Search Results (461)

Fungal infections represent an escalating global health challenge due to their increasing incidence, the emergence of multidrug-resistant pathogens, and the limited development of new antifungal agents. Therapeutic efficacy is compromised by mutations in drug targets, overexpression of efflux pumps, alterations in the ergosterol biosynthetic pathway, biofilm-associated tolerance, and extensive genomic plasticity. The growing prevalence of antifungal resistance and the limited availability of effective therapeutic options highlight the urgent need to strengthen epidemiological surveillance and accelerate research into innovative therapeutic strategies. In this review, we discuss the potential of lipid-based drug delivery systems (LDDSs) as a versatile strategy to optimize antifungal administration and overcome resistance mechanisms. Liposomes (LPs), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoparticles (LNPs) offer high biocompatibility, efficient encapsulation of hydrophobic compounds, structural stability, and controlled drug release. Their nanoscale properties facilitate penetration into biofilms, promote intracellular uptake, and reduce the impact of efflux-mediated drug extrusion, thereby improving cellular penetration and circumventing resistance pathways. In addition, LDDSs increase bioavailability, reduce toxicity, and promote drug accumulation within poorly accessible tissue compartments. Overall, LDDSs represent a promising approach to expand the therapeutic arsenal against both superficial and invasive fungal infections, particularly those caused by multidrug-resistant pathogens. Full article

Nanostructured lipid carriers (NLCs) are colloidal delivery systems developed to address the low stability and limited bioavailability of sensitive active compounds. In this study, anthocyanin-rich barberry extract-loaded NLCs were prepared by a water-in-oil-in-water double emulsion method, using beeswax as the solid lipid and coriander essential oil as the liquid lipid. A combined D-optimal mixture design was employed to evaluate the effect of surfactant ratios (Tween 80/Tween 20 and polyglycerol ester (PGE)/polyglycerol polyricinoleate (PGPR)) on particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. The optimized formulation suggested by Design-Expert^® software was obtained at 90/10 Tween 80/Tween 20 and 90/10 PGE/PGPR ratios and showed a particle size of 94.25 nm, PDI of 0.18, zeta potential of −23.4 mV, and encapsulation efficiency of 74%. The experimental values were in close agreement with the predicted responses. TEM observations indicated spherical morphology at the nanoscale, while FTIR, DSC, and XRD analyses confirmed successful incorporation of barberry extract into the lipid matrix and a less ordered crystalline structure. During one month of storage, the optimized NLC was more stable at 4 °C compared with 25 °C and showed higher antioxidant activity than the free extract. It also exhibited a higher inhibitory effect against S. aureus and E. coli than the free form in MIC and MBC assays. Overall, the developed NLCs could serve as an effective carrier system to improve the stability of anthocyanin-rich barberry extract and extend its application in food formulations. Full article

Skin wound healing involves a delicate balance between proliferation and remodelling processes, with significant therapeutic challenges. The present work aimed to investigate the capacity of hybrid lipid nanocarriers carrying a complex phytochemical profile (HA-NLC-ArnicaM and/or RuscusA extracts) to counteract the destructive action of oxidative free radicals and to accelerate wound closure induced on BJ fibroblast cells. The lipid and hybrid nanocarriers have main diameters ranging from 145 nm to 180 nm, electrokinetic potential between −45 mV and −62 mV, and entrapment efficiency of plant extracts exceeding 96%. HA-NLC-plant extracts exhibit an appropriate level of biocompatibility at concentrations < 50 µg/mL. ArnicaM wins the antioxidant contest while RuscusA proved excellent for accelerating the wound closure process. NLCs and HA-NLCs entrapping ArnicaM manifested the highest capacity to neutralise DPPH free radicals, reaching 79.4% inhibition. BJ fibroblast cells treated with HA-NLCs closed the wound more rapidly than NLCs, with cells reaching maximum wound closure efficiency when treated with 12.5 and 100 µg/mL HA-NLC-RuscusA, followed by HA-NLC-ArnicaM-RuscusA. These results facilitate the design of remarkable hybrid lipid nanocarriers, which exploit the emergence of a pharmacological phytochemical’s synergy, and which could contribute to stimulating signalling pathways and promoting appropriate cellular regeneration, needed for wound healing. Full article

