Search Results (77)

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

The extensive use of submicron emulsion systems, particularly those stabilized by nonionic surfactants, with their proven effectiveness and safety profile, provides a reassuring foundation for our research. Consequently, we designed and engineered new submicron emulsion formulations stabilized with a biocompatible surfactant polyoxyethylated cocoamine, whose nonionic character is due to a high degree of polyoxyethylation. We chose oleic acid as the oil phase, a fatty acid known for its beneficial properties. This led to novel biocompatible nanoemulsions with high stability and cosurfactant-free microemulsions. The dynamic light scattering studies confirmed that both formulations have a nanometric size and low polydispersity index values. Moreover, transmission electron microscopy verified the nanodroplets’ morphological homogeneity and spherical shape. The resulting nanoplatforms can be applied to carry bioactive agents in the pharmaceutical and cosmetic fields. For this reason, we solubilized newly synthesized 5-dimethylamino-5′-nitro-2,2′-bithiophene as a model hydrophobic cargo for delivering poorly water-soluble compounds. This dye was chosen due to its strong solvatochromic behavior and suitability for micropolarity analysis via UV–Vis spectroscopy. We also present a simple method for rapid micropolarity screening to assess the type of nanodispersion via solvatochromic shift as an alternative procedure for evaluating of the oils used to fabricate nanoformulations for pharmaceutical and cosmetic purposes. Full article

Polymer network-based nanogels (NGs) and microgels (MGs) have emerged as highly versatile platforms for advanced drug delivery, owing to their tunable architecture, biocompatibility, and responsiveness to diverse stimuli. This review presents a comprehensive and structured analysis of NG/MGs, encompassing their classification based on polymer origin, crosslinking mechanisms, composition, charge, stimuli-responsiveness, and structural architecture. We detail synthesis strategies—including inverse microemulsion and radiation-induced polymerization—and highlight key characterization techniques essential for evaluating physicochemical and functional properties. Emphasis is placed on the design-driven applications of NG/MGs in overcoming biological barriers and enabling targeted therapies, particularly in cancer, inflammation, diabetes, and viral infections. Multifunctional NGs integrating therapeutic and diagnostic capabilities (theranostics), as well as emerging platforms for immunotherapy and personalized medicine, are critically discussed. Finally, we address translational challenges and future directions, including scalable manufacturing, regulatory considerations, and integration with smart diagnostics. This review aims to serve as a foundational resource for researchers and clinicians developing next-generation NG/MG-based therapeutics. Full article

Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of lipid metabolism, making its agonists valuable therapeutic targets for various diseases, including chronic peripheral neuropathy. Existing PPARα agonists face limitations such as poor selectivity, sub-optimal bioavailability, and safety concerns. We previously demonstrated that A190, a novel, potent, and selective PPARα agonist, effectively alleviates chemotherapy-induced peripheral neuropathy and CFA-induced inflammatory pain as a non-opioid therapeutic agent. However, A190 alone has solubility and permeability issues that limits its oral delivery. To overcome this challenge, in this study, four new-generation ester prodrugs of A190; A190-PD-9 (methyl ester), A190-PD-14 (ethyl ester), A190-PD-154 (isopropyl ester), and A190-PD-60 (cyclic carbonate) were synthesized and evaluated for their enzymatic bioconversion and chemical stability. The lead candidate, A190-PD-60, was further formulated as a microemulsion (A190-PD-60-ME) and optimized via Box–Behnken design. A190-PD-60-ME featured nano-sized droplets (~120 nm), low polydispersity (PDI < 0.3), and high drug loading (>90%) with significant improvement in artificial membrane permeability. Crucially, pharmacokinetic evaluation in rats demonstrated that A190-PD-60-ME reached a 16.6-fold higher Cmax (439 ng/mL) and a 5.9-fold increase in relative oral bioavailability compared with an A190-PD-60 dispersion. These findings support the combined prodrug-microemulsion approach as a promising strategy to overcome oral bioavailability challenges and advance PPARα-targeted therapies. Full article

Background: Anthralin is known for its efficacy in treating psoriasis and acne, possessing poor solubility. Addressing these limitations, the present study endeavors to develop a microemulgel formulation of anthralin aimed at enhancing solubility. Method: The solubility study was performed in various solvents. An o/w (oil-in-water) emulsion was formed using the water titration method, which was optimized by statistical experimental design half-run CCD. The final optimized batch was evaluated for physicochemical and in vitro properties Result: The final optimized batch showed a particle size (PS) of 417 nm, −25.2 mV zeta potential (ZP) and pH 5.8, which remained stable upon centrifugation, heating–cooling and freeze–thawing cycle. Furthermore, microemulsion with Carbopol 943 5% w/v was selected as the gel base for the formation of microemulgel characterized by PS, ZP, pH, and viscosity of 230 nm, −50.6 mV, 6.9 and 14,200 cps, respectively, that ensured it a high enough stability. In silico molecular docking between ligand and protein provides the binding energies validating the interaction. Hence, the in silico study was performed for psoriasis and P. acne proteins. An in vitro antibacterial activity study on Propionibacterium revealed a significant efficiency of the formulation and MTT assay using L929 cell line in the presence of the drug-loaded microemulgel indicated an inhibition of growth proving that formulation has anti-psoriatic activity. Conclusions: Combination therapy with Clindamycin might improve efficacy while reducing antibiotic resistance risks. Full article

