Search Results (3,785)

Arthropod-borne orthoflaviviruses, including dengue, Zika, Japanese encephalitis, yellow fever and West Nile viruses, pose a significant global public health threat, causing hundreds of millions of infections annually with severe clinical symptoms. However, the lack of effective vaccines and antiviral drugs, coupled with the biosafety risks associated with handling live highly pathogenic strains, hinders progress in antiviral research. Pseudovirus technology, which uses single-round infectious viral particles lacking replication competence, has thus gained prominence as a safe and versatile tool for antiviral research. This review systematically summarizes the construction, optimization, and applications of orthoflavivirus pseudoviruses in antiviral research. The primary construction strategies of orthoflavivirus pseudoviruses rely on multi-plasmid co-transfection of viral replicons and structural protein expression vectors, leveraging the host cell secretory pathway to mimic natural viral assembly and maturation. The core applications of pseudovirus technology are highlighted, including high-throughput screening and detection of neutralizing antibodies, identification of antiviral drugs targeting viral entry or replication, and evaluation of vaccine immunogenicity. Despite these strengths, the approach still faces limitations, such as incomplete simulation of native viral structures and batch-to-batch titer variability, which may affect the physiological relevance of findings. In summary, orthoflavivirus pseudovirus technology has become an essential platform in both basic virology research and translational medicine, providing critical insights and tools in the ongoing fight against arthropod-borne orthoflaviviruses diseases. Full article

While drug-eluting cardiovascular devices, including drug-eluting stents and drug-coated balloons, have significantly reduced restenosis rates, they remain limited by delayed vascular healing, chronic inflammation, and late adverse events. These limitations reflect a fundamental mismatch between current device pharmacology, which relies on nonselective antiproliferative drugs, and the highly coordinated, cell-specific programs that orchestrate vascular repair. Extracellular vesicles (EVs), nanometer-scale membrane-bound particles secreted by virtually all cell types, provide a biologically evolved platform for intercellular communication and cargo delivery. In the cardiovascular system, EVs regulate endothelial regeneration, smooth muscle cell phenotype, extracellular matrix remodeling, and macrophage polarization through precisely orchestrated combinations of miRNA, proteins, and lipids. Here, we synthesize mechanistic insights into EV biogenesis, cargo selection, recruitment, and functional effects in vascular healing and inflammation and translate these into a formal framework for EV-inspired device engineering. We discuss how EV-based or EV-mimetic coatings can be designed to sense the local microenvironment, deliver encoded biological “instruction sets,” and function within ECM-mimetic scaffolds to couple local stent healing with systemic tissue repair. Finally, we outline the manufacturing, regulatory, and clinical trial issues that must be addressed for EV-inspired cardiovascular devices to transition from proof of concept to clinical reality. By shifting the focus from pharmacological suppression to biological regulation of healing, EV-based strategies offer a path to resolve the long-standing tradeoff between restenosis prevention and durable vascular healing. Full article

Background: 5-Azacytidine (5-Aza) is a clinically important DNMT inhibitor with the potential to modulate cardiac remodeling by epigenetically reprogramming human cardiac fibroblasts (HCFs). However, its clinical utility is limited by rapid hydrolytic degradation. Nanoparticle (NP) encapsulation offers a strategy to mitigate this instability. This study evaluated the physical and chemical stability of free 5-Aza and 5-Aza-loaded lipid nanoparticles (5-Aza-NP) under different storage temperatures and examined their effects on DNA methylation-related gene expression in HCFs. Methods: Hyaluronic acid-stabilized lipid NPs were prepared using a solvent displacement method. Particle size, polydispersity index (PDI), and zeta potential were monitored over four days at −20 °C, 4 °C, and 30 °C. Chemical stability was assessed using HPLC and first-order kinetic modeling. Functional activity was evaluated by treating HCFs with free 5-Aza or 5-Aza-NP stored for 96 h and measuring DNMT1, DNMT3A, and DNMT3B expression by RT-qPCR. Results: 5-Aza-NP remained physically stable at 4 °C, while −20 °C induced aggregation and 30 °C caused thermal variability. Free 5-Aza degraded rapidly at 30 °C (6.56% remaining at 72 h), whereas 5-Aza-NP preserved 11.54%. Kinetic modeling confirmed first-order degradation, with consistently longer half-lives for the NP formulation. Functionally, 5-Aza–NP preserved its ability to suppress DNMT1 expression following 96 h of storage at 4 °C, whereas free 5-Aza showed reduced activity. In contrast, DNMT3A and DNMT3B levels remained low and unchanged across all treatments. Conclusions: NP encapsulation enhances the physicochemical stability of 5-Aza and preserves its DNMT1-inhibitory activity, while DNMT3A/B remain unaffected. These findings support NP-based delivery as a promising strategy to stabilize labile epigenetic drugs such as 5-Aza. Full article