Background/Objectives: The oral administration of donepezil has been shown to have common side effects due to systemic drug delivery, with fluctuations in blood and brain donepezil concentrations. Therefore, we obtained nanostructured lipid carriers loaded with donepezil (donepezil–NLC) for nose-to-brain targeting. Methods: The obtained NLCs were characterized by measurements of particle size, the polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy, Differential Scanning Calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and in vitro release studies. Plasma and brain pharmacokinetic studies in Wistar rats were carried out to determine brain targeting. Results: Donepezil–NLC showed low polydispersity and nanometric size, high zeta potential, and high drug entrapment efficiency. Microscopy images showed spherical particles with regular surfaces. Thermal analysis, X-ray diffraction, and FTIR-ATR suggested the formation of an amorphous lipid matrix and the incorporation of donepezil molecularly dispersed within the lipid matrix. In vitro drug release studies demonstrated a biphasic drug release pattern with an initial burst followed by sustained release, with results better fitted to the Korsmeyer–Peppas model (n-value > 0.5). Following the nasal administration of donepezil–NLC, brain pharmacokinetic studies in Wistar rats demonstrated a significant improvement in bioavailability. Compared to the intravenous injection of donepezil, the AUC^0–ꝏ value was 10.5-fold higher. Drug targeting efficiency and direct transport percentage showed extremely higher values, suggesting nose-to-brain targeting after donepezil–NLC intranasal administration. Conclusions: Donepezil–NLC has proven to be an efficient drug delivery system for the nose to the brain, which may reduce systemic toxicity and improve Alzheimer’s therapy with low doses of donepezil and fewer adverse effects. Full article

The gut microbiota takes charge in a pivotal role in metabolic equilibrium, immune response, and modulating gut lining stability and has become the main focus of nutrition and functional food research. In this regard, the definition of prebiotics has progressed past the traditional approach limited to indigestible dietary fibers, embracing more targeted, biologically active, and functional delivery systems. In recent years, plant-derived exosomes (PDEs), a subclass of exosomes defined as extracellular vesicles (EVs) in the 30–150 nm size range, have emerged as an innovative class of nanostructures supporting this transformation. Plant-derived exosome-like nanoparticles (PELNs) have been taken into account as natural nanocarriers which are suitable for the gastrointestinal system with the help of their high biocompatibility, low immunogenicity profiles and rich bioactive cargo contents. This review discusses structural features of PELNs, molecular cargo content, and biological roles comprehensively and focuses especially on gut microbiota interactions. MicroRNAs, proteins, lipids, polyphenols, and glycans which PELNs contain are discussed with regard to shaping the microbial composition, regulating microbial metabolic activity, and modulating host-microbe communication. Findings derived from in vitro, in vivo, and limited translational studies indicate that PELNs can modulate specific microbial taxa, increase short-chain fatty acid (SCFA) yield, strengthen mucosal immune homeostasis, and induce source-dependent responses in the gut microbiota. In their traditional definition, prebiotics are taken into account as food components which selectively support proliferation and metabolism of helpful microbes, especially Bifidobacteria and Lactobacilli. Within this framework, PELNs are not only passive carriers of functional components but also evaluated as active systems which can directly affect microbiota composition and metabolic functions. Thus, they are repositioned as “prebiotic nanocarriers.” Also this review evaluates the potential of functional food and integration of major edible PELNs into synbiotic formulations by discussing their isolation and characterization methods and stabilities in the gastrointestinal environment. Limitations of clinical applications and lack of research from a prebiotic nanocarrier perspective of PELNs show that this field still contains important research gaps. The novelty of the study lies in its integration of PELN research with nutrition-based approaches to microbiota modulation and innovative functional food strategies under a single multidisciplinary conceptual framework. Full article

