Search Results (559)

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Oral delivery of hydrophobic compounds remains challenging due to their poor aqueous solubility and the potential toxicity associated with conventional surfactant-based emulsions. To address these issues, we present a surfactant-free encapsulation strategy using electrosprayed alginate hydrogel beads for the stable and controlled delivery of hydrophobic oils. Hydrophobic compounds were dispersed in high-viscosity alginate solutions without surfactants via ultrasonication, forming kinetically stable oil-in-water dispersions. These mixtures were electrosprayed into calcium chloride baths, yielding monodisperse hydrogel beads. Higher alginate concentrations improved droplet sphericity and suppressed phase separation by enhancing matrix viscosity. The resulting beads exhibited stimuli-responsive degradation and controlled release behavior in response to physiological ionic strength. Dense alginate networks delayed ion exchange and prolonged structural integrity, while elevated external ionic conditions triggered rapid disintegration and immediate payload release. This simple and scalable system offers a biocompatible platform for the oral delivery of lipophilic active compounds without the need for surfactants or complex fabrication steps. Full article

Background/Objectives: Mammary carcinoma is a common disease in female dogs. Cannabidiol (CBD) can inhibit cell proliferation and induce apoptosis in human cancer cells. However, its low solubility in aqueous media requires solvents such as ethanol or dimethylsulfoxide that limit their dosage. Incorporating CBD into oil-in-water nanoemulsions (Nem) can improve its aqueous dispersibility. This study aimed to develop a CBD-Nem formulation and evaluate its effects on canine mammary cancer cell lines (CF41.Mg and IPC366) and non-cancer cells (MDCK). Methods: CBD-Nem was prepared with Miglyol 812 oil and Epikuron 145 V as the surfactant, and was characterized by analyzing size, morphology, zeta potential, release profile, and uptake/internalization. Moreover, the antitumor effects of CBD-Nem were evaluated in cancer cells through viability, proliferation, cell cycle, and migration–invasion assays. Results: CBD-Nem exhibited a monodisperse nanometric population (~150 nm), spherical shape, and negative zeta potential (~−50 mV). The in vitro release kinetics showed slow and sustained delivery at both pH 5.5 and pH 7.4. Rhodamine-Nem, as a fluorescent model of CBD-Nem, was taken up and homogenously internalized in CF41.Mg cells. CBD-Nem decreased the viability of cancer cells with a maximum effect at 50 µM and showed a lower toxicity in MDCK cells. Long-term efficacy (20 days) was evidenced by CBD-Nem at inhibiting colony formation in cancer cells. Furthermore, CBD-Nem reduced the proportion of cells in the G2-M phase, induced apoptosis, and inhibited the migration and invasion of CF41.Mg cells. Conclusions: CBD-Nem exhibited an in vitro antitumor effect, which supports its study in dogs with mammary carcinoma. Full article

Surfactants are widely utilized in agriculture as emulsifying, dispersing, anti-foaming, and wetting agents. In these adjuvant roles, the inherent biological activity of the surfactant is secondary to the active ingredients. Here, the hydrophilic non-ionic surface-active tri-block copolymer Pluronic^® F68 is investigated for direct biological activity in wheat. F68 binds to and inserts into lipid membranes, which may benefit crops under abiotic stress. F68’s interactions with Triticum aestivum (var Juniper) seedlings and a seed-borne Bacillus spp. endophyte are presented. At concentrations below 10 g/L, F68-primed wheat seeds exhibited unchanged emergence. Root-applied fluorescein-F68 (fF68) was internalized in root epidermal cells and concentrated in highly mobile endosomes. The potential benefit of F68 in droughted wheat was examined and contrasted with wheat treated with the osmolyte, glycine betaine (GB). Photosystem II activity of droughted plants dropped significantly below non-droughted controls, and no clear benefit of F68 (or GB) during drought or rehydration was observed. However, F68-treated wheat exhibited increased transpiration values (for watered plants only) and enhanced shoot dry mass (for watered and droughted plants), not observed for GB-treated or untreated plants. The release of seed-borne bacterial endophytes into the spermosphere of germinating seeds was not affected by F68 (for F68-primed seeds as well as F68 applied to roots), and the planktonic growth of a purified Bacillus spp. seed endophyte was not reduced by F68 applied below the critical micelle concentration. These studies demonstrated that F68 entered wheat root cells, concentrated in endosomes involved in transport, significantly promoted shoot growth, and showed no adverse effects to plant-associated bacteria. Full article

