Search Results (468)

Background/Objectives:Artemisia annua essential oil (EO) possesses diverse biological activities; however, its practical application is limited by volatility, instability, and poor bioavailability. This study aimed to develop chitosan-coated nanostructured lipid carriers (CH-NLCs) for efficient encapsulation and delivery of A. annua EO and to evaluate their physicochemical characteristics and biological performance. Methods: The nanoformulation exhibited favorable physicochemical properties, including a high encapsulation efficiency (85.97 ± 1.30%) and a strongly positive surface charge (approximately +45 mV), indicating good colloidal stability. Structural analyses by SEM, FTIR, and XRD confirmed successful encapsulation of the EO within the nanocarrier matrix. Results: The CH-NLC formulation significantly enhanced larvicidal activity against Aedes aegypti larvae, reducing the LC₅₀ value from 213 ppm for the free EO to 142 ppm. Enhanced antifungal activity was also observed, with 47–56% greater inhibition against Malassezia furfur, Trichophyton mentagrophytes, and Candida albicans compared with the free EO. Furthermore, CH-NLC demonstrated improved cytotoxic activity against skin cancer cell lines, achieving IC₅₀ values of 21.4 ± 1.7 µg/mL and 30.1 ± 1.6 µg/mL against A431 and A375 cells, respectively, while maintaining lower toxicity toward normal HaCaT keratinocytes. Mechanistic investigations revealed enhanced apoptosis and an approximately 3-fold increase in intracellular reactive oxygen species (ROS) levels in treated cancer cells. Conclusions: Collectively, these findings indicate that chitosan-coated nanostructured lipid carriers effectively improve the stability and biological efficacy of A. annua essential oil and represent a promising platform for future biomedical and biocidal applications. Full article

The growing demand for effective delivery of active ingredients in cosmetic formulations has stimulated the development of advanced carrier systems. This study evaluates the potential of the dicephalic di-N-oxide surfactant N,N-bis [3,3-(dimethylamino)-propyl]dodecylamide (C₁₂-(DAPANO)₂) as a stabilizer for aqueous dispersions of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Lipid nanoparticles were prepared using three classes of solid lipids—cetyl palmitate, glyceryl behenate, and stearic acid—through high-speed homogenization followed by ultrasonication. Their physicochemical properties were characterized using DLS, TEM, AFM, DSC, and TGA. All formulations exhibited particle sizes below 300 nm and a low polydispersity index (<0.30), indicating good uniformity. High absolute zeta potential values and stability studies confirmed excellent physical stability, with all dispersions remaining stable for at least 90 days at room temperature. Compared with bulk lipids, nanoparticles showed lower melting temperatures and reduced crystallinity. NLCs exhibited lower crystallization and melting temperatures than SLNs and displayed a more spherical morphology. Cytotoxicity assessment using J774.E macrophages revealed no adverse effects. These findings highlight the surfactant’s potential as a stabilizing agent for lipid-based cosmetic nanocarriers, supporting the development of stable systems with improved active ingredient loading and controlled release properties. Full article

Background/Objective: Topical therapy remains a cornerstone in managing fungal infections due to the deep-seated nature of the pathogens and the persistence of the disease. Ketoconazole (KTZ) is a broad-spectrum antifungal agent, but its highly lipophilic nature presents considerable challenges in developing effective topical formulations. Additionally, oral KTZ has been subject to labeling restrictions and market withdrawal due to its association with severe hepatic adverse effects. This study was conducted to design, optimize, and evaluate KTZ-loaded nanolipid carriers (NLCs; KTZ-NLCs) as a delivery platform that could improve cutaneous bioavailability and enhance antifungal activity. Methods: The optimized KTZ-NLCs were further incorporated into a mucoadhesive system (KTZ-NLCs-C) through the inclusion of Carbopol^® 940 NF, aiming to improve the retention of the formulation on the skin surface. NLCs were characterized in terms of their physical appearance, particle size, polydispersity index, zeta potential, pH, viscosity, drug content, and entrapment efficiency. The optimized KTZ-NLC and KTZ-NLCs-C formulations were subsequently assessed for in vitro drug release, ex vivo skin permeation and deposition, as well as in vivo skin irritation. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KTZ over 24 h. The ex vivo transdermal flux and permeability coefficient of KTZ from the lead KTZ-NLCs-C formulation were approximately 2.8-fold greater than those achieved with the marketed cream formulation. The in vivo skin irritation studies indicate that NLC-based formulations are suitable for topical applications. The lead formulation was stable for 90 days (the final time point evaluated) under refrigerated and room-temperature storage conditions. Conclusions: These findings suggest that the NLC-based system is a promising platform for the topical delivery of KTZ and has the potential to enhance the therapeutic outcomes for patients with superficial fungal infections. Full article

Effective hand washing takes time and hand sanitizers that contain alcohol have a number of drawbacks, and frequent use of alcohol may cause skin damage. The objective of this study is to formulate nanostructured lipid carrier systems containing chlorhexidine digluconate to be applied topically for hand hygiene, especially for people sensitive to alcohol. A cytotoxicity experiment was conducted to ascertain the safe dosage for each of the three nano-cream formulas (F1, F2 and F3). Following each treatment, the viral titer was assessed using tissue culture infectious dose₅₀ and standard plaque assays. The selected formulation was characterized rheologically. Furthermore, fifteen volunteers of various ages and genders participated in the vivo antimicrobial test of the selected formulation as a hand sanitizer. All of the formulas were found to be safe. Using the disc diffusion method, the three formulations exhibited in vitro antimicrobial effects against different microbes. F1 showed biphasic release, reasonable skin deposition and spherical droplets under a microscope. F1 exhibited a non-Newtonian shear thinning flow behavior. After 30 min, the reduction values for rotavirus and Phix-174 were 21 and 4%, respectively. Additionally, the impact of F1 was assessed on the infectivity of simian rotavirus sa-11 (ds RNA) and Phix-174 (ss DNA) bacteriophage. According to the findings of the in vivo study, the percentage of total bacterial counts that were removed varied from 91 to 100%. Moreover, the range of the removal percentage of total fungi was 95.38 to 100%. In summary, F1 can be used as an economic, safe, and effective hand antiseptic. It can also completely replace alcohol in the market. Full article

Background/Objectives: Lipid-based nanocarriers have emerged as promising systems for improving the delivery of poorly soluble drugs by enhancing stability, bioavailability, and controlled release. This work aimed to formulate solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing ciprofloxacin (CIP) using solvent-free procedures. Methods: The systems were extensively characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and atomic force microscopy (AFM) to study the nanoparticles in the solid state. Furthermore, in vitro drug release was evaluated, and mathematical modeling was applied to analyze the resulting release kinetics. Additionally, storage stability was assessed at 4 °C and 25 °C over a period of 8 months. Results: The results indicated that SLN with an average size of ~50 nm (SLN 50) and NLC with mean diameters of ~25, 50, and 100 nm (NLC 25, NLC 50 and NLC 100 respectively) were successfully prepared. DLS measurements showed narrow particle size distributions (PdI ≤ 0.2) and negative zeta potentials ranging from −3.7 to −7.7 mV. Encapsulation efficiencies were remarkably high for most systems, reaching ~98% for SLN 50, NLC 50, and NLC 100, while the smallest formulation (NLC 25) showed a lower efficiency (~80%). Both TEM and AFM confirmed the formation of spherical nanoscale structures consistent with the sizes determined by DLS. Release studies revealed a strong influence of particle size on kinetics: NLC 25 exhibited rapid release (~95% within 30 min), whereas NLC 100 showed a sustained profile (<20% after 6 h). Dissolution profiles were accurately described by the Lumped-Gonzo kinetic model (R² > 0.98), enabling estimation of dissolution efficiency. Conclusions: These findings confirm that lipid-based nanocarriers can be engineered to precisely control CIP release. Full article

Background: Schistosomiasis remains a major neglected tropical disease, with praziquantel (PZQ) as the only widely used treatment, despite its limitations. Parthenolide (PTL), a sesquiterpene lactone, exhibits potent in vitro antischistosomal activity; however, its poor aqueous solubility, low oral bioavailability, and chemical instability may limit its in vivo efficacy. Objective: This study investigated whether nanoencapsulation in nanostructured lipid carriers (NLC) could enable the in vivo antischistosomal activity of PTL. Methods: PTL was isolated from Tanacetum parthenium and incorporated into NLC using hot emulsification followed by ultrasonication. The resulting formulation (NLC-PTL) was physicochemically characterized, and its in vivo antischistosomal efficacy was evaluated in a murine model of Schistosoma mansoni infection. Results: NLC-PTL exhibited nanoscale size, low polydispersity, high encapsulation efficiency, and sustained drug release. In vivo, free PTL showed no significant effect on worm burden, whereas NLC-PTL achieved a marked reduction (77.9%) in adult worms and significantly decreased egg output compared to controls (p < 0.001). Blank NLC had no antiparasitic effect. Conclusions: Nanoencapsulation was associated with in vivo antischistosomal activity of PTL compared to the free compound. These findings suggest that formulation strategies may influence the in vivo performance of lipophilic natural products in schistosomiasis. Full article

Aquaculture faces increasing challenges from bacterial diseases and the widespread use of antibiotics, which contribute to antimicrobial resistance and environmental concerns. Oregano oil–lauric acid cationic nanostructured lipid carriers (OE-L⁺NLCs) were developed in this study and their antibacterial activity and safety were evaluated in Nile tilapia (Oreochromis niloticus). The nanoparticles were prepared using a hot homogenization–ultrasonication method and characterized based on their particle size, surface charge, morphology, and release profile. Antibacterial activity was assessed against six isolates of Streptococcus agalactiae using minimum inhibitory and bactericidal concentration assays, while their stability was evaluated under different storage conditions and simulated gastrointestinal environments. In vivo safety was determined through median lethal concentration analysis, survival assessment, and histopathology. The developed OE-L⁺NLCs showed a mean particle size of 175.90 ± 4.94 nm, positive zeta potential of +44.02 ± 0.54 mV, and low polydispersity index (0.15 ± 0.00). The formulation exhibited sustained carvacrol release (70.46 ± 0.96% over 24 h) and strong antibacterial activity against all six isolates, with MIC and MBC values of 0.25 and 0.25–0.49 mg/mL, respectively. The nanoformulation maintained antibacterial activity during 90 days of storage and under simulated gastric conditions. In vivo toxicity assessment showed that OE-L⁺NLCs exhibited a higher LC₅₀ value (11.11 mg/mL) than free oregano oil (5.89 mg/mL), together with improved survival and reduced histopathological alterations in Nile tilapia. Overall, the formulation provides an effective and stable delivery platform for natural antimicrobials, offering a promising alternative to antibiotics for sustainable disease management in aquaculture. Full article

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