Fusarium oxysporum f. sp. lycopersici (FOL) is one of the most destructive soil-borne pathogens affecting tomato production worldwide, causing substantial yield losses and persisting in soil for extended periods. The increasing regulatory restrictions on chemical fungicides and the emergence of resistant pathogen strains have intensified the search for sustainable and environmentally friendly alternatives. This systematic review synthesizes studies published between 2000 and 2025 that evaluated the antifungal efficacy of essential oils (EOs), their bioactive constituents, and EO-based nanoformulations against FOL in tomato. A total of 40 studies were included, following the PRISMA 2020 guidelines, encompassing in vitro, greenhouse, and limited field evaluations. Many EOs rich in phenolic compounds and oxygenated monoterpenes, such as thymol, carvacrol, eugenol, citral, and menthol, consistently inhibited FOL growth and spore germination, with reported mycelial growth inhibition ranging from 60 to 100% and minimum inhibitory concentrations (MICs) between 0.05 and 1.5 µL ml⁻¹. However, the use of EOs is often limited because they evaporate quickly, do not mix well with water, can harm plants, and do not persist under field conditions. Nano-delivery systems, including nanoemulsions, polymeric nanoparticles, chitosan-based carriers, and lipid-based nanostructures, have been shown to enhance the stability, bioavailability, and antifungal efficacy of EOs. This has led to improved disease management and reduced pesticide application rates. In addition, several EO-based treatments have been reported to activate plant defense responses, including the induction of defense-related genes, antioxidant enzymes, and epigenetic modifications. Overall, EO-based nanoformulations show promise as next-generation biopesticides for the sustainable management of tomato Fusarium wilt. Nevertheless, large-scale field validation, standardized formulation protocols, and regulatory assessments are required before these technologies can be widely implemented in agriculture. Full article

Cancer poses a serious threat to human life and health, and the number of new cancer and death cases worldwide is substantial, of which breast cancer is the most common among women. p-QM-1h is an organic small molecule with excellent anti-cancer activity, but it has low solubility and requires a high dosage, and it is not a targeted anti-tumor drug. In this study, p-QM-1h was loaded into a nanostructured lipid carrier (NLC) using the thin-film dispersion method to construct p-QM-1h-NLC, and its surface was modified with cetuximab (CTX) to construct CTX-p-QM-1h-NLC, which was tested for activity in 4T1 cells and tumor-bearing mice. The construction of CTX-p-QM-1h-NLC used Miglyol 812N as a liquid lipid, which effectively improved the solubility and encapsulation efficiency of p-QM-1h. Nanoparticles were uniform, well dispersed, and had good stability, and the CTX modification of p-QM-1h-NLC exhibited high connection efficiency and ensured antibody integrity. CTX-p-QM-1h-NLC exhibited effective anti-tumor activity in both 4T1 cells and tumor-bearing mice. The construction of CTX-p-QM-1h-NLC effectively improved the solubility of p-QM-1h, enhanced its therapeutic efficacy and reduced its drug dosage. It also had a certain targeting ability, increasing drug aggregation in tumor tissues. Flow cytometry and Western blot results showed that CTX-p-QM-1h-NLC could effectively inhibit the expression of TrxR and increase the expression of Bax and caspase 3 in vivo, which was consistent with the increase in ROS levels and the induction of apoptosis in 4T1 cells. These results indicated that the construction of CTX-p-QM-1h-NLC is worthy of further investigation. Full article

Background/Objectives: Dravet Syndrome (DS) is a severe form of epilepsy that typically manifests in the first year of life and often requires polytherapy with two or more antiseizure medications (ASMs) to achieve adequate seizure control. Whereas the combination of stiripentol (STP) and cannabidiol (CBD) has demonstrated clinical efficacy, it presents significant formulation challenges due to the low aqueous solubility and poor oral bioavailability of both compounds. Furthermore, the high daily dosages of STP (approximately 50 mg/kg/day or higher) and the oily nature of conventional CBD formulations often hinder patient compliance, as pediatric patients frequently reject these treatments due to unfavorable organoleptic properties. Methods: Nanostructured lipid carriers (NLCs) containing STP and CBD suspended in an aqueous medium were developed. The formulation was optimized using Response Surface Methodology (RSM) and subjected to comprehensive in vitro and in vivo characterization. Results: The optimized formulation exhibited a mean particle size of 175.3 nm, a polydispersity index (PDI) of 0.232, a zeta potential of −8.35 mV, and an encapsulation efficiency greater than 99% for both drugs. Physicochemical characterization via atomic force microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy revealed spherical nanoparticles without aggregation, with the drugs molecularly dispersed within the lipid matrix. Both STP and CBD showed sustained release profiles and demonstrated oral pharmacokinetic profiles that were comparable or superior to current commercial products. Conclusions: This novel formulation represents a promising therapeutic alternative for DS, enabling the co-administration of STP and CBD while potentially enhancing CBD bioavailability and treatment adherence in pediatric populations. Full article

