Search Results (97)

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

Achieving precise control over anticancer drug release remains one of the key challenges in modern pharmaceutical development, as it directly determines therapeutic efficacy, systemic toxicity, and patient outcomes. This review critically evaluates recent advances in three major formulation strategies: polymeric solid dispersions, cyclodextrin-based inclusion complexes, and metal–organic frameworks (MOFs), with a particular focus on their capacity to tailor anticancer drug release. Over the past decade, polymeric solid dispersions and cyclodextrin-based carriers have played a central role in improving the dissolution and bioavailability of poorly water-soluble anticancer agents, while also enabling modified release profiles through rational formulation design. Increasing structural complexity, including ternary systems and supramolecular assemblies, reflects a shift toward more controllable delivery platforms. In recent years, MOFs have emerged as highly adaptable porous materials capable of supporting controlled and stimuli-responsive release. The integration of imaging agents, magnetic components, and photothermal functionalities has further enabled the design of multifunctional and theranostic platforms. Taken together, these technologies reflect a shift from conventional solubility enhancement toward structurally engineered systems designed to achieve predictable and controlled drug release. Continued advances in material design and formulation strategies are expected to further refine release kinetics and support the development of next-generation anticancer therapies aligned with the growing demand for precision medicine. 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

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

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 reports a self-assembled ternary delivery system composed of bovine serum albumin (BSA), Fe^(III), and 8-Shogaol (BSA-Fe^(III)-8S) to enhance the stability of this labile ginger-derived bioactive compound. Optimized nanoparticles prepared via one-pot coprecipitation exhibited a particle size of 115.14 nm, polydispersity index (PDI) of 0.084, zeta potential of +52.23 mV, encapsulation efficiency of 94.93%, and loading capacity of 23.73%. Spectroscopic analyses (FT-IR, UV–Vis, XPS) and fluorescence quenching confirmed the formation of a core–shell metal–phenolic network, where Fe^(III) coordinates with 8-Shogaol and BSA forms the outer protein shell. Compared to free 8-Shogaol, the BSA-Fe^(III)-8S MPN nanoparticles demonstrated significantly enhanced thermal, UV, and storage stability. During simulated gastrointestinal digestion, the nanoparticles retained 64.04% of 8-Shogaol, compared to only 51.38% for the free compound. Cytotoxicity assays on HEK293 cells confirmed the biocompatibility of the nanoparticles. This BSA-Fe^(III)-8S delivery system offers a promising strategy for protecting bioactive phenolic compounds, with potential applications in functional foods and nutraceutical formulations. Full article

Background: The oral delivery of biopharmaceuticals remains a major challenge for researchers and the pharmaceutical industry. Therefore, extensive research is ongoing to develop a viable delivery method, hence self-emulsifying drug delivery systems (SEDDSs) are being investigated because of their ability to protect the carried macromolecules in the gastrointestinal environment and facilitate absorption through the intestinal barrier. Objectives: To systematically investigate this promising method for the oral delivery of lysozyme (LYZ) and to model oral peptide/protein administration. Methods: LYZ/sodium dodecyl sulfate (SDS) hydrophobic ion pairs (HIPs) were prepared to enhance protein solubility and stability in SEDDSs. Different surfactants (Tween^® 20 and 80) and as co-surfactants (Span^® 20 and 80) were combined for the preparation of liquid SEDDSs according to a 2² full factorial design and samples of each combination were formulated based on a three-factor-constrained mixture design. The critical quality attributes (CQAs), droplet size, polydispersity index (PDI), and zeta potential were measured by dynamic light scattering (DLS). The process design space was determined by response surface methodology (RSM) and two-dimensional ternary contour plots. An in vitro release test was performed using the sample-and-separate approach. Results: Emulsions of SEDDSs with the optimal properties of droplet size < 200 nm, PDI < 0.4 and zeta potential < −10 mV were prepared. Consequently, a HIP load of 10 mg/g was achievable, exhibiting apparent first-order kinetics, with approximately 80% of the loaded LYZ released within 6 h. Conclusions: This study may contribute to better understanding of the effects and interactions of formulating materials for SEDDSs and their possible role in the oral delivery of biopharmaceuticals. Full article