Background: Liposomes have been successfully used in clinics as an excellent drug delivery system. However, once they enter the body, they adsorb surrounding proteins and form a protein corona, which affects how liposomes behave in vivo. Therefore, controlling the formation of the protein corona is crucial for achieving effective treatment outcomes. Among the many variables affecting liposome protein corona formation, the composition of the liposomes themselves and the surrounding ionic environment are two particularly critical factors. Methods: In this context, this study selected bovine serum albumin as a model protein to investigate the influence and mechanism of physiologically relevant inorganic ions (magnesium chloride) and varying proportions of cationic lipid components (1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)) on protein adsorption behavior of liposomes. We evaluated characterization parameters, including particle size and zeta potential, and employed various spectroscopic techniques to elucidate the changes during the interaction between bovine serum albumin and liposomes. Results: The zeta potential results showed that liposomes without DOTAP exhibited a significantly negative potential (−45.20 ± 0.24 mV), while the zeta potential became increasingly positive with higher DOTAP proportions (+19.64 ± 0.39 mV and +51.03 ± 1.74 mV). Correspondingly, the amount of protein adsorption also increased with the rising DOTAP content. Furthermore, fluorescence spectroscopy indicated that the addition of either DOTAP or magnesium ions led to a decrease in both the K_sv and K_a parameters. Conclusions: Specific hypothetical models were advanced subsequently; per the varying proportion of DOTAP, we proposed an insertion or surface adsorption model, and further examined the influence of magnesium chloride on the interactions between the liposomes and proteins. We believe this study will provide a new research paradigm for the design and application of liposomes, laying a foundation for further in vivo investigations. Full article

Valsartan (Val)—a lipophilic non-peptide angiotensin II type 1 receptor antagonist—is highly effective against hypertension and displaying limited solubility in water (3.08 μg/mL), thereby resulting in low oral bioavailability (23%). The limited water solubility of antihypertensive drugs can pose a challenge, particularly for rapid and precise administration. Herein, we synthesize and characterize valsartan-containing silver nanoparticles (Val-AgNPs) using Mangifera indica leaf extracts. The physicochemical, structural, thermal, and pharmacological properties of these nano-conjugates were established through various analytical and structural tools. The spectral shifts in both UV-visible and FTIR analyses indicate a successful interaction between the valsartan molecule and the silver nanoparticles. The resulting nano-conjugates are spherical and within the size range of 30–60 nm as revealed in scanning electron-EDS and atomic force micrographs. The log-normal distribution of valsartan-loaded nanoparticles, with a size range of 30 to 60 nm and a mode of 54 nm, indicates a narrow, monodisperse, and highly uniform particle size distribution. This is a favorable characteristic for drug delivery systems, as it leads to enhanced bioavailability and a consistent performance. Dynamic Light Scattering (DLS) analysis of the Val-AgNPs indicates a polydisperse sample with a tendency toward aggregation, resulting in larger effective sizes in the suspension compared to individual nanoparticles. The accompanying decrease in zeta potential (to −19.5 mV) and conductivity further supports the idea that the surface chemistry and stability of the nanoparticles changed after conjugation. Differential scanning calorimetry (DSC) demonstrated the melting onset of the valsartan component at 113.99 °C. The size-dependent densification of the silver nanoparticles at 286.24 °C correspond to a size range of 40–60 nm, showing a significant melting point depression compared to bulk silver due to nanoscale effects. The shift in Rf for pure valsartan to Val-AgNPs suggests that the interaction with the AgNPs alters the compound’s overall polarity and/or its interaction with the stationary phase, complimented in HPTLC and HPLC analysis. The stability and offloading behavior of Val-AgNPs was observed at pH 6–10 and in 40% and 80% MeOH. In addition, Val-AgNPs did not reveal hemolysis or significant alterations in blood cell indices, confirming the safety of the nano-conjugates for biological application. In conclusion, these findings provide a comprehensive characterization of Val-AgNPs, highlighting their potential for improved drug delivery applications. Full article