Semicrystalline polystyrene spheroidal nanoparticles (50–100 nm) were obtained via microemulsion polymerization. They were evaluated as coal collectors in a low-rank carbonaceous mineral containing 2% organic carbon. The recovery of coal using nanoparticles as collectors was 88.2%, in contrast to 53.2%, 46.4%, and 44.8% achieved using an amine-type compound, kerosene, and diesel, respectively. X-ray photoelectron spectroscopy (XPS) and zeta potential measurements confirmed the polystyrene–mineral surface chemical interaction. A Box–Behnken experimental design for flotation optimization was applied, and the results showed that the coal recovery increased up to 99.5% when the dosage of the collector was increased. A contact angle study and density functional theory calculations, together with XPS results, allowed us to postulate an interaction mechanism in which polystyrene nanoparticles adsorb onto the coal surface through hydrophobic interactions, rendering the oxidized surface hydrophobic and the coal buoyant by adhering to the gas bubbles. Full article

Background: Tuberculosis remains a significant global health issue, and the rise of drug-resistant strains is becoming increasingly concerning. Currently, treatment options are limited to systemic regimens; however, developing topical drug delivery systems could offer advantages for treating cutaneous tuberculosis (CTB) when applied directly to the lesions. We developed topical emulsions using the self-emulsification mechanism that combine fixed doses of isoniazid (INH) and rifampicin (RIF) using a quality-by-design approach. Methods: Preformulation studies pertaining to drug solubility in various solvents, the construction of pseudoternary diagrams to identify self-emulsification regions for each tested excipient combination, and the preparation of checkpoint formulations were conducted and visually examined. Formulations displaying no physical instabilities were subsequently exposed to characterization experiments, including droplet size determination, zeta potential, size distribution, viscosity, pH, self-emulsification, cloud point, robustness to dilution, and thermodynamic stability assessment. Three selected formulations were consequently subjected to membrane release experiments, followed by skin diffusion studies, and INH and RIF stability in these emulsions was determined, because these drugs have a known interaction. Conclusions: While incorporating essential oils in a topical formulation improved RIF solubility, it also resulted in several instabilities. RIF exhibited greater susceptibility to degradation under higher temperatures and lower pH conditions. However, drug release from all formulations tested was confirmed. Notably, olive oil microemulsions demonstrated the most favorable characteristics for dermal drug delivery; nonetheless, drug diffusion into and through the skin (which was not desired) could not be quantified. Despite these challenges, the findings indicate that topical drug delivery systems using the self-emulsification process can facilitate the direct treatment of CTB. Full article

The low efficacy of traditional single-component pesticide formulations has resulted in excessive pesticide application, the evolution of pest resistance, and a range of food safety and environmental concerns. Developing efficient composite nanopesticides represents a critical strategy for addressing the above challenges. In this study, solid nanodispersions (SNDs) co-loaded with prochloraz and azoxystrobin were constructed through a self-emulsifying carrier adsorption method. The antifungal activities of the composite SND with a 14:1 ratio of prochloraz to azoxystrobin against Fusarium graminearum and Pyricularia oryzae were 2.3-fold and 1.6-fold higher than those of commercial microemulsions (MEs) with the same proportion of active ingredients. The SND could cause severe oxidative damage to fungi, by reducing the activities of superoxide dismutase (SOD) and catalase (CAT), and break the permeability of cell membranes, resulting in fungal death. Additionally, the composite SND exhibited superior foliar wettability and biosafety with a minimal environmental cost, thereby enhancing the pesticide’s effective utilization rate. This research provides theoretical and technical support for the design and development of high-efficiency composite nano-fungicide, holding promise for sustainable disease management. Full article