Background/Objectives: Poor aqueous solubility of active pharmaceutical ingredients (APIs) remains a critical barrier to effective oral formulation. This study investigated the production of ketoprofen amorphous solid dispersions (ASDs) via hot melt extrusion (HME) using hydrophilic carriers and surfactants to enhance solubility and dissolution. Methods: ASDs were prepared by the fusion method employing mannitol or polyethylene glycol (PEG) 4000 hydrophilic carriers and further modified by addition of poloxamer 188 or poloxamer 407 as surfactants. Solubility was evaluated, and the best performing formulations were selected for HME to assess the effect of extrusion parameters (temperature, screw speed and re-extrusion) on API solubility and dissolution. Selected ASD extrudates were formulated into tablets and capsules and further tested. Results: Ternary ASDs exhibited higher solubility than their binary counterparts. The combinations of high-concentration hydrophilic carrier (mannitol or PEG 4000) and poloxamer 407 proved the most effective. The HME-produced ASDs showed superior solubility compared to the simple fusion method, with temperature being the most critical processing parameter, while screw speed and re-extrusion were carrier dependent, enhancing solubility for mannitol-based ASDs but not for PEG 4000; re-extrusion also led to mild color changes and technological issues preventing further processing. The selected ASD extrudates were successfully formulated into tablets and capsules with good physical characteristics and dissolution profiles. Conclusions: These findings demonstrate the need to further investigate the potential of re-extrusion strategies and surfactant-enhanced ASD systems for improving the oral delivery of poorly soluble drugs. Full article

Incorporating hydrophobic flavonoids such as naringenin into food systems is challenging due to their poor water solubility and instability. Effective delivery systems are essential to improve solubility, dispersibility, and controlled release during digestion. This study developed a food-grade encapsulation system using basil seed gum water-soluble extract (BSG-WSE) combined with proteins, sodium caseinate (NaCas) and whey protein isolate (WPI), via pH-driven and mild heat treatments in aqueous media, without the use of organic solvents, to ensure safety and sustainability. BSG-WSE and NaCas were tested at mass ratios of 1:1, 1:3, and 1:5 under pH conditions of 4, 5, and 7, followed by heat treatments at 60 °C or 80 °C for 30 min. The total biopolymer concentrations were 0.15%, 0.3%, and 0.45% (w/v). The most stable colloidal system was obtained at a 1:1 ratio, pH 4, and 60 °C, which was further evaluated for two additional flavonoids (rutin and quercetin) and with WPI as an alternative protein source. The highest loading capacity (11.18 ± 0.17%) and encapsulation efficiency (72.50 ± 0.85%) were achieved for naringenin under these conditions. Quercetin exhibited superior performance, with a loading capacity of 14.1 ± 3.12% and an encapsulation efficiency of 94.36 ± 5.81%, indicating a stronger affinity for the delivery system. WPI showed lower encapsulation efficiency than NaCas. Ternary systems (BSG-WSE, NaCas, and naringenin) formed under different pH and heat treatments displayed distinct morphologies and interactions. The pH 4 system demonstrated good dispersion and pH-responsive release of naringenin, highlighting its potential as a delivery vehicle for hydrophobic flavonoids. BSG-WSE significantly improved the stability of protein-based complexes formed via pH-driven assembly. Physicochemical characterization, rheological analysis, and release studies suggest that this system is particularly suitable for semi-solid food products such as yogurt or emulsions, supporting its application in functional food development. Full article