Background/Objectives: 5-Fluorouracil (5-FU) and Irinotecan (IRT) are two of the most used chemotherapeutic agents in CRC treatment. However, achieving treatment goals has been hampered by poor drug delivery to tumor sites and associated toxicity from off-target binding to healthy cells. Though the synergism of 5-FU-IRT has provided incremental improvements in clinical outcomes, the short elimination half-life and off-target binding to healthy cells remain significant challenges. We postulated that nanoencapsulation of a combination of 5-FU and IRT in niosomes would prolong the drugs’ half-lives, while over-encapsulation lyophilized powder in Targit^® oral capsules would passively the CRC microenvironment and avoid extensive systemic distribution. Methods: Ranges of formulation and process variables were input into design of experiment (DOE Fusion One) software, to generate screening experiments. Niosomes were prepared using the thin-film hydration method and characterized by size, the polydispersity index (PDI), morphology and intrastructure, and drug loading. Blank niosomes ranged in size from 215 nm to 257 nm. Results: After loading with the 5-FU-IRT combination, the niosomes averaged 251 ± 2.20 nm with a mean PDI of 0.293 ± 0.01. The surfactant-to-cholesterol ratio significantly influenced the niosome size and the PDI. The hydrophilic 5-FU exhibited superior loading compared to the lipophilic IRT molecules, which probably competed with other lipophilic niosome components in niosomes’ palisade layers. In vitro dissolution in biorelevant media showed delayed release until lower intestinal region (IRT) or colonic region (5-FU). Conclusions: Thus, co-nanoencapsulation of 5-FU/IRT in niosomes, lyophilization, and over-encapsulation of powder in colon-specific capsules could passively target the CRC cells in the colonic microenvironment. Full article

Essential oils (EOs) represent natural bioactive agents with broad applications; however, their industrial utilization is often hampered by inherent volatility and instability, which current encapsulation methods struggle to overcome due to limitations such as reliance on synthetic surfactants. Proteins, owing to their amphiphilic nature, serve as materials for EOs microencapsulation, particularly when chemically modified. Building upon our previous work demonstrating improved emulsifying properties of hemp seed protein isolate (HPI) through covalent modification with gallic acid (GA), this study investigated its efficacy for essential oil encapsulation. This study developed a novel microencapsulation system utilizing conjugates of HPI and GA for stabilizing six essential oils (lemon, grapefruit, camellia, fragrans, oregano, and mustard). The microcapsules exhibited encapsulation efficiencies (EE) ranging from 40% to 88%, with oregano oil demonstrating superior performance due to carvacrol’s amphiphilic surfactant properties. Advanced characterization techniques revealed that high-EE microcapsules displayed compact morphologies, enhanced thermal stability, and reduced surface oil localization. Release kinetics followed either the Peppas or Weibull model, with oregano microcapsules achieving sustained release via matrix erosion mechanisms. Antioxidant assays and antimicrobial tests demonstrated multifunctional efficacy, where oregano microcapsules exhibited the highest radical scavenging and antimicrobial activity. These findings establish HPI-GA conjugates as unique dual-functional emulsifier-encapsulants, offering a sustainable and effective platform to enhance EO stability and bioactivity, particularly for applications in food preservation and pharmaceutical formulations. Full article

