Search Results (164)

Background/Objectives: The fruit of Medinilla speciosa Blume fruit contains flavonoids with potent activity against Cutibacterium acnes, but their clinical application is hindered by poor bioavailability. This study aimed to develop, characterize, and evaluate a phytosome-based vesicular system to enhance the in vivo antibacterial efficacy of the fruit’s ethyl acetate fraction (EAFMS). Methods: Phytosomes were synthesized via antisolvent precipitation using a 1:3 EAFMS-to-phospholipid ratio. Formulations were characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), and in vitro release. Antibacterial efficacy was assessed in C. acnes-induced Wistar rats over three days. Results: EAFMS showed superior antibacterial activity with a 93.5% relative potency compared to tetracycline. The optimized phytosomes exhibited favorable physicochemical properties: particle size of phytosome 244.60 ± 0.85 nm, PDI of phytosome 0.396 ± 0.08, zeta potensial of phytosome −56.70 ± 2.08 mV, and EE of phytosome 89.46 ± 0.45%. The formulation achieved a 76.504% cumulative release at 8 h. In vivo trials demonstrated that the phytosome cream significantly reduced bacterial colony counts and diminished inflammatory cell infiltration compared to the cream base. Conclusions: The phytosome system effectively improves the stability and delivery of M. speciosa flavonoids, significantly enhancing their antibacterial and anti-inflammatory performance against acne. Full article

Oxyresveratrol (Oxy) exhibits a diverse range of biological activities. However, its practical application is constrained by low aqueous solubility and chemical instability. In this work, Oxy-loaded zein (Z) nanoparticles (NPs) stabilized by a sodium alginate (Alg) coating (Oxy-Z/Alg NPs) were fabricated using an antisolvent precipitation method. The absence of crystalline peaks in X-ray diffraction analysis suggested that Oxy was dispersed as an amorphous phase in NPs, while the Fourier transform infrared spectra identified strong interfacial associations between the components. The stabilization of the NPs is attributed to the site-specific binding of Oxy with Z’s SER-162 and GLN-174 residues. Molecular docking, molecular dynamics simulations, and differential scanning calorimetry profiles evidenced the formation of intermolecular hydrogen bonds. Dynamic light scattering analysis showed that the nanocomplexes had a nano-scale dimension (243 ± 6 nm) and a zeta potential of −36 mV. SEM micrographs revealed that the NPs possessed a spherical morphology. The NPs exhibited colloidal stability against prolonged heating (80 °C for 75 min), ionic strengths (up to 100 mM NaCl), and pH range (2.0–10.0). Encapsulation within the Alg coating enhanced Oxy’s antioxidant capacity over its unprotected form by shielding its core bioactivity from degradation. The Oxy-Z/Alg nano-system shows significant promise for the encapsulation of Oxy, providing a practical basis for its integration into nutraceuticals and functional food fields. Full article

The development of new pharmaceutical forms with high solubility and enhanced bioavailability currently represents a significant challenge in the pharmaceutical industry. Currently, methods are still being explored to improve the oral bioavailability of Rivaroxaban, estimated to be 60%, due to its low solubility. To address these challenges, this study uses the antisolvent precipitation method to obtain three nanosuspensions of rivaroxaban (RIV), using Poloxamer 188 (P188) and hydroxypropyl methylcellulose (HPMC) by varying their concentrations (1:1:1, 1:1:2, and 1:2:1 molar ratios). The RIV nanosuspensions were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The antisolvent precipitation method led to the successful formulation of the three RIV nanosuspensions. Afterward, the formulated tablets containing dry RIV nanosuspensions were pharmaceutically characterized. RIV-P188-HPMC (1:1:1) and RIV-P188-HPMC (1:2:1) dry nanosuspensions demonstrated a uniform flow, and they were subsequently analyzed to establish the in vitro dissolution profile. The nanosuspension formulation with a higher content of P188 showed superior performance. Overall‚ the results of this study show that the antisolvent precipitation method in the presence of different amounts of HPMC and P188 is very efficient in increasing the dissolution rate of rivaroxaban to achieve its better efficiency. Full article