Background: The increasing prevalence of multidrug-resistant bacterial infections highlights the need for drug-delivery strategies that improve antimicrobial exposure and sustain therapeutic activity. In this study, ciprofloxacin-loaded nanostructured lipid carriers (NLC-CIP) were developed and evaluated to better understand how formulation-dependent release behavior influences antibacterial performance against Escherichia coli. Methods: NLC-CIP were prepared and characterized in terms of size, polydispersity, encapsulation efficiency, and colloidal stability. In vitro release profiles were evaluated across different pH conditions, followed by kinetic modeling. Stability under refrigerated storage was assessed. Antibacterial performance was determined through IC₅₀ measurements and dynamic growth-kinetic analyses, while cytotoxicity was evaluated in HepG2 cells. Results: Ciprofloxacin incorporation increased hydrodynamic diameter (~116 to 194 nm) while preserving low polydispersity (PdI~0.04), high colloidal stability, and encapsulation efficiency (96%). Release studies showed medium-dependent behavior, with rapid release at pH 1.2, 4.5, and 7.4, and more sustained profile at pH 6.8, consistent with diffusion-controlled kinetics (Weibull model). Refrigerated storage preserved release profiles while slowing early-stage kinetics. NLC-CIP showed improved apparent antibacterial activity, reducing the IC₅₀ from 4.9 to 1.2 ng/mL, and sustained bacterial suppression by decreasing growth rates and prolonging doubling times. Unloaded NLCs showed no antibacterial activity, and cytotoxicity assays confirmed favorable biocompatibility. Conclusions: Overall, these results show that NLC-based encapsulation can modulate ciprofloxacin release and reshape drug exposure over time, thereby improving antibacterial performance under the tested conditions. This study supports integrated release and growth-kinetic analyses as a more informative framework for evaluating lipid-based antibiotic delivery systems. Full article

Background/Objectives: A robust and scalable manufacturing framework for lipid-based nanocarriers remains a critical challenge, particularly for labile phytochemicals such as curcuminoids in turmeric. This study presents an integrated Quality by Design (QbD)-driven and Outcome-Based Design (ObD) strategy to establish a scalable, resource-efficient manufacturing process for curcuminoids-loaded nanostructured lipid carriers (NLCs). Methods: To overcome the limitations of conventional multivariate design of experiments (DOE), which require extensive experimental runs, a risk-based, knowledge-driven single-factor screening approach was employed. Guided by risk assessment tools, including Ishikawa diagrams and failure mode considerations, 12 representative processing conditions were selected to define the design space. Critical quality attributes (CQAs), namely, particle size, polydispersity index (PDI), and zeta potential, were predefined to establish a robust control strategy. A two-step homogenization process—high-shear homogenization (HSH) for pre-emulsification followed by high-pressure homogenization (HPH) for nanoscale refinement—was systematically optimized. Results: Multivariate data analysis using principal component analysis (PCA) and hierarchical cluster analysis (HCA) identified key critical process parameters (CPPs), particularly HSH speed, processing time, and HPH cycles, as dominant factors influencing nanoparticle characteristics. The optimized 1-h process enabled successful scale-up of NLCs from 100 g to 5000 g, demonstrating the capability to generate nanosized particles within 100–500 nm. The combined HSH–HPH approach produced smaller, more uniform nanoparticles with high encapsulation efficiency and physical stability, outperforming HSH alone. Conclusions: Overall, this study establishes a practical and industrially viable framework that integrates QbD principles with data-driven optimization tools, for enabling reliable translation from laboratories to semi-industrial production. Full article