Breast cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Its treatment is complicated by molecular heterogeneity and the frequent development of multidrug resistance (MDR). Conventional drug delivery approaches are often limited by poor aqueous solubility, rapid systemic clearance, non-specific biodistribution, and off-target toxicity. This review will critically explore the possibility of surfactant-based drug delivery systems (DDSs) in addressing the constraints of standard breast cancer treatments. It focuses on the mechanisms by which surfactants promote solubility, facilitate cellular uptake, and overcome drug resistance, while also analyzing current therapeutic success and future directions. A thorough review of preclinical and clinical investigations was undertaken, focusing on important surfactant-based DDSs such as polymeric micelles, nanoemulsions, liposomes, and self-emulsifying systems (SEDDSs). Mechanistic insights into surfactant functions, such as membrane permeabilization and efflux pump inhibition, were studied alongside delivery systems incorporating ligands and co-loaded medicines. Pluronic^® micelles, TPGS-based systems, biosurfactant-stabilized nanoparticles, and lipid-based carrier surfactant platforms improve medication solubility, stability, and delivery. Genexol^® are examples of formulations demonstrating effective use and FDA translational potential. These systems now incorporate stimuli-responsive release mechanisms—such as pH, temperature, redox, immuno- and photodynamic treatment—artificial intelligence treatment design, and tailored treatment advancement, and responsive tailoring. Surfactant-enabled DDSs can improve breast cancer care. Innovative approaches for personalized oncology treatment are countered by the enduring challenges of toxicity, regulatory hurdles, and diminished scalability. Full article

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

Background/Objectives: Cutaneous melanoma is a potent neoplasm whose advancement is linked to catecholamine-induced angiogenesis through β-adrenergic receptors. Propranolol (PROP), a non-selective β-blocker, holds potential in oncology, but its systemic side effects restrict its viability. This study aims to nanoencapsulate PROP in Eudragit RL^®100 polymeric nanocapsules for topical melanoma treatment. Methods: Nanocapsules were created through interfacial deposition of preformed polymer and characterized in terms of particle size, zeta potential, pH, drug content, and encapsulation efficiency. In vitro evaluations include release profile, antioxidant activity, bioadhesiveness, hemolysis, cytotoxicity, and antitumor effect on melanoma cells. Additionally, migration assays were conducted. Results: The nanocapsules displayed an acidic pH, an average size of 151 nm, and a positive zeta potential. An encapsulation efficiency of 81% was achieved, even with the hydrochloride form of the drug. The release profile exhibited sustained release of PROP, showcasing enhanced antioxidant activity in the nanoencapsulated form. The formulations also exhibited significant bioadhesion with mucin and an in vitro hemolysis rate over 50%, attributed to the cationic polymer and surfactants present. Moreover, in the cell viability assays, the NC-PROP formulations significantly reduced melanoma cell viability. In the migration assay, both the nanocapsules with and without the drug significantly inhibited cell migration, supporting the potential therapeutic benefits of these formulations. Conclusions: The nanoencapsulation of PROP in Eudragit RL^®100 presents a viable strategy for topical treatment of cutaneous melanoma, enhancing release duration and reducing systemic effects. The assessments indicated distinct physical properties and substantial therapeutic potential. 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

