Search Results (1,293)

Hypericum perforatum L. (H.P.), a plant renowned for its wound-healing properties, was investigated for antioxidant/antimicrobial efficacy, toxicological safety, and in vivo wound-healing effects in this research to develop and characterize novel nanoemulsion hydrogel (NG) formulations. NG were prepared via emulsion diffusion–solvent evaporation and polymer hydration using Cremophor RH40 and Ultrez 21/30. A D-optimal design optimized oil/surfactant ratios, considering particle size, PDI, and drug loading. Antioxidant activity was tested via DPPH, ABTS⁺, and FRAP. Toxicological assessment followed HET-CAM (ICH-endorsed) and ICCVAM guidelines. The optimized NG-2 (NE-HPM-10 + U30 0.5%) demonstrated stable and pseudoplastic flow, with a particle size of 174.8 nm, PDI of 0.274, zeta potential of −23.3 mV, and 99.83% drug loading. Release followed the Korsmeyer–Peppas model. H.P. macerates/NEs showed potent antioxidant activity (DPPH IC₅₀: 28.4 µg/mL; FRAP: 1.8 mmol, Fe²⁺/g: 0.3703 ± 0.041 mM TE/g). Antimicrobial effects against methicillin-resistant S. aureus (MIC: 12.5 µg/mL) and E. coli (MIC: 25 µg/mL) were significant. Stability studies showed no degradation. HET-CAM tests confirmed biocompatibility. Histopathology revealed accelerated re-epithelialization/collagen synthesis, with upregulated TGF-β1. The NG-2 formulation demonstrated robust antioxidant, antimicrobial, and wound-healing efficacy. Enhanced antibacterial activity and biocompatibility highlight its therapeutic potential. Clinical/pathological evaluations validated tissue regeneration without adverse effects, positioning H.P.-based nanoemulsions as promising for advanced wound care. Full article

The aim of this study was to investigate the effect of Ostwald ripening inhibitors on D-limonene (D-LMN) nanoemulsions and to elucidate their impact on oral cancer cells. Various inhibitors, including olive oil, soybean oil, and perilla oil, were incorporated into D-LMN nanoemulsions at different ratios (25:75–75:25, D-LMN to inhibitor). The resulting nanoemulsions were evaluated for droplet size, size distribution, zeta potential, stability, droplet morphology, cytotoxicity, antimetastatic and anti-invasive activities, apoptosis induction, and cell cycle arrest. Results showed that the 75:25 D-LMN to inhibitor ratio produced the smallest droplet size and exhibited great stability, particularly with perilla oil. Notably, D-LMN nanoemulsions displayed strong anti-oral cancer effects by reducing cell viability, metastasis, and invasion. Apoptosis was induced, as evidenced by nuclear fragmentation, Annexin V binding, and altered expression of BAX, BCL-XL, Cytochrome c, and Caspase-9. Additionally, the nanoemulsions caused cell cycle arrest via downregulation of Cyclin D1, CDK2, CDK4, and CDK6. These findings highlight the potential of D-LMN nanoemulsions as a promising alternative therapeutic strategy for oral cancer treatment. Full article

A uniformly dispersed carbon nanotubes (CNTs)/polyvinyl alcohol (PVA) nano-colloidal emulsion was synthesized by leveraging colloidal stability and interfacial chemical interactions. This study systematically investigated the influence of the CNTs/PVA nano-colloidal emulsion on the mechanical properties, drying shrinkage, capillary water absorption, and microstructure of cement-based materials, while elucidating the underlying reinforcement mechanisms. The experimental results demonstrated that different CNTs/PVA ratios enhanced the concrete properties: For instance, 0.3% CNTs and 1.0% PVA improved the 28-day compressive and flexural strengths by 15% and 10%, respectively, while 0.5% CNTs and 1.0% PVA reduced the drying shrinkage by 76%, 34%, 22%, and 21% at 7, 28, 180, and 360 days. Additionally, the 0.5% CNTs/1.0% PVA mixture achieved a 25.7% lower absorption rate (25.25 vs. 34.00 g·m⁻², *p* < 0.001) than plain concrete. A microstructural analysis revealed that the CNTs/PVA composite formed an interpenetrating network within the cement matrix, which correlated with the observed mechanical improvements and shrinkage reduction. These findings indicate that even minimal additions of CNTs/PVA could effectively enhance the tensile and flexural capacity of concrete while mitigating its susceptibility to drying shrinkage. Full article