Abdominal aortic aneurysm (AAA) is a life-threatening disease. Although AAA is generally asymptomatic, the mortality rate remains very high once rupture occurs, even with successful treatment. The pathophysiology of AAA involves inflammatory cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. However, there are various unclear aspects of pathophysiology due to cellular heterogeneity and multifactorial disease. Moreover, there are no blood biomarkers or available pharmacological drugs for AAA. Extracellular vesicles (EVs) are lipid bilayer particles released from every type of cell for intercellular communication. EVs include proteins, DNA, RNA (mRNA, microRNA), and lipids. EV cargos are delivered to recipient cells and modulate their biological effects. Although fewer studies have investigated EVs in AAA than in other cardiovascular diseases with similar molecular mechanisms, recent research indicates that EVs play a significant role in AAA development. Further research on EVs and AAA will contribute to the elucidation of AAA pathophysiology and the development of novel pharmacological drugs. In this review, we summarize the EV-associated pathophysiology, EV-based biomarkers, and EV-based treatment strategies in AAA. We also discuss the prospects for EVs research in AAA. Full article

Water-soluble poly-β-cyclodextrins (PCDs), crosslinked with ethylenediaminetetraacetic acid dianhydride (EDTADA), were synthesized at varying β-CD:EDTADA molar ratios (1:6, 1:9, 1:12, 1:15) to develop multifunctional nanocarriers with the ability to complex drugs, polymers, and ions. All PCDs exhibited nanometric particle sizes (14 to 28 nm), negative zeta potential (−18 to −27 mV), and adjustable content of free carboxyl groups controlled by crosslinker ratio. Functional evaluations demonstrated effective Ca²⁺ chelation and a linear inclusion complexation profile with acyclovir, but not with naproxen, highlighting pH-dependent solubility effects. Additionally, PCDs successfully formed polyelectrolyte complexes with poly-L-lysine, indicating their potential as components of advanced drug delivery systems. Among the analyzed variants, PCD 1:6 showed reduced yields, fewer reactive groups, and diminished ion-binding capacity compared to formulations with higher crosslinker content. These findings underscore the importance of crosslinking density in modulating physicochemical and functional properties and support the potential of EDTA-crosslinked PCDs as versatile platforms for advanced, ion-sensitive biomedical applications. Full article

Insomnia remains a widespread global health issue, and traditional hypnotic drugs often produce adverse effects. Although spinosin in Ziziphi Spinosae Semen has sleep-promoting effects, its use is limited by poor solubility and low oral bioavailability. In this study, the solvent melt method was used to prepare spinosin solid dispersions, optimising the process with an L₉(3⁴) orthogonal design based on apparent solubility. In vitro dissolution testing showed that solid dispersions of varying particle sizes dissolved more readily than pure spinosin, with smaller particles exhibiting faster dissolution. Cellular uptake was assessed in human colon adenocarcinoma cells, with results revealing enhanced uptake of smaller-particle solid dispersions. Powder X-ray diffraction confirmed that spinosin transformed from a crystalline to an amorphous state in the dispersion system. A quadratic orthogonal experiment was conducted to optimise functional dairy beverage formulation, using the centrifugal sedimentation rate as the evaluation index. In vivo experiments demonstrated that the resulting functional dairy beverage reduced spontaneous activity in mice, achieved a 60% sleep-onset rate, improved ethanol-induced memory impairment and produced marked sleep-promoting effects. Moreover, pharmacokinetic studies confirmed that the spinosin solid-dispersion-based functional dairy beverage significantly enhanced the systemic exposure and oral bioavailability of spinosin compared to the spinosin water suspension. These findings indicate that solid dispersion technology effectively enhances spinosin solubility and that the developed functional dairy beverage shows promise as a sleep-promoting functional food. Full article