In this review work, the different routes and methods for preparing hybrid materials based on nanostructured block copolymers (BCPs) and magnetic nanoparticles (MNPs) are analyzed, as they can be potentially employed in different sectors like biomedicine, electronic or optoelectronic devices, data storing devices, etc. The first procedure for their preparation consists of the nanostructuring of BCPs in the presence of previously synthesized NPs by modifying their surface for increasing compatibility with the matrix or employing magnetic fields for NP orientation, which can also promote the orientation of nanodomains. Surface modification with surfactants led to the selective confinement of NPs depending on the interaction (mainly hydrogen bonding) degree and their intensity. Surface modification with brushes can be performed by three methods, including grafting from, grafting to, or grafting through. Those methods are compared in terms of success for the positioning and confinement of NPs in the desired domains, showing the crucial importance of brush length and grafting density, as well as of NP amount and modification degree in the self-assembled morphology. Regarding the use of external magnetic fields, the importance of relative amounts of MNPs and BCPs employed and that of the magnetic field intensity for the orientation of the NPs and the nearby BCP domains is shown. The second procedure, consisting of the in situ synthesis of NPs inside the nanodomains by a reduction in the respective metallic ions or employing metal-containing BCPs for the generation of MNP patterns or arrays, is also shown. In all cases, the transference of magnetic properties to the nanocomposite was successful. Finally, a brief summary of some aspects about the use of BCPs for the synthesis, encapsulation, and release of MNPs is shown, as they present potential biomedical applications such as cancer treatment, among others. Full article

Background/Objectives: Raynaud’s phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers and toes to cold or stress. Oral therapy with tadalafil (TDL), a phosphodiesterase-5 inhibitor, is limited by systemic side effects and reduced patient compliance. This study aimed to develop and evaluate a TDL-loaded nanoemulgel for transdermal delivery as a non-invasive treatment alternative for cold-induced vasoconstriction. Methods: TDL-loaded nanoemulsions were prepared using the aqueous titration method with cinnamon oil as the oil phase and Cremophor RH40 and Transcutol as the surfactant–cosurfactant system. The optimized nanoemulsion was incorporated into a carbopol-based gel to form a nanoemulgel. The formulation was characterized for droplet size, morphology, thermodynamic stability, rheological properties, in vitro drug release, skin permeation, and pharmacokinetic behavior. Infrared thermography was employed to assess in vivo efficacy in cold-induced vasoconstriction models. Results: The optimized TDL nanoemulsion exhibited a spherical morphology, a nanoscale droplet size, and an enhanced transdermal flux. The resulting nanoemulgel displayed suitable physicochemical and rheological properties for topical application, a short lag time (0.7 h), and a high permeability coefficient (Kp = 3.59 × 10⁻² cm/h). Thermal imaging showed significant vasodilation comparable to standard 0.2% nitroglycerin ointment. Pharmacokinetic studies indicated improved transdermal absorption with a higher C_max (2.13 µg/mL), a prolonged half-life (t_1/2 = 16.12 h), and an increased AUC_0–24 compared to an oral nanosuspension (p < 0.001). Conclusions: The developed TDL nanoemulgel demonstrated effective transdermal delivery and significant potential as a patient-friendly therapeutic approach for Raynaud’s phenomenon, offering an alternative to conventional oral therapy. Full article

Linear anionic surfactants (LAS) pose significant stress to microbial denitrification in wastewater treatment. This study investigated the performance and adaptation mechanisms of heterotrophic nitrification-aerobic denitrification (HN-AD) microbial consortia under LAS exposure after short-term (SCM, 2 months) and long-term (LCM, 6 months) acclimation. Results showed a dose-dependent inhibition of total nitrogen (TN) removal, with LCM achieving 97.40% TN removal under 300 mg/L LAS, which was 16.89% higher than SCM. Biochemical assays indicated that LCM exhibited lower reactive oxygen species (ROS) levels, a higher ATP content, and reduced LDH release, suggesting enhanced oxidative stress resistance and membrane stability. EPS secretion also increased in LCM, contributing to environmental tolerance. Metagenomic analysis revealed that long-term acclimation enriched key genera including Pseudomonas, Aeromonas, and Stutzerimonas, which maintained higher expression of denitrification (e.g., nosZ, nirS) and ammonium assimilation genes (glnA, gltB). Although high LAS concentrations reduced overall community diversity and led to convergence between SCM and LCM structures, LCM retained greater functional capacity and stress resistance. These findings underscore the importance of acclimation in sustaining denitrification performance under surfactant pressure and offer valuable insights for engineering robust microbial consortia in complex wastewater environments. Full article