Background: Non-small cell lung cancer (NSCLC), a malignant tumor with high global incidence and mortality rates, urgently requires more effective targeted drug delivery systems for its treatment. As an EGFR tyrosine kinase inhibitor, gefitinib has its clinical efficacy limited by poor solubility and low bioavailability. This study aimed to develop a gefitinib–salicylic acid salt (Gef-Sa) and its nano-formulation (Gef-Sa-NPs) via a combined strategy of crystal engineering and nanotechnology to improve its pharmaceutical properties. Methods: Gef-Sa was prepared using a suspension method, and its salt formation and thermal stability were predicted by the ΔpKa rule and confirmed by various solid-state characterization techniques, including single crystal/powder X-ray diffraction, thermal analysis, and infrared spectroscopy. Gef-Sa-NPs were prepared via an ultrasound-assisted anti-solvent precipitation method. Their performance was evaluated through in vitro dissolution tests, pharmacokinetic studies, and in vitro antitumor experiments. Results: Gef-Sa-NPs with a particle size of 31 nm (PDI = 0.15) were successfully prepared. In vitro dissolution tests demonstrated that the nano-formulation exhibited a significantly higher dissolution rate in pH 1.2, pH 4.5, pH 6.8 and pure water when compared with the raw drug (p < 0.01). Pharmacokinetic studies revealed that Gef-Sa and Gef-Sa-NPs increased the oral bioavailability in rats to 1.5-fold and 1.9-fold that of the raw drug, respectively. In vitro antitumor experiments confirmed that the Gef-Sa-NPs increased the inhibition rate against A549 cells compared with the Gef. Conclusions: This study innovatively combines salt formation and nanonization technologies to systematically address the key issue of the poor solubility of Gef. The resulting nano-formulation demonstrates excellent dissolution characteristics, pharmacokinetic behavior, and antitumor efficacy. This strategy not only provides a novel drug delivery system with translational potential for NSCLC treatment but also offers a paradigm for the formulation design of poorly soluble drugs. Subsequent research will focus on scaling up production and evaluating pre-clinical safety. Full article

In this study, we investigated how the formation and properties of Pickering emulsions (PEs) stabilized by zein/tannic acid particles (ZTAPs) are impacted by the method used to generate the particles, before or during emulsification. ZTAPs were obtained through two antisolvent precipitation methods (sequential and co-precipitation) across zein/tannic acid molar ratio (R) range of 1/0 to 1/30. Emulsions were prepared using four methods, either with pre-formed ZTAPs or by mixing zein and tannic acid immediately before or during emulsification. The results indicated that pre-forming the particles prior to emulsification is crucial for controlling droplet size and homogeneity, while the quantity of tannic acid plays a supporting role. Tannic acid is not only critical for emulsion stabilization but also imparts its antioxidant activity to the emulsions. This activity is also controlled by the molar ratio R of the particles and the preparation protocol. ZTAPs are promising plant-based stabilizers for emulsions in the food and pharmaceutical industries. These findings provide a better understanding of the importance of their method of production in controlling the characteristics (droplet size, stability, and antioxidant properties) of the emulsions they stabilize. Full article

Background/Objectives: This study addresses the need for scalable and predictive strategies linking mixing conditions to nanocarrier properties by developing and analyzing a coaxial jet antisolvent process for the continuous production of pharmaceutical nanocarriers. Methods: A single experimental platform was used to generate both curcumin-based nanoparticles and nanoliposomes, enabling direct comparison of how mixing regime and formulation variables influence product characteristics. Results: Fluid-dynamic behavior was first characterized using tracer and micromixing experiments, revealing a strong dependence of mixing time on flow conditions, with characteristic mixing times decreasing from >1000 ms under laminar conditions to approximately 10–30 ms in turbulent regimes. Nanoparticles and liposomes obtained under optimized conditions exhibited mean sizes in the range of 120–250 nm, with polydispersity indices typically below 0.2 under optimized turbulent conditions. To rationalize these observations, a computational framework was implemented, combining Reynolds-averaged computational fluid dynamics with a population balance formulation solved by the method of moments. The model provided spatially resolved insight into solvent exchange, supersaturation development, and nucleation–growth dynamics, showing good agreement with experimental trends and capturing the effect of mixing conditions on particle size across different regimes. Conclusions: Although simplified, the modeling approach establishes the basis for future extensions toward full population-balance distribution simulations capable of predicting complete particle size distributions, highlighting the ability of the coaxial jet mixer to control supersaturation and particle formation through tunable hydrodynamic conditions. This capability makes the system particularly attractive compared to conventional batch or less controllable mixing technologies, enabling a more rational and scalable design of pharmaceutical nanocarriers, with good encapsulation performance as discussed in the main text. Full article