Polyelectrolyte microspheres based on a polymer containing sulfonate groups are considered promising drug delivery systems for encapsulating drugs and ensuring their prolonged release. In this study, gel microparticles based on various sulfonate-containing polymers were formed, and their potential as drug delivery systems was evaluated, particularly for the controlled administration of the cytotoxic anthracycline antibiotic doxorubicin and the antifungal drug fuchsine. An undeniable advantage of such gel microspheres is the presence in their structure of sulfonate groups localized both in the surface layer and in the volume. The main monomers used were styrene-4-sulfonic acid sodium salt and 3-sulfopropyl methacrylate potassium salt; spherical, porous microparticles were obtained via free-radical reverse suspension polymerization. Microsphere properties (size, porosity, pore structure, electrical surface properties, and swelling) were tailored by changing the nature of the sulfonate, using a comonomer (vinyl acetate or ethyl acrylate), adding a co-solvent, or modulating the crosslinker composition, which influenced drug loading efficiency (doxorubicin, fuchsine). The gel-like structure of the microspheres was confirmed, and the sulfonate groups were found to be distributed throughout both the surface layer and the internal volume of the microspheres. A comparison was also made with non-porous polymer particles containing sulfonate groups. The sorption capacity of the gel microspheres for doxorubicin was 2.2 mmol/g, significantly higher than the 0.4 mmol/g observed for the non-porous reference particles. The obtained values of doxorubicin sorption on gel microspheres are over 60 times higher than the values reported in the literature. Full article

Background: Nebulized polymyxin B (PMB) therapy is widely used in intensive care units for treating hospital-acquired and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria, yet its pulmonary delivery performance during invasive mechanical ventilation remains poorly characterized. Methods: An in vitro adult mechanical ventilation model was used. We evaluated two nebulizers (vibrating mesh nebulizer [VMN] and jet nebulizer [JN]) at three positions (standalone nebulizer, 15 cm from the Y-piece, and the humidifier’s dry end) with two artificial airway types (endotracheal and tracheostomy tubes). Lung deposition was predicted using the multiple-path particle dosimetry model, incorporating the Yeh/Schum five-lobe adult lung model. Results: In the standalone setup, the percentage of delivered dose of VMN and JN was approximately 40% and 34%, respectively. Mechanical ventilation significantly reduced the delivered dose (all p ≤ 0.0085), with VMN at the humidifier’s dry end delivering only 2.14–2.99% of the nominal dose. In all the tested ventilation scenarios, both the use of the JN and positioning the nebulizer 15 cm from the Y-piece significantly increased aerosol delivery (all p ≤ 0.021). While the ventilator circuit reduced the total drug amount, it filtered larger aerosols. This resulted in a smaller mass median aerodynamic diameter and a higher fine particle fraction (all p < 0.0001), which doubled the predicted alveolar deposition fraction (from 13–14% in standalone to 23–28% in ventilation scenarios) and eliminated extrathoracic deposition. Conclusions: This study provides the first in vitro and in silico assessment of PMB aerosol delivery during invasive mechanical ventilation. Nebulizer type, its placement within the circuit, and the artificial airway are critical factors that significantly alter the pulmonary delivery of PMB aerosol and subsequently impact its lung deposition. Full article

Background: Lewisite, a potent chemical warfare agent, induces rapid and progressive cutaneous damage, necessitating treatment strategies that offer both immediate decontamination and prolonged therapeutic action. This study aimed to develop and evaluate a composite topical formulation comprising 4-phenylbutyric acid (4-PBA)-loaded emulsomes embedded within a foam vehicle to address both aspects of vesicant-induced skin injury intervention. Methods: Emulsomes composed of a stearic acid–cholesterol solid lipid core stabilized by a lecithin shell were prepared via thin film hydration and optimized by varying lipid ratios and drug loading parameters. Formulations were characterized for drug loading, particle size, and zeta potential. Physicochemical compatibility was assessed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses. Stability was evaluated under accelerated refrigerated (25 °C/60% RH) and room temperature (40 °C/75% RH) conditions. The optimized formulation was incorporated into a foam base and evaluated for decontamination efficiency, drug release kinetics, in vitro permeation, and in vivo efficacy. Results: The selected formulation (E2) exhibited high drug loading (17.01 ± 0.00%), monodisperse particle size (PDI = 0.3 ± 0.07), and stable zeta potential (−40 ± 1.24 mV). FTIR and DSC confirmed successful encapsulation with amorphous drug dispersion. The emulsome-foam demonstrated dual functionality: enhanced decontamination (66.84 ± 1.27%) and sustained release (~30% over 24 h), fitting a Korsmeyer–Peppas model. In vitro permeation showed significantly lower 4-PBA delivery from E2 versus free drug, confirming sustained release, while in vivo studies demonstrated therapeutic efficacy. Conclusions: This emulsome-foam system offers a promising platform for topical treatment of vesicant-induced skin injury by enabling both immediate detoxification and prolonged anti-inflammatory drug delivery. Full article