Background/Objectives: The usefulness of presepsin, which is released from macrophages, in acute exacerbation of interstitial lung diseases (AE-ILDs) is unknown. We aimed to investigate the utility of monitoring presepsin with other AE-ILD markers before and after steroid pulse therapy in AE-ILDs. Methods: This pilot single-center retrospective observational study involved 16 patients with AE-ILDs, including the AE of idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia and rapidly progressive connective tissue disease-associated ILD. Patients who survived 90 days were assigned to the survival group (n = 9). The remaining patients were classified in the non-survivor group (n = 7). To evaluate the therapeutic efficacy of steroid pulse therapy, specific serum markers were selected—presepsin, as a novel AE-ILD marker, and surfactant protein D, C-reactive protein, and lactate dehydrogenase (LDH), as classical AE-ILD markers. Results: Thirteen out of sixteen patients with AE-ILDs showed high presepsin levels (presepsin ≥ 470 pg/mL) before steroid pulse therapy. The post-/pre-presepsin ratio and the post-/pre-LDH ratio, calculated by dividing the presepsin and LDH levels after therapy by the levels before therapy, respectively, showed a positive correlation (r = 0.579, p = 0.021). As a result of this correlation, the post-/pre-presepsin–LDH index was created, obtained from the “post-/pre-presepsin ratio” multiplied by the “post-/pre-LDH ratio”. In a receiver operating characteristic curve analysis for non-survival, the post-/pre-presepsin–LDH index showed good discrimination as a prognostic marker for a poor outcome (AUC: 0.873, 95% confidence interval: 0.655–0.999). Conclusions: Tracking presepsin and LDH simultaneously may be useful for determining treatment response to steroid pulse therapy in the clinical management of AE-ILDs. Full article

Background: Celastrol (Cela), a phytochemical extracted from Tripterygium wilfordii, has been extensively investigated for its potential anti-inflammatory, anti-psoriatic, antioxidant, neuroprotective, and antineoplastic properties. However, its clinical translation is limited due to poor bioavailability, low solubility, and nonspecific toxicity. This study aimed to develop and evaluate an inhalable Cela-loaded nanoemulsion (NE) formulation to enhance targeted drug delivery and therapeutic efficacy in non-small cell lung cancer (NSCLC). Methods: The NE formulation was optimized using Capmul MCM (25%), Tween 80 (20%), Transcutol HP (5%), and water (50%) as the oil, surfactant, co-surfactant, and aqueous phase, respectively. Physicochemical characterization included globule size, zeta potential, and drug release in simulated lung fluid. In vitro aerosolization performance, cytotoxicity in NSCLC cell lines (A549), scratch and clonogenic assays, and 3D tumor spheroid models were employed to assess therapeutic potential. Results: The NE showed a globule size of 201.4 ± 3.7 nm and a zeta potential of −15.7 ± 0.2 mV. Drug release was sustained, with 20.4 ± 5.5%, 29.1 ± 10%, 64.6 ± 4.1%, and 88.1 ± 5.2% released at 24, 48, 72, and 120 h, respectively. In vitro aerosolization studies indicated a median aerodynamic particle size of 4.8 ± 0.2 μm, confirming its respirability in the lung. Cell culture studies indicated higher toxicity of NE-Cela in NSCLC cells. NE-Cela significantly reduced A549 cell viability, showing a ~6-fold decrease in IC₅₀ (0.2 ± 0.1 μM) compared to Cela alone (1.2 ± 0.2 μM). Migration and clonogenic assays demonstrated reduced cell proliferation, and 3D spheroid models supported its therapeutic activity in tumor-like environments. Conclusions: The inhalable NE-Cela formulation improved Cela’s physicochemical limitations and demonstrated enhanced anti-cancer efficacy in NSCLC models. These findings support its potential as a targeted, well-tolerated therapeutic option for lung cancer treatment. Full article