Naringenin (NRG), a poorly water-soluble flavonoid with anticancer potential, suffers from limited bioavailability due to low aqueous solubility and poor membrane permeation. In this study, NRG nanocrystals (NRG-NCs) were developed using an optimized antisolvent precipitation–probe sonication method and incorporated into a 20% (w/w) Pluronic^® F127 hydrogel for enhanced delivery. The optimized NRG-NCs exhibited a mean particle size of ~195 ± 5 nm, polydispersity index of ~0.20 ± 0.02, and zeta potential of −24 ± 3 mV. Percentage yield and drug loading capacity were 88.6 ± 2.3% and 78.4 ± 1.8%, respectively. Nanocrystal formation resulted in ~9-fold enhancement in saturation solubility compared to raw NRG. The NRG-NCs gel demonstrated rapid dissolution (~90% release within 120 min) and ~2.5-fold higher ex vivo permeation across the Strat-M^® membrane relative to pure NRG. The hydrogel exhibited suitable physicochemical properties (viscosity ~12,850 cP; pH 6.2 ± 0.1; spreadability 5.8 ± 0.3 cm) and maintained >92% drug content after 30 days of refrigerated storage. Mechanistic studies revealed dose-dependent cytotoxicity, characterized by increased intracellular ROS, mitochondrial membrane depolarization, and elevated caspase-3 activity, confirming ROS-mediated apoptosis. In conclusion, the nanocrystal–hydrogel platform significantly enhances the solubility, permeation, and pro-apoptotic efficacy of NRG, demonstrating its potential for skin cancer treatment. Full article

Polyphenols are structurally diverse plant secondary metabolites with broad biological activities and growing applications across the food, health, and materials sectors. Conventional extraction based on organic solvents (e.g., methanol, ethanol) is often energy-intensive, inefficient, and environmentally burdensome. Ionic liquids (ILs) and deep eutectic solvents (DESs) have therefore emerged as greener alternatives for polyphenol extraction. This review evaluates recent advances in solvent design, extraction performance, and process sustainability. Imidazolium-based ILs frequently achieve high yields and selectivity, particularly when coupled with ultrasound or microwave-assisted extraction, but high cost, synthetic complexity, viscosity-related constraints, and potential toxicity hinder scaleup. By contrast, DESs—especially those derived from choline chloride or lactic acid—are easier to prepare, less costly, and more compatible with industrial implementation, with efficiency enhanced by tailoring hydrogen bond networks, water content, and process intensification. Critical downstream challenges persist for both solvent classes, notably in extract purification and solvent recovery due to low volatility; approaches such as resin adsorption, antisolvent precipitation, and direct formulation have been explored. Overall, ILs and DESs represent compelling alternatives to conventional solvents, and future progress will depend on integrated extraction–recovery strategies, systematic solvent selection, and validation under scalable, sustainable processing conditions. Full article

This study aimed to slow down starch digestion by encapsulating the starch granule within a firm zein shell via solvent-exchange-induced zein deposition. The zein shell adhered tightly to the granule surface and the shell thickness increased with increasing zein concentration. The average shell thickness of microparticles produced with zein (1%, 2%, and 3% w/v) was 0.54 μm, 0.97 μm, and 1.63 μm, respectively. Thicker zein shells acted as a mechanical barrier limiting heat transfer and water penetration, thus significantly affecting the starch digestibility. The in vitro simulated digestion experiment indicated that CS-3% zein microparticles exhibited an approximately 19-fold higher resistant starch (RS) content compared with native corn starch. These findings demonstrated the potential of the zein acting as a shell material in developing delivery system for controlled starch digestion. Additionally, this study validated antisolvent precipitation as an effective method to construct hydrophilic core/hydrophobic shell delivery systems to encapsulate unstable and hygroscopic compounds. Full article

Lignin, the second-most-abundant polymer on Earth, has attracted attention for its value-added applications. Colloidal lignin particles can overcome handling and compatibility issues, offer antioxidant, antimicrobial, and UV-protective properties, and serve as Pickering stabilizers. Plant extracts rich in bioactive compounds, such as polyphenols and flavonoids (e.g., quercetin), can further enhance lignin-based formulations. In this context, colloidal lignin–quercetin particles (CLQPs) were produced for the first time via antisolvent precipitation and used as Pickering emulsion stabilizers. CLQP dispersions (30 g/L) were prepared by solubilizing lignin and quercetin in 80% (v/v) aqueous acetone solution, followed by precipitation with a pH 8 buffer. A quercetin content of 50% (w/w) (CLQP-50) resulted in predominantly round-shaped lignin–quercetin particles (<1 µm) with a small fraction of quercetin crystals. Both structures contributed to emulsion stabilization, as evidenced by confocal microscopy, a three-phase contact angle of 91.6 ± 0.1°, and a zeta potential of −52.8 ± 2.7 mV. CLQP-50 successfully stabilized Pickering emulsions at a 60/40 oil/water ratio, showing high physical stability (stability index 0.01) and shear-thinning behavior with gel-like consistency. These findings demonstrate the pioneering development of lignin–quercetin hybrid colloidal particles as sustainable and functional Pickering stabilizers, opening new opportunities for advanced cosmetic and pharmaceutical formulations. Full article