This study constructed ternary complexes of whey protein isolate (WPI), naringin (NAR), and sodium alginate (SA) and their stabilized emulsions, and characterized their physicochemical properties. The results confirmed interactions between NAR and SA with WPI, which induced quenching of WPI intrinsic fluorescence; formation of the ternary complexes could effectively inhibit WPI flocculation near its isoelectric point. Compared with the corresponding binary complexes, the WPI-NAR-SA ternary complexes developed more stable emulsions with smaller droplet sizes and higher absolute ζ-potential values, exhibiting superior storage stability that increased with SA concentration. After storage at 4 °C for 20 days, the emulsion system exhibited a peroxide value remaining below 4.7 μg/mL; after 9 days of UV irradiation, lutein retention reached 82.49%. Both protective effects increased with rising SA concentration. This study provides a strategy for the development of a novel functional emulsion delivery system. Full article

The present study investigates the magnetohydrodynamic (MHD) flow characteristics of a blood-based ternary nanofluid (Au/Cu/Al₂O₃-blood) in stenosed arteries, with a focus on symmetry-inspired modeling rooted in the axial symmetry of arterial geometry and the symmetric distribution of external physical fields (magnetic field, thermal radiation). The findings offer significant insights into the realm of hyperthermia therapy and targeted drug delivery within the domain of biomedical engineering. A mathematical model is established under a cylindrical coordinate system (consistent with arterial axial symmetry), integrating key physical effects (thermal radiation, chemical reactions, viscous dissipation, body acceleration) and fractional-order dynamics via Caputo derivatives—while ensuring the symmetry of governing equations in time and space. The numerical solutions for velocity and temperature profiles are obtained using the Laplace transform and Concentrated Matrix-Exponential (CME) method, a technique that preserves symmetric properties during the solution process. The results of the study indicate the following: The Hartmann number, which is increased, has been shown to reduce axial velocity due to the Lorentz force, thereby maintaining radial symmetry. Furthermore, thermal radiation has been demonstrated to raise fluid temperature, a critical factor in heat-based therapies, with the temperature field evolving symmetrically. In addition, it has been observed that ternary nanoparticles outperform single and binary systems in heat and mass transfer via symmetric dispersion. This work contributes to the existing body of knowledge by integrating symmetry principles into the study of fractional dynamics, electromagnetic fields, and body acceleration modeling. It establishes a comprehensive biomedical flow framework. It is imperative that future research explore pulsatile flow under symmetric boundaries and validate the model through experimental means. 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

Endometriosis is a common gynecological condition that affects fertility in many women of reproductive age worldwide. This multifaceted disease exhibits a pathogenesis characterized by hormonal and immune system dysregulations, alongside increased angiogenic activity within the peritoneum. The aberrant proliferation of endometrial tissue outside the uterus is associated with vascularization in ectopic endometriotic lesions. Consequently, RNA interference (RNAi)-based angiogenic therapies targeting the VEGFA gene present a promising strategy for the treatment of endometriosis. To ensure the efficacy of RNAi-based therapy, it is critical to develop carriers capable of precisely delivering small interfering RNA (siRNA) to target cells. Additionally, the instability of polyplexes in vivo must be regarded as a pivotal aspect influencing the success of non-viral delivery. In this study, we introduce ternary polyplexes comprising siRNA and a carrier derived from an arginine–histidine-rich peptide, which is further coated with a glutamate–histidine-rich polymer modified using an SDF-1 chemokine-derived ligand for targeting CXCR4-expressing cells. The physicochemical characteristics of the siRNA-polyplexes, along with cellular toxicity and GFP gene silencing efficacy, were assessed in vitro. The anti-angiogenic potential of anti-VEGFA siRNA-polyplexes was evaluated by measuring the size of endometrial lesions, conducting immunohistochemical staining, and analyzing VEGFA gene expression. For in vivo experiment, a rat model of endometriosis induced by subcutaneous auto-transplantation of uterine tissue was utilized. A significant reduction in the growth of endometriotic implants and silencing of VEGFA gene expression was observed when compared to the saline-treated control group. The results of this study strongly suggest that the developed ternary polyplexes have significant potential as an efficient tool for the development of anti-angiogenic RNAi-based therapies for endometriosis. 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