Background and Objectives: Implant-associated complications, including foreign-body responses and infection risk, remain major concerns in reconstructive and aesthetic breast surgery. Antimicrobial polymer coatings have been proposed as potential preventive strategies, but early-stage development requires simple and ethically refined in vivo models. This pilot study aimed to (i) establish a practical workflow for applying PLGA–vancomycin coatings onto PTFE substrates used as experimental analogs for smooth silicone implants, and (ii) develop a small-animal implantation protocol for short-term evaluation of surgical feasibility and local tissue tolerability. Materials and Methods: PLGA microparticles and PLGA–vancomycin microparticles were prepared using a double-emulsion solvent-evaporation method and applied onto PTFE discs. Particle size and polydispersity were assessed based on dynamic light scattering (DLS), and surface charge was measured via zeta potential. A bilateral subcutaneous implantation model was used in four Wistar rats, each receiving a PTFE disc coated with PLGA-only on one side and a disc coated with PLGA–vancomycin on the other. Animals were monitored for postoperative recovery, wound appearance, and general condition. After four weeks, implants and surrounding tissues were harvested for macroscopic and preliminary histological evaluation. Results: Both PLGA-only and PLGA–vancomycin microparticles showed submicron mean hydrodynamic diameters and moderately polydisperse distributions typical for double-emulsion formulations. All animals recovered normally, maintained stable body weight, and exhibited no macroscopic signs of adverse reactions. Preliminary histology showed early fibrous capsule formation with mild inflammatory infiltrate around both types of coated implants, without qualitative differences observed in this pilot setting. Conclusions: This preliminary study demonstrates the feasibility of applying PLGA-only and PLGA–vancomycin coatings onto PTFE implant analogs and establishes a reproducible, minimal-use rat model for short-term evaluation of local tissue tolerability. The protocol provides a practical foundation for future work on coating stability, drug-release kinetics, antibacterial activity, and long-term tissue responses on medical-grade silicone substrates. Full article

Background/Objectives: Extracellular vesicles (EVs) are nanosized carriers with high biocompatibility, low immunogenicity, and the ability to cross biological barriers, making them attractive for drug delivery. Despite growing interest, the clinical translation of drug-loaded EVs remains limited. This systematic review aimed to summarize current evidence on EV sources, loading strategies, therapeutic applications, and translational challenges. Methods: Following PRISMA 2020 guidelines, a systematic search was conducted in Embase, PubMed, Reaxys, and Scopus for the period 2020–2025. Eligible studies included original articles on drug-loaded EVs from human, animal, plant, or other sources. Data on EV source, drug type, particle size, loading method, administration route, and therapeutic application were extracted. Clinical trials were identified through ClinicalTrials.gov. Results: A total of 65 studies were included after screening 5316 records, along with two clinical trials. Human mesenchymal stem cell (MSC)-derived EVs were the most frequent source in oncology, while plant-derived EVs predominated in non-oncology applications. Anti-cancer drugs such as doxorubicin, gemcitabine, and docetaxel were most frequently loaded, alongside curcumin, berberine, and atorvastatin. EV sizes generally ranged from 50 to 200 nm, with larger vesicles reported for plant-derived EVs. Intravenous administration predominated, with most studies demonstrating sustained release and enhanced therapeutic efficacy. Passive loading was most common, especially for hydrophobic drugs, whereas active methods such as electroporation and sonication were preferred for hydrophilic cargo. Two clinical trials showed preliminary therapeutic benefits with favorable safety. Conclusions: Drug-loaded EVs represent a promising and versatile drug delivery platform, yet their clinical translation is hindered by variability in isolation and loading methods, production scalability, and safety evaluation. Further standardization and large-scale studies are needed to advance EV-based therapeutics toward clinical use. Full article