This study developed a transdermal drug delivery system for Rheumatoid Arthritis (RA) using a dual-network hydrogel microneedle patch loaded with methotrexate nanocrystals (DHMN@MTX-NCs), and explored its synergistic therapy with Adalimumab (ADA) for a painless, long-acting, and targeted RA treatment. This study synthesized Methacrylated Hyaluronic Acid and Methacrylated Gelatin. MTX-NCs were prepared by solvent-antisolvent precipitation and incorporated into a dual-network hydrogel microneedle patch via centrifugal molding. Evaluations included pharmaceutical properties, mechanical strength, drug release, in vitro anti-inflammatory effects on RAW 264.7 cells, and therapeutic efficacy in a rat RA model. The experimental results show that the prepared MTX-NCs present a spherical shape, an average size of 325.72 nm, a PDI of 0.154, and a drug-loading capacity of 61.3%. The microneedle patch exhibited high puncture efficiency and suitable swelling. In vitro, DHMN@MTX-NCs combined with ADA most strongly inhibited macrophage migration, upregulated IL-10, and downregulated TNF-α, IL-1β, NO, iNOS, and COX-2. In vivo, both monotherapy and combination therapy reduced joint swelling, bone erosion, and histopathological damage. Ultimately, the study demonstrated the synergistic anti-inflammatory efficacy of DHMN@MTX-NCs combined with ADA, providing a novel, non-invasive, and targeted therapeutic strategy for RA. Full article

Background/Objectives: MHY498, a tyrosinase inhibitor, exhibits poor water solubility, which limits its topical delivery. Despite the importance of solubility data in rational formulation design, comprehensive information on its solubility behavior in various solvents and across a range of temperatures remains limited. Thus, this study aimed to systematically evaluate the solubility characteristics of MHY498 and to develop a nanosuspension formulation using an antisolvent precipitation approach to facilitate the development of an optimized topical formulation. Methods: In this study, we measured the solubility of MHY498 in various monosolvents and diethylene glycol monoethyl ether (DEGME) + water solvent mixtures at 293.15–313.15 K using a solid–liquid equilibrium technique. Based on these solubility data, MHY498 nanosuspensions were prepared via antisolvent precipitation guided by a Box–Behnken design matrix. In vitro skin permeability was also assessed using a Franz diffusion cell system to assess the topical delivery potential of the MHY498 nanosuspensions. Results: Among the investigated monosolvents, MHY498 exhibited the highest solubility in dimethylformamide, dimethylacetamide, DEGME, while the lowest solubility was observed in water. The solubility increased with temperature and DEGME content in solvent mixtures, and the experimental data were well described by thermodynamic and semi-empirical models, indicating an endothermic and spontaneous dissolution process. Solvent–solute interaction analysis revealed that hydrogen-bonding and nonspecific polarity interactions played key roles in enhancing MHY498 solubility. All nanosuspensions prepared within the design space exhibited particle sizes below 150 nm, and the optimized formulation achieved an average particle size of 28.1 nm. The optimized nanosuspension demonstrated a 3.3-fold increase in the cumulative permeated amounts compared with the conventional microsuspension. Conclusions: These findings demonstrate that a rational solvent selection strategy based on thermodynamic solubility analysis and antisolvent precipitation enables effective nanosuspension formulation of MHY498. The DEGME–water system was identified as a formulation-relevant solvent environment that supports both adequate drug solubilization and reproducible formation of nanosized particles. The resulting nanosuspension exhibited favorable particle size characteristics and enhanced formulation feasibility for topical applications. Therefore, it was shown that the developed nanosuspension system, established through a solubility-driven systematic approach, represents a promising strategy for improving topical delivery of MHY498. Full article