Background/Objectives: Beeswax, a complex natural secretion primarily derived from Apis mellifera and Apis cerana, has evolved from an ancient remedy into a multifunctional excipient and bioactive material in modern pharmaceutical sciences. This review evaluates its physicochemical properties, pharmaceutical applications, and emerging biomedical potential, while addressing current quality and regulatory challenges. Methods: A narrative review was conducted by analyzing literature on the chemical composition, functional properties, conventional uses, advanced drug delivery applications, pharmacological activities, and quality control of beeswax, emphasizing structural characteristics, formulation roles, and integration into innovative delivery technologies. Results: Beeswax is a lipid-based matrix composed of over 300 constituents, including wax esters, hydrocarbons, and free fatty acids, conferring thermoplasticity, biocompatibility, and structural stability. Traditionally, it functions as a stiffening agent, viscosity modifier, and emulsion stabilizer in topical formulations, forming an occlusive barrier that enhances skin hydration. In advanced systems, it serves as a solid lipid matrix in nanostructured lipid carriers (NLCs), microspheres, and 3D-printed tablets, enabling controlled drug release and improved bioavailability of lipophilic compounds. It also exhibits antimicrobial, anti-inflammatory, and wound-healing activities, while beeswax-derived policosanols show potential cardiovascular and gastroprotective benefits. However, concerns regarding paraffin adulteration and pesticide contamination highlight the need for stringent analytical and regulatory oversight. Conclusions: With rigorous quality control and sustainable sourcing, beeswax remains a versatile, eco-friendly material bridging traditional medicine and advanced pharmaceutical innovation. Full article

Multidrug resistance (MDR) and chemotherapy-associated toxicity remain major challenges limiting the success of cancer treatments. In this context, berberine (BBR), an isoquinoline derivative belonging to the barberry family, has emerged as a promising adjuvant that can enhance the efficacy of chemotherapy while potentially mitigating its side effects. The findings indicate that berberine enhances the therapeutic effect of several drugs, such as doxorubicin, cisplatin, tamoxifen, and 5-fluorouracil, through multiple mechanisms including the inhibition of ABC transporters, regulation of autophagy, and synergistic enhancement of reactive oxygen species generation. Advanced pharmaceutical and nanotechnological formulations, including cyclodextrin complexes, solid dispersions, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, chitosan-based systems, and inorganic nanoplatforms, have demonstrated significant improvements in the solubility, stability, cellular uptake, and oral bioavailability of berberine. However, knowledge gaps remain regarding optimal dosage determination, safety assessment in combination therapy, and establishing efficacy in large-scale clinical trials. Incorporating berberine into combination therapy strategies may improve treatment outcomes, overcome drug resistance, and potentially reduce the toxic burden associated with chemotherapy. Therefore, this review provides a comprehensive analytical framework for berberine’s potential as an adjuvant, elucidates its mechanistic synergistic interactions with standard therapies, explores pharmaceutical strategies to overcome bioavailability limitations, and suggests future research avenues to further its clinical development. Full article

Background/Objectives: Oral diseases remain among the most prevalent noncommunicable conditions worldwide, with biofilm-driven dysbiosis playing a central role in dental caries, gingivitis, periodontitis, and oral candidiasis. Curcumin has attracted considerable interest because of its anti-inflammatory, antioxidant, antimicrobial, and regenerative properties. However, its clinical use remains limited by poor water solubility, chemical instability, rapid metabolism, and low bioavailability. This review aimed to provide a comprehensive analysis of curcumin-based nanoformulations for oral health applications, with emphasis on their mechanistic actions, antibiofilm activity, and translational relevance. Methods: This review examined representative nanocarrier systems developed for curcumin delivery in oral health. These included polymeric nanoparticles, nanomicelles and nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers, nanogels, hydrogels, mucoadhesive films, and metallic or hybrid nanosystems. The analysis focused on molecular mechanisms of action, antimicrobial and antibiofilm effects against major oral pathogens, and key translational challenges. Results/Findings: Across the reviewed studies, nanoformulations consistently improved curcumin solubility, stability, tissue penetration, mucosal retention, and controlled release. Mechanistically, they enhanced anti-inflammatory activity through inhibition of nuclear factor kappa B (NF-κB), strengthened antioxidant defenses via the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis, supported tissue repair and osteogenic responses, disrupted oral biofilms, and modulated local immune responses. Antimicrobial activity was reported against Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans, with reduced exopolysaccharide production, impaired adhesion, and improved biofilm penetration. Conclusions: Curcumin-based nanoformulations represent promising adjunctive platforms for oral healthcare. However, their clinical translation still requires improved stability in the oral-environment standardized manufacturing and characterization, rigorous safety evaluation, and well-designed controlled clinical studies. Full article

