agents at both tested doses (30 and 60 mL). Artificial inoculation with 10,000 Bursaphelenchus xylophilus nematodes per tree at 90 days post-injection showed that trees injected with 5% FLU ME and 2% AVM + 6% FLU ME had nearly 100% disease prevention rates at both doses, outperforming 5% EB ME and 5% AVM EC. A second nematode inoculation at 480 days post-injection showed that 2% AVM + 6% FLU ME showed 50% efficacy, outperforming 5% EB ME (25% efficacy). These findings offer a foundation for developing alternative trunk injection strategies for future PWD management in China. Full article

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. Full article

Ophthalmic drug delivery encounters unique challenges due to the anatomical and physiological ocular barriers, necessitating the development of novel drug delivery systems (NDDSs). This review focuses on emerging therapeutic platforms, including nanoemulsions (NEs), microemulsions (MEs), self-emulsifying drug delivery systems (SEDDSs) such as self-nano emulsifying drug delivery systems (SNEDDSs) and self-micro emulsifying drug delivery systems (SMEDDSs), emulgels, and in situ-forming emulgels, as novel strategies for enhancing ocular drug delivery. NEs and MEs, due to their small globule size, excellent drug solubility, stability, and bioavailability, offer promising solutions for effective ocular therapy. SEDDSs further enhance the stability and bioavailability of hydrophobic drugs through self-emulsification in aqueous environments. Emulgels, combining the benefits of emulsions and gels, provide sustained and controlled release of therapeutic agents, improving the ocular retention time and therapeutic efficacy. Additionally, in situ-forming emulgels offer the advantage of liquid-to-gel transition upon contact with ocular surfaces, optimizing drug delivery. The review discusses various ocular diseases, challenges for ocular delivery of conventional formulations, updates on emulsion-based novel drug delivery systems for ophthalmic drug delivery, mechanisms of enhanced ocular permeation, formulation strategies, advantages, and challenges, design-of-experiment considerations for optimization, characterizations, and recent advancements in these systems including patents and clinical trials, highlighting their potential for improving the treatment of various ocular diseases. Furthermore, this review explores marketed ophthalmic emulsions and future prospects for integrating these NDDSs into clinical ophthalmology, emphasizing their ability to overcome ocular barriers and enhance therapeutic efficacy. Full article