As a natural flavonoid compound, quercetin possesses excellent antioxidant, anti-inflammatory and anti-atherosclerotic activities. However, the poor water solubility and sensitivity to the environment severely limit the application of quercetin. Initially, quercetin-loaded zein/carboxymethyl chitosan nanoparticles (ZCQ NPs) were prepared using an anti-solvent precipitation method. The fabricated ZCQ NPs exhibited a small particle size and polydispersity index (PDI). The ZCQ NPs had a negative zeta potential with an absolute value of 41.50 ± 1.76 mV. ZCQ NPs could remain highly stable against light, heat and ion strength. In addition, ZCQ NPs maintained good monodispersity and displayed minimal changes in particle size under long-term storage conditions. Additionally, a superior antioxidant capacity of ZCQ NPs was also observed in the free radical and reactive oxygen species (ROS) scavenging study compared to that of free quercetin. All these results of this study suggest that ZCQ NPs could serve as an effective drug delivery system for encapsulating and delivering quercetin. Full article

Background/Objectives: A carrier-free self-assembled nanomedicine delivery system refers to a high drug-loading nanomedicine delivery system prepared by one or more active drug ingredients through supramolecular self-assembly, which has the advantages of high drug-loading and a simple preparation process, enabling multidrug synergistic therapy. 10-hydroxycamptothecin (HCPT) have active antitumor effects. Pentacyclic triterpenes are natural active components with a wide range of pharmacological activities. This study aimed to investigate the impact of structural types on the self-assembly of pentacyclic triterpenes and HCPT. Methods: Molecular docking studies were performed. Self-assembled nanoparticles were designed by co-assembling ursolic acid (UA), asiatic acid (AA), oleanic acid (OA), and betulinic acid (BA) with HCPT via anti-solvent precipitation combined with ultrasonication, followed by characterization. Cytotoxicity assays using the CCK-8 method revealed that the prepared self-assembled nanoparticles exhibited concentration-dependent inhibitory effects against A375, AGS, HCT-116, and HepG2 tumor cells. Confocal laser scanning microscopy (CLSM) indicated that UA/HCPT nanoparticles (UA/HCPT-NPs) were more efficiently internalized and accumulated in cells compared with the UA + HCPT physical mixture. Results: Both in vitro and in vivo results demonstrated that the self-assembled nanoparticles significantly enhanced antitumor efficacy while exerting minimal toxicity on major organs within the tested dose range. Conclusions: In summary, these findings highlight that pentacyclic triterpenoids components possess significant self-assembly potential, and that dual-drug co-delivery via self-assembled nanoparticles represents as a promising strategy for cancer therapy. Full article

Non-thermal plasma (NTP) is a fast, reagent-free technology for dye removal, yet its performance is highly dependent on the operating conditions and on plasma–catalyst interactions. In this work, a coaxial falling-film dielectric barrier discharge (DBD) reactor was optimized for the degradation and decolorization of organic dyes, with ceria (CeO₂) employed as a catalyst. For the first time, CeO₂ prepared via a supercritical antisolvent (SAS) micronization route was tested in plasma-assisted dye decolorization and directly compared with its non-micronized counterpart. Optimization of plasma parameters revealed that oxygen feeding, an input voltage of 12 kV, a gas flow of 0.2 NL·min⁻¹, and an initial dye concentration of 20 mg·L⁻¹ resulted in the fastest decolorization kinetics. While the anionic dye Acid Yellow 36 exhibited electrostatic repulsion and negligible plasma–ceria synergy, the cationic dyes Crystal Violet and Methylene Blue showed strong adsorption on the negatively charged CeO₂ surface and pronounced plasma–catalyst synergy, with SAS-derived CeO₂ consistently outperforming the non-micronized powder. The SAS catalyst, characterized by a narrow particle size distribution (DLS) and spherical morphology (SEM), ensured improved dispersion and interaction with plasma-generated species, leading to significantly shorter decolorization radiation times compared to the literature benchmarks. Importantly, this enhancement translated into higher energy efficiency, with complete dye removal achieved at a lower specific energy input than both plasma-only operation and non-micronized CeO₂. Scavenger tests confirmed •OH radicals as the dominant oxidants, while O₃, O₂•⁻, and e⁻_a played secondary roles. Tests on binary dye mixtures (CV + MB) revealed synergistic decolorization under plasma-only conditions, and the CeO₂-SAS catalyst maintained high overall efficiency despite competitive adsorption effects. These findings demonstrate that SAS micronization of CeO₂ is an effective material-engineering strategy to unlock plasma–catalyst synergy and achieve rapid, energy-efficient dye abatement for practical wastewater treatment. Full article