This review surveys how nanoparticles and biomolecular nanosized structures interact with model membrane systems, and how these interfacial processes govern their performance in drug and gene delivery, antimicrobial strategies, biosensing, and nanotoxicology. The nanostructures covered include polymeric nanoparticles, lipid-based carriers, peptide nanostructures, dendrimers, and multifunctional hybrids. Model membranes span Langmuir monolayers, supported lipid bilayers, vesicles/liposomes across sizes, and emerging hybrid or asymmetric constructs that better approximate native complexity. Mechanistically, interactions follow recurrent routes—surface adsorption, bilayer insertion, pore formation, and lipid extraction/reorganization—regulated by particle size, morphology, charge, ligand architecture, and lipophilicity, in conjunction with membrane composition, phase state, curvature, and asymmetry. A multiscale toolkit links structure, mechanics, and dynamics: Langmuir troughs and Brewster Angle Microscopy map thermodynamics and mesoscale morphology; atomic force microscopy and quartz crystal microbalance with dissipation resolve nanoscale topography and viscoelasticity; fluorescence microscopy/spectroscopy reports on localization and packing; neutron and X-ray reflectometry quantify vertical structure; molecular dynamics provides atomistic pathways and design hypotheses. Historically, the field advanced from early monolayers and bilayers, through the fluid mosaic model, to raft microdomains and modern biomimetic systems, enabling increasingly realistic experiments. Key advances include cross-method integration linking experimental observations with image-based computational models; persistent debates concern the translation from simplified models to living membranes, the role of dynamic coronas, and scale/force-field limits in simulations. Future efforts should prioritize hybrid models incorporating proteins and asymmetric lipidomes, standardized reporting and reference systems, rigorous coupling of experiments with calibrated simulations and machine learning, and alignment with safety-by-design and regulatory expectations, thereby shifting interfacial measurements from descriptive observation to predictive design rules. Full article

Background/Objective: Buccal delivery offers a potential route to circumvent gastrointestinal degradation and hepatic first-pass metabolism, but hydrophilic peptides typically exhibit limited mucosal permeation. Nanostructured lipid carriers (NLCs) have been proposed as delivery platforms capable of modulating interfacial interactions and improving mucosal transport. This study aimed to quantitatively evaluate the ex vivo buccal permeation of angiotensin II (Ang II), used as a hydrophilic peptide model, when associated with NLCs compared with free peptide under matched Franz diffusion cell conditions. Methods: Ang II-associated NLCs were prepared by melt emulsification combined with a low-energy injection technique. Particle size, polydispersity index, and zeta potential were determined by dynamic light scattering and laser Doppler electrophoresis. Association efficiency and drug loading were quantified by indirect spectrofluorometric analysis. Ex vivo permeation studies were conducted using porcine buccal mucosa mounted in Franz diffusion cells, and cumulative permeation, steady-state flux, and apparent permeability coefficients were calculated. Results: The NLCs exhibited nanometric size, moderate polydispersity, and association efficiency above 80%, and remained colloidally stable at 4 °C for 28 days. In ex vivo experiments, Ang II-associated NLCs showed measurable cumulative permeation, reaching approximately 9% after 2 h, whereas free Ang II was not detected in the receptor compartment under the tested conditions. Conclusions: This work provides a quantitative ex vivo buccal transport comparison of a hydrophilic peptide model delivered as NLC-associated versus free peptide under matched Franz cell conditions. The findings support further investigation of NLC-based approaches for buccal delivery of vasoactive peptides and provide a rational basis for future in vivo evaluation of mucosal delivery performance and systemic exposure. Full article