Search Results (457)

Background: Oral delivery of chemotherapeutic agents remains challenging due to gastrointestinal degradation, poor intestinal permeability, and extensive first-pass metabolism, which collectively limit bioavailability. Lipid-based drug delivery systems offer a promising strategy to overcome these barriers. This study aimed to develop a freeze-dried, solid-dispersible self-emulsifying drug delivery system (SEDDS) using a water-in-oil-in-water (w/o/w) double emulsion approach for the co-encapsulation of hydrophilic (doxorubicin) and lipophilic (ellipticine) agents to enhance oral delivery. Methods: Double-emulsion SEDDS were prepared via a two-stage emulsification process to enable compartmentalized drug loading within aqueous and oil phases. The formulations were freeze-dried to improve stability and storage. Physicochemical properties were characterized using dynamic light scattering for droplet size and polydispersity index (PDI), zeta potential analysis for colloidal stability, and differential scanning calorimetry for thermal behavior. Drug encapsulation efficiency was determined, and cellular uptake was evaluated in breast cancer cells using fluorescence microscopy. Results: Optimized SEDDS exhibited droplet sizes of 90–347 nm with low PDI values (0.005–0.336), indicating uniform and stable dispersions. Zeta potential values (−10.64 to 2.38 mV) supported colloidal stability, while freeze-dried formulations retained dispersion characteristics upon reconstitution over extended storage. Both drugs demonstrated high encapsulation efficiency (>97%), and thermal analysis confirmed the formation of stable amorphous systems. Fluorescence imaging revealed enhanced intracellular uptake of both agents. Conclusions: This study demonstrates that freeze-dried double-emulsion SEDDS enable efficient co-delivery of hydrophilic and lipophilic drugs, improving stability and cellular uptake. This platform shows strong potential for overcoming key barriers in oral chemotherapy and provides a promising strategy for combination drug delivery. Full article

Background/Objective: The introduction of Ketoconazole (KZ, Nizoral^®) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient topical formulations. Moreover, oral KZ has undergone labeling revisions and market withdrawal due to serious hepatic side effects. This study aimed to design, optimize, and evaluate KZ-loaded nanoemulsions (NEs; KZ-NEs) as a delivery platform that could improve skin bioavailability and antifungal activity. Methods: Optimized KZ-NEs were converted to a mucoadhesive formulation (KZ-NEC) by the addition of Carbopol^® 940 NF to enhance the adherence of the formulations to the skin surface. NEs were evaluated concerning physical appearance, globule size, polydispersity index, zeta potential, pH, viscosity, and drug content. Optimized KZ-NE and lead KZ-NEC formulations were further evaluated for in vitro release, ex vivo skin permeation and deposition, skin irritation, and in vivo studies. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KZ over 24 h. The ex vivo permeability coefficients of KZ from the optimized KZ-NE and lead KZ-NEC formulations were approximately four- and three-fold greater than that achieved with the marketed cream formulation, respectively. In addition, the C_max of the lead KZ-NEC formulation (14.4 ± 1.1 μg/mL) was significantly higher (p < 0.05) compared with the marketed cream formulation (10.5 ± 0.5 μg/mL). Moreover, in vitro antifungal susceptibility testing showed that KZ demonstrated improved antifungal efficacy when incorporated into the KZ-NE and KZ-NEC formulations. Neither of the NE-based formulations caused any alterations in skin color or morphology during the 24 h visual observation period. Both NE-based formulations were stable for 90 days (the last time-point tested) at three different storage conditions. Conclusions: NE-based formulation could serve as an effective topical delivery platform for KZ and could improve therapeutic outcomes for patients with topical fungal infections. Full article

Marine macroalgae are a rich source of bioactive natural products, although the application of many lipophilic compounds is limited by poor aqueous solubility and instability. This study investigated metabolites isolated from the South African brown seaweed Sargassum incisifolium and evaluated a solid lipid nanoparticle (SLN) system to improve their physicochemical properties and enable bioactivity studies. Five metabolites, including one previously unreported derivative and four known metabolites (including fucoxanthin), were isolated and characterized using standard chromatographic and spectroscopic techniques. SLNs composed of stearic acid and Poloxamer 188 were prepared via hot homogenization and characterized using dynamic light scattering, scanning electron microscopy, thermogravimetric analysis, and NMR, which confirmed the efficient encapsulation of the lipophilic compounds. Antimicrobial activity against clinically relevant bacterial and fungal pathogens was evaluated using a resazurin-based microdilution assay, with results expressed as percentage growth relative to untreated controls. The pure compounds exhibited moderate, concentration-dependent activity, while the SLN formulations improved dispersibility, and in several cases, reduced % growth or produced more consistent responses, particularly against Gram-positive bacteria and Candida auris. Although activity remained lower than that of conventional antimicrobials, these findings demonstrate that SLN-based delivery enables functional evaluation of hydrophobic marine metabolites and supports further development of Sargassum-derived natural products. Full article

Background/Objectives: β-Caryophyllene is a plant-derived sesquiterpene with recognized therapeutic potential; however, high lipophilicity and low aqueous solubility limit its parenteral application. Nanoemulsion-based systems represent a rational strategy to address these challenges. This study aimed to develop and physicochemically characterize an injectable β-caryophyllene nanoemulsion and to evaluate its preclinical safety following intramuscular administration. Methods: Five nanoemulsions (NBCP1–NBCP5) were prepared by low-energy emulsification using different hydrophilic–lipophilic balance (HLB) values and characterized in terms of particle size, polydispersity index, zeta potential, and encapsulation efficiency. The optimized formulation (NBCP1) was evaluated in a 14-day subacute intramuscular toxicity study in male Wistar rats (n = 5 per group) at doses of 5 and 15 mg/kg. Clinical observations, food and water intake, body weight, hematological and biochemical parameters, and histopathological analyses of muscle, liver, and kidney tissues were assessed. Results: NBCP1 exhibited favorable physicochemical properties, including a mean particle size of 102.39 nm, PDI of 0.27, zeta potential of −27.5 mV, and encapsulation efficiency of 97.16%, and remained stable under stress conditions. Repeated intramuscular administration did not induce behavioral alterations, changes in consumption patterns, or differences in body weight between the control and treated groups. Hematological and biochemical parameters remained within physiological ranges, and histopathological analysis revealed preserved tissue architecture without inflammatory or degenerative changes. Conclusions: The results support the suitability of NBCP1 as a stable nanoemulsion platform for the parenteral delivery of β-caryophyllene under the evaluated conditions. These findings address the limited information available on injectable formulations of this sesquiterpene and provide a foundation for future pharmacokinetic, longer-term safety, and efficacy studies. Full article

Reversible emulsion drilling fluids integrate the advantages of water-based and oil-based systems, offering solutions to critical challenges in shale oil and gas development. However, conventional reversible emulsions face limitations including poor stability, high cost, and material scarcity. This research introduces widely available, eco-friendly modified nanocrystalline cellulose (MNCC) as a sustainable alternative. While current reversible drilling fluids primarily depend on organoclays and adopt aqueous phases containing 20–25% CaCl₂ for shale inhibition, pH-responsive MNCC was validated as an effective reversible emulsifier capable of stabilizing emulsions through 48 consecutive phase-inversion cycles. Enhanced emulsion stability was achieved with organoclay at an optimal dosage (≤2.5 g/100 mL), and a composite interfacial film superior to the film formed by pure MNCC was fabricated via the combination of organoclay and MNCC. Increasing the organoclay content elevated the acid requirements for phase inversion (due to its lipophilicity) but reduced the alkali needs. Finally, higher CaCl₂ concentrations in the aqueous phase reduced the acid demand for inversion yet increased alkali consumption and diminished