Using microemulsions (µEs) as preservation media for cells was pursued in the 1990s; however, the difficulty in formulating biocompatible µEs and keeping unacclimatized cells alive for more than three days hindered developments in this area. This work explores the use of fully dilutable self-microemulsifying delivery systems (SMEDS) formulated with lecithin (Le) and polyglycerol-10-caprylate (PG10C) at a ratio of 2/5. This surfactant blend was mixed with ethyl oleate (EOL) at a ratio of 60 surfactant/40 EOL to produce a D60 dilution line. This D60 SMEDS was diluted with 0.9% w/v NaCl solution to produce lecithin-linker µEs (LLMs). The properties of the resulting LLMs were predicted using the hydrophilic–lipophilic-difference (HLD) and net-average curvature (NAC) model, indicating that LLMs with aqueous content from 5% to 60% are bicontinuous, confirmed via viscosity and conductivity. The largest yeast activity and viability obtained with LLMs were achieved with 30% aqueous content, resulting from the balance between having enough water for the effective transport of metabolites, enough SMEDS to contribute nutrients and lipids, and a low enough water to limit the partition of PG10C that, when present in the aqueous phase, inhibited yeast activity. For SMEDS, its low water activity ensured that the yeast remained dormant, keeping them alive for at least 10 weeks. Full article

Microemulsions have been commonly used with various permeation enhancers to improve permeability through the skin. The purpose of this study was to compare the release and permeation ability of two commonly used permeation enhancers—diethylene glycol monoethyl ether (DGME) and oleyl alcohol—by the changes in oil composition, the addition of a gelling agent, and water content using ibuprofen as a model drug. Four microemulsions were formulated, selection was based on ternary phase diagrams, and physicochemical properties were evaluated. The release and permeation of the microemulsion formulations were performed in vitro by Franz cell studies on a regenerated cellulose membrane and a Strat-M^® membrane, respectively, and the amount of ibuprofen permeated and released was analyzed by high-performance liquid chromatography (HPLC). All four microemulsions were compatible with the skin pH, and the average pH ranged from 4.9 to 5.6. The average droplet size of the microemulsions ranged from 119.8 to 153.3 nm. Drug release was significantly the highest from the gel-based microemulsions (59% and 64%, p < 0.05). However, there was a fourfold difference in drug permeation from these gels—a significantly higher permeation from the microemulsion-gel containing oleic acid and oleyl alcohol compared to the DGME formulation. These results indicated that the microemulsion-gel with oleyl alcohol as the permeation enhancer could be a preferable formulation approach for the topical administration of ibuprofen. These results highlight the need for optimization of the microemulsion formulation to confirm the permeation-enhancing effects of chosen permeation enhancers despite being a well-known permeation enhancer. Full article

Patchouli oil (PO) is a natural substance famous for its immune-enhancing and anti-inflammatory effects. Atopic dermatitis (AD) is characterized by epidermal gene mutations, skin barrier dysfunction, and immune dysregulation, making patchouli volatile oil a potential candidate for AD treatment. Initially, PO was mixed with ethyl oleate (EO), castor oil ethoxylated ether-40 (EL-40), anhydrous ethanol, and water to form a patchouli oil microemulsion (PO-ME) system. The formulation ratios were optimized using the Box–Behnken design-effect surface method, and their products were characterized for type, particle size, polydispersity index (PDI), and appearance. Additionally, patchouli oil microemulsion gel (PO-MEG) was developed with a specified concentration of 1.5% carbomer-940 as the matrix, and its pH, stability, viscosity, and permeability were evaluated. We assessed the irritation tests of PO-MEG using a rat self-control model and the Cell Counting Kit-8 (CCK-8) assay. The results demonstrated that should be attributed to non-irritating. This study also assessed the efficacy of optimized PO-MEG on AD-like symptoms using a 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mouse model. Compared with the model group, the in vivo efficacy studies have shown the PO-MEG group significantly reduces dermatitis scores, mast cell counts, epidermal thickness, and levels of pro-inflammatory cytokines and immune factors in skin homogenates. This suggests that PO-MEG would become a safer topical formulation for treating atopic dermatitis. Full article

Background: Skin inflammation represents a hallmark of many skin conditions, from psoriasis to eczema. Here, we present a novel microemulsion formulation for delivering a low dose of potent immunosuppressant, tacrolimus, to the skin for local inflammation control. The efficacy of topically delivered tacrolimus in controlling skin inflammation can be enhanced by packaging it into microemulsions. Microemulsions are small-size, thermodynamically stable, and surfactant-rich emulsions that can enhance tissue penetration and local tissue retention of poorly soluble drugs, which can reduce dosing frequency and potentially improve patient compliance. Methods: We present a novel approach for microemulsion manufacturing that uses a combination of both low and high-energy methods. The microemulsion composition and manufacturing parameters were optimized by adopting Quality by Design methodologies. The FMECA (Failure, Mode, Effects, Criticality Analysis)-based risk assessment, D-optimal Design of Experiment (DoE), and statistical analysis of parameters impacting responses through the multiple linear regression (MLR) was implemented for identifying critical formulation and process parameters. Results: Through QbD strategy, a stable microemulsion with optimized drug loading that met all critical quality attributes (CQAs) was identified. The optimal microemulsion candidate was successfully scaled up three-fold with retained CQAs. The presented microemulsion showed a slow and extended drug release profile in vitro. Conclusions: Presented findings suggest that microemulsions are a promising novel approach for tacrolimus delivery to the skin. Further, we also demonstrated that a combination of low-energy emulsification and microfluidization processes can produce stable and robust microemulsions with small droplet size that can be implemented in drug delivery of poorly soluble anti-inflammatory drugs. To the best of our knowledge, this is the first report of QbD-driven optimization of microemulsion manufacturing by microfluidization. Full article