Alginate [ALG] and chitosan [CS] are biomaterials of importance in drug-delivery because of their ability to form ionically-crosslinked nanosystems and polyelectrolyte-complexes under mild conditions. Here, a modified ionic-polyelectrolyte-pre-gelation method, with a controlled addition of reagents and sonication throughout the process, is reported to produce ALG¬¬-CS-based NPs. A mathematical study of the effects of the factors with influence in the process on the properties of NPs has been performed using a two-phase-design-of-experiment-based procedure, something never done to our knowledge. The concentration of ALG, CS and CaCl₂ and the ratio ALG:CS have significant influence on polydispersity (PDI), surface-charge (ZP) and encapsulation efficiency (EE%) of NPs. Moreover, CS flow rate has a significant effect over PDI and EE%. Thus, the values of ALG, CS and CaCl₂ concentration (mg/mL), ALG:CS (mL:mL) and CS flow rate (mL/min) to obtain the minimum-expected PDI (0.168) or the optimized EE% (86.7) are {0.30, 0.79, 1.00, 2.50:1.00, 0.86} or {0.30, 1.00, 1.00, 2.50:1.00, 2.00}, with ALG:CaCl₂ (mL:mL) and CaCl₂ flow rate (mL/min) fixed at 2.50:0.31 and 1.25. Although most of the conditions yielded highly-negative particles (minimum-expected of −67.8 mV using 0.69, 0.30 and 0.13 mg/mL of ALG, CS and CaCl₂ and ALG:CS of 2.50:0.59 mL:mL), varying the mass ratio of ALG:CS allowed for the generation of positively-charged particles (up to +21.1 mV with 0.30, 1.00 and 0.61 mg/mL of ALG, CS and CaCl₂ and ALG:CS of 2.50:1.00 mL:mL). In both cases, ALG:CaCl₂ (mL:mL), CaCl₂ and CS flow rates (mL/min) were fixed at 2.50:0.31, 1.25 and 1.25. The model for the NPs size depends only on CS and CaCl₂ concentrations, with the minimum- or maximum-expected (160 or 635 nm) at 0.30 and 1.00 or 1.00 and 0.30 of CS and CaCl₂, although the method allows a wide range of sizes (144.0–1965.0 nm). Full article

Background/Objectives: The poor aqueous solubility of many therapeutic compounds remains a key barrier to achieving optimal oral bioavailability. While traditional formulation strategies—such as surfactant-based solubilization, nanocrystals, and amorphous solid dispersions—have yielded varying degrees of success, they are often limited by poor physical stability, high excipient loads, inconsistent absorption, and safety concerns associated with long-term surfactant exposure. To address these challenges, this review evaluates surfactant–particle hybrid drug delivery systems as a next-generation platform for enhancing the oral delivery of poorly water-soluble drugs. Methods: A comprehensive literature analysis was conducted to examine the mechanistic foundations, formulation techniques, and translational hurdles associated with these hybrid systems. Representative in vitro and in vivo case studies were critically reviewed to assess performance consistency, particularly with respect to dissolution enhancement, supersaturation stabilization, and permeability modulation. Consideration was also given to manufacturing feasibility, excipient safety, scalability, and regulatory constraints. Results: Findings indicate that surfactant–particle hybrids provide synergistic benefits by integrating solubilization and stabilization functions with tailored particle design. These systems have shown consistent improvements in pharmacokinetic profiles and drug absorption across diverse drug candidates. However, limitations remain, including challenges in long-term physical stability and excipient compatibility that must be addressed for broader application. Conclusions: Surfactant–particle hybrid systems offer a versatile and promising approach to overcoming the limitations of poorly soluble drugs. With careful attention to formulation optimization and regulatory compliance, they have the potential to serve as a transformative platform in future oral drug delivery strategies. Full article