Mammary gland tumors in dogs are very common in clinical practice. Betulinic acid is currently a compound considered to have anticancer properties in human mammary tumors via nanoemulsions. In this study, betulinic acid nanoemulsions with a particle size of less than 300 nm were prepared. Biopsies were obtained from five female dogs with mammary tumors for histopathological analysis, confirming that two were tubular mammary carcinomas (MMTs, malignant) and three were complex mammary adenomas (BMTs, benign). The five female dogs were administered with a daily oral dose of nanoemulsion containing 5 mg/kg of betulinic acid for 30 days. Tumor size was measured every 7 days, and the response to treatment was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors) standards. In one of the females with MMTs treated with the nanoemulsion, the tumor size was reduced by approximately 38%, while in the BMT female dogs, the nanoemulsion reduced the tumor size by 25.3%. It was concluded that oral administration of betulinic acid nanoemulsions reduced the size of canine mammary tumors. Experimental studies are still needed to further evaluate this preparation. Full article

Background/Objectives: The main biologically active molecules of Cannabis sativa L. are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Both exert anticonvulsant effects when evaluated as single drugs, but their possible interaction as components of C. sativa extracts has been scarcely studied. For this reason, we evaluated CBD and THC, combined or not, in two seizure models in mice, using an improved vehicle formula. Methods: Firstly, acute seizures were induced by intraperitoneal (i.p.) pentylenetetrazole (PTZ, 80 mg/kg), and mice received CBD or THC at 1, 3, 6, and 10 mg/kg, or a CBD/THC 1:1 combination at 1.5, 3, and 6 mg/kg, per os (p.o.), one hour before PTZ administration. Secondly, mice received p.o. CBD (10 mg/kg), CBD/THC (1.5, 3, and 6 mg/kg), valproic acid (50 mg/kg), or vehicle (nanoemulsions without CBD or THC), one hour before PTZ (30 mg/kg, i.p.) every other day for 21 days. Behavioral, biochemical, and immunohistochemical analyses were performed to assess the response to PTZ, oxidative stress, and astroglial activation. Results: In the acute model, CBD and THC at 3–10 mg/kg, and their combinations, significantly increased latency to generalized seizures and death, and improved survival rates. In the chronic model, similarly to valproic acid, CBD 10 mg/kg and CBD/THC at 1.5 and 3 mg/kg delayed kindling acquisition, while CBD/THC 6 mg/kg had no effect. CBD and CBD/THC treatments reduced oxidative and nitrosative stress and attenuated astrogliosis, as indicated by decreased glial fibrillary acidic protein and GABA transporter 1 expression and increased inwardly rectifying potassium channel 4.1 expression in hippocampal regions. However, no cannabinoid treatment prevented the impairment in novel object recognition and Y maze tests. Conclusions: These findings support the potential role of cannabinoids in counteracting seizures, possibly by reducing oxidative stress and astrogliosis. The study also highlights the importance of nanoemulsions as a delivery vehicle to enhance cannabinoid effectiveness while considering the risks associated with direct cannabinoid receptor activation. Full article

Background/Objectives: Continuous manufacturing is gaining importance in the nanopharmaceutical field, offering improved process efficiency and product consistency. To fully leverage its potential, the integration of Process Analytical Technology (PAT) tools is essential for real-time quality control and robust process monitoring. Among the critical quality attributes (CQAs) of nanosystems, particle size plays a key role in ensuring product consistency and performance. However, real-time size monitoring remains challenging due to complex process dynamics and nanosystem heterogeneity. Methods: This study evaluates the applicability of conventional Dynamic Light Scattering (DLS) and spatially resolved DLS (SR-DLS) using the NanoFlowSizer (NFS) as PAT tools in a temperature-regulated top-down nano-production line. Various lipid-based nanosystems, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsions (NEs), were investigated. To ensure reliable implementation, key factors such as sample dilution, viscosity, focus position, measurement angle and temperature effects were systematically assessed for offline and at-line DLS using the Litesizer 500, as well as for offline, inline, and online SR-DLS using the NFS. Results: Offline screening confirmed that selecting the appropriate dilution medium and rate ensures measurement reliability. At-line methods provided an efficient alternative by enabling rapid final product control with minimal manual intervention. Inline and online monitoring further enhanced process efficiency by enabling real-time tracking of size, reducing waste, and allowing immediate process adjustments. Conclusions: This study demonstrates that integrating offline, at-line, in-line, and online DLS techniques allows for comprehensive product monitoring throughout the entire production line. This approach ensures a streamlined process, enables real-time adjustments, and facilitates reliable quality control after production and during storage. Full article

Periodontitis is a prevalent oral condition worldwide. Azithromycin, a conventional lipophilic drug for periodontal treatment, often causes systemic side effects when administered orally. To address this, azithromycin-loaded nano-emulgels were developed using olive oil as a carrier within a xanthan gum aqueous gel phase. This oil-in-aqueous gel emulsion was actuated into a foam for localized drug delivery in gingival and periodontal disease. The solubility of azithromycin in various vehicles was tested, with olive oil showing the best solubility (0.347 mg/mL). Thermodynamic stability testing identified viable nano-formulations, with encapsulation efficiencies ranging from 98 to 100%. These formulations exhibited rapid drug release within 2–8 h. Muco-adhesion studies and ex vivo permeability tests on porcine buccal mucosa highlighted the beneficial properties of xanthan gum for local drug retention within the oral cavity. Antimicrobial efficiency was assessed using minimum inhibitory concentrations against various oral pathogens, where the formulation with equal surfactant and co-surfactant ratios showed the most potent antibacterial activity, ranging from 0.390 to 1.56 µg/mL. This was supported by the shear-thinning, muco-adhesive, and drug-retentive properties of the xanthan gel base. The study also examined the influence of the oil phase with xanthan gum gel on foam texture, rheology, and stability, demonstrating a promising prototype for periodontitis treatment. Full article

The tumor microenvironment (TME) has a major role in malignancy and its complex nature can mediate tumor survival, metastasis, immune evasion, and drug resistance. Thus, reprogramming or regulating the immunosuppressive TME has a significant contribution to make in cancer therapy. Targeting TME with nanocarriers (NCs) has been widely used to directly deliver anticancer drugs to control TME, which has revealed auspicious outcomes. TME can be reprogrammed by using a range of NCs to regulate immunosuppressive factors and activate immunostimulatory cells. Moreover, TME can be ameliorated via regulating the redox environment, oxygen content, and pH value of the tumor site. NCs have the capacity to provide site-specific delivery of therapeutic agents, controlled release, enhanced solubility and stability, decreased toxicities, and enhanced pharmacokinetics as well as biodistribution. Numerous NCs have demonstrated their potential by inducing distinct anticancer mechanisms by delivering a range of anticancer drugs in various preclinical studies, including metal NCs, liposomal NCs, solid lipid NCs, micelles, nanoemulsions, polymer-based NCs, dendrimers, nanoclays, nanocrystals, and many more. Some of them have already received US Food and Drug Administration approval, and some have entered different clinical phases. However, there are several challenges in NC-mediated TME targeting, including scale-up of NC-based cancer therapy, rapid clearance of NCs by the mononuclear phagocyte system, and TME heterogeneity. In order to harness the full potential of NCs in tumor treatment, there are several factors that need to be carefully studied, including optimization of drug loading into NCs, NC-associated immunogenicity, and biocompatibility for the successful translation of NC-based anticancer therapies into clinical practice. In this review, a range of NCs and their applications in drug delivery to remodel TME for cancer therapy are extensively discussed. Moreover, findings from numerous preclinical and clinical studies with these NCs are also highlighted. Full article

This study aims to compare nanoemulsions and conventional emulsions as delivery systems for plant oils. For this reason, the formulation approach was evaluated, followed by an assessment of physicochemical properties and stability. Six different compositions of emulsions and their respective nanoemulsions were prepared using combinations of solid lipids (beeswax or cocoa butter) with liquid lipids (olive, almond, or apricot oil). Their physicochemical characteristics and their colloidal stability over time were assessed using Dynamic Light Scattering or Static Light Scattering. The performance of samples on the skin was assessed by measuring their occlusion effect (F), while their hydrating effect was assessed on healthy volunteers. The nanoemulsions exhibited improved stability compared to the corresponding conventional emulsions of the same composition. However, all samples (emulsions or nanoemulsions) exhibited a satisfactory occlusive effect (F > 10), mainly at 6 h. In addition, all samples caused increased skin hydration by 10–20% one hour post-application. Nanoemulsions containing plant-origin oils showed better physicochemical stability compared to their corresponding emulsions. The in vivo assessment revealed no skin irritation caused by the samples. Nevertheless, subjective evaluations by volunteers unveil a preference for conventional emulsions, which were perceived as providing a more favorable skin texture, regardless of their composition. Full article

The depletion of the ozone layer and climate change have increased exposure to ultraviolet (UV) radiation, driving the search for natural photoprotective agents. Marine macroalgae, particularly Gracilaria sp. (Rhodophyta) and Sargassum polyceratium (Ochrophyta), are rich in UV-absorbing bioactives, such as mycosporine-like amino acids (MAAs) and fucoxanthin, offering natural alternatives to synthetic sunscreens. This study aimed to develop and optimize a nanoemulsion incorporating both algal extracts, with MAAs and fucoxanthin strategically distributed in the aqueous and oil phases, respectively, to enhance synergistic broad-spectrum UV protection. MAAs were quantified in Gracilaria sp. using UHPLC-DAD, revealing 8.03 mg/g dry weight, primarily composed of shinorine and porphyra-334. Fucoxanthin was identified in S. polyceratium at 0.98 mg/g dry weight. A Box–Behnken design (BBD) was employed to optimize the nanoemulsion, targeting minimal droplet size and optimal ζ potential. The resulting formulation achieved a droplet size less than 100 nm and a ζ potential less than −25.0 mV. In vitro spectrophotometric analysis demonstrated significant photoprotective potential. The nanoemulsion containing only 375 ppm of algal extracts exhibited a UVA ratio of 1.25 and a critical wavelength of 379 nm, meeting the criteria for broad-spectrum protection and outperforming the commercial natural filter Helioguard^®365. These results confirm the efficacy of combining red and brown algae extracts in a nanoemulsion platform to deliver sustainable, low-dose photoprotection. This work presents, for the first time, the incorporation of red and brown algae extracts into a single nanoemulsion system, representing a novel strategy to maximize the combined photoprotective potential of MAAs and fucoxanthin. Ultimately, this investigation contributes to the growing field of marine-derived sunscreens and supports the advancement of “blue beauty” innovations aligned with eco-conscious formulation principles. Full article

Nanoemulsified corn oil was tested on twenty-one multiparous lactating Barki ewes (mean ± SD: 3 ± 0.4 parity, 44.3 ± 1.9 kg body weight, 30 ± 2.7 months of age, and 402 ± 23 g/d of prior milk production) randomly allocated to the following treatments (n = 7 ewes/group): Control—a basal diet consisting of 50% concentrate mixtures and 50% berseem clover; CO—the Control diet + 3% of corn oil; NCO—the Control diet + 3% of nanoemulsified corn oil. A completely randomized design of 25 days of adaptation and 5 days of sampling was employed with seven ewes per treatment. Despite feeding oil according to the recommended values, CO decreased the dry matter intake by 8.3% and 6.7% compared to the Control and NCO, respectively. The negative impact of CO extended to reducing the concentrations of ammonia and total volatile fatty acids in the rumen. On the other hand, NCO had less effect on the biohydrogenation intermediates profile compared to CO; noticeably, higher proportions of unsaturated fatty acid (UFA) were associated with NCO; these results were also supported by an increase in the rumen microbial population with NCO compared to CO, especially the biohydrogenation bacteria, which showed higher abundance with NCO despite the low presence of biohydrogenation intermediates. In conclusion, the NCO demonstrated the ability to decrease the transformation of unsaturated fatty acids into saturated fatty acids in the biohydrogenation environment. This effect was not associated with decreased dry matter intake, changes in nutrient digestibility, or alterations in fermentation patterns. Full article

Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and increased bioavailability of the drug. Methods: The levels of each factor(X) were established using a pseudo-ternary diagram, and the Box-Behnken design (BBD) was used to evaluate the components of oil (18.9 mg), surfactant (70.7 mg), and co-surfactant (10.0 mg) to optimize the SNEDDS formulation. The response(Y) considered were particle size, polydispersity index (PDI), transmittance, and stability. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to analyze the particle size and morphology. In vitro and ex vivo diffusion tests were conducted to assess drug flux and permeability. Result: Using a response optimization tool, the values of each X factor were optimized to achieve a small particle size (nm), a low polydispersity index (PDI), and high transmittance (%), resulting in a formulation prepared with 18.9 mg of oil, 70.7 mg of surfactant, and 10.0 mg of co-surfactant. The optimized SNEDDS exhibited a small particle size of 24.89 nm, a minimal PDI of 0.068, and a high transmittance of 74.85%. A transmission electron microscopy (TEM) analysis confirmed the presence of uniform spherical nanoemulsion droplets with an observed mean diameter of less than 25 nm, corroborating the dynamic light scattering (DLS) measurements. Furthermore, the SNEDDS demonstrated improved stability under the stress conditions of heating–cooling cycles, with no phase separation, creaming, or caking observed and no differences in its particle size, PDI, or transmittance. In vitro and ex vivo diffusion tests demonstrated that the flux of the optimized SNEDDS (2.723 ± 0.133 mg/cm², 5.446 ± 0.390 μg/cm²) was about 2.5 and 4 times higher than that of the drug dispersion, and the initial diffusion was faster, which is suitable for the characteristics of eye drops. Conclusions: Therefore, the formulation of a flurbiprofen-loaded SNEDDS (FLU-SNE) was successfully optimized using the QbD approach. The optimized FLU-SNE exhibited excellent stability and enhanced permeability, suggesting its potential effectiveness in treating various ocular inflammations, including uveitis and cystoid macular edema. Full article

A covalent complex of okra seed protein (OSP) and rutin was prepared using the alkali-induced method and characterized. Its application in nanoemulsions was also evaluated. Multi-spectral analysis confirmed the formation of the covalent complex, with OSP as the main body. With an increasing rutin dosage during the preparation process, the amount of rutin in the complex progressively ascended, and the α-helix structure and surface hydrophobicity of the complex gradually declined. The complex exhibited remarkable ABTS radical scavenging capacity and reducing power, which were proportional to the total phenolic content. The OSP/rutin complex could be utilized for the fabrication of O/W nanoemulsions, which remained stable in terms of droplet size and appearance after 28 days of storage at both 4 °C and 25 °C. Furthermore, lipid oxidation in the nanoemulsion stabilized by the OSP/rutin covalent complex could be effectively inhibited, and the emulsion could enhance the UV irradiation resistance of lutein loaded in the oil phase. Our results can provide a reference for the development of protein–polyphenol covalent complexes. Full article

Background/Objectives: Natural products are gaining increasing importance due to the large variety of biological activities exerted by their constituents. Among these, the products deriving from Acmella oleracea (L.) R.K. Jansen can be exploited for their local anaesthetic, myorelaxant, anti-inflammatory/analgesic, and antifungal properties. In this regard, there is a need to develop novel formulations for the topical delivery of A. oleracea-derived extracts to widen their use in the pharmaceutical and cosmetic fields. Methods: Nanoformulations, i.e., nanoemulsions (NEs) and microemulsions (MEs), were investigated as a strategy to encapsulate an extract from A. oleracea at the nanoscale level in water and then incorporated into xanthan gum-based hydrogels. Results: Only NEs provided a physically stable formulation, while the precipitation of solid hydrophobic components from the extract was observed during ME preparation under all tested conditions despite the use of ethyl oleate as an oily co-solvent. The optimized NE-based hydrogel remained physically stable over six months, as confirmed by rheological measurements and polarized optical microscope observation, without a phase separation phenomenon. Therefore, NEs resulted more suitable nanodispersed systems than MEs for the encapsulation of A. oleracea extract, which contains a large amount of hydrophobic constituents that are solid at room temperature. Furthermore, the sustained spilanthol release across an artificial membrane (Franz cell apparatus) and the cytotoxic profile on HaCaT cell line support its potential topical application. Conclusions: The outcomes of this study provided valuable insights into the formulation of A. oleracea extract, broadening its fields of applicability, including topical administration. Full article