TiO₂ used for photocatalytic water purification is most active in the form of nanoparticles (NP), but their use is fraught with difficulties in separation from solution or/and a tendency to agglomerate. The novel materials designed in this work circumvent these problems by immobilizing TiO₂ NPs on the surface of exfoliated clay minerals. A series of TiO₂/clay mineral composites were obtained using five different clay components: the Na-, CTA-, or H-form of montmorillonite (Mt) and Na- or CTA-form of laponite (Lap). The TiO₂ component was prepared using the inverse microemulsion method. The composites were characterized with X-ray diffraction, scanning/transmission electron microscopy/energy dispersive X-ray spectroscopy, FTIR spectroscopy, thermal analysis, and N₂ adsorption–desorption isotherms. It was shown that upon composite synthesis, the Mt interlayer became filled by a mixture of CTA⁺ and hydronium ions, regardless of the nature of the parent clay, while the structure of Lap underwent partial destruction. The composites displayed high specific surface area and uniform mesoporosity determined by the size of the TiO₂ nanoparticles. The best textural parameters were shown by composites containing clay components whose structure was partially destroyed; for instance, Ti/CTA-Lap had a specific surface area of 420 m²g⁻¹ and a pore volume of 0.653 cm³g⁻¹. The materials were tested in the photodegradation of methyl orange and humic acid upon UV irradiation. The photocatalytic activity could be correlated with the development of textural properties. In both reactions, the performance of the most photoactive composites surpassed that of the reference commercial P25 titania. Full article

Rheumatoid arthritis, a chronic autoimmune disorder affecting millions worldwide each year, poses a significant threat due to its potential for progressive joint damage and debilitating pain if left untreated. Topical anti-inflammatory and analgesic treatments offer localized relief with reduced systemic side effects compared to conventional oral therapies, making them a promising option for managing rheumatoid arthritis. Therefore, the current study endeavored to formulate a microemulsion gel formulation loaded with diclofenac and curcumin for topical administration in the management of rheumatoid arthritis, utilizing Tea tree oil. The ratio of surfactant and cosurfactant was 4:1, assessed by pseudoternary phase diagram on the basis of the maximum emulsification region. The microemulsion underwent optimization using a Central Composite Rotatable Design (CCRD) with constraints of minimum particle size, polydispersity index, and maximum transmittance. The Curcufenac-T microemulsion had a particle size, polydispersity index (PDI), and transmittance of 151.82 ± 15.9 nm, 0.287 ± 0.021, and −5.78 ± 0.26 mV, respectively. DSC analyses confirmed the stability and compatibility of diclofenac and curcumin within the formulation. The microemulsion was changed into gel form by incorporating 1% carbopol-934. Skin permeation analysis revealed that the percentage of diclofenac permeated at 0.5 h from Curcufenac-T microemugel and the conventional gel was 12.1% and 3.9%, respectively, while at 12 h, the rates were 82.6% and 34.2%, respectively. In vitro permeability demonstrated significant potential for the effective delivery of diclofenac and curcumin to targeted sites, compared to conventional gel. Therefore, it was deduced that the Tea tree oil integrated diclofenac and curcumin microemulsion gel could enhance the effectiveness of diclofenac and serve as a promising vehicle for rheumatoid arthritis treatment. Full article

Skin pigmentation typically arises from the excessive secretion and accumulation of melanin, resulting in a darker complexion compared to normal skin. Currently, the local application of chemical drugs is a first-line strategy for pigmentation disorders, but the safety and efficacy of drugs still cannot meet clinical treatment needs. For long-term and safe medication, researchers have paid attention to natural products with higher biocompatibility. This article begins by examining the pathogenesis and treatment approaches of skin pigmentation diseases and summarizes the research progress and mechanism of natural products with lightening or whitening effects that are clinically common or experimentally proven. Moreover, we outline the novel formulations of natural products in treating pigmentation disorders, including liposomes, nanoparticles, microemulsions, microneedles, and tocosomes. Finally, the pharmacodynamic evaluation methods in the study of pigmentation disorder were first systematically analyzed. In brief, this review aims to collect natural products for skin pigmentation treatment and investigate their formulation design and efficacy evaluation to provide insights for the development of new products for this complex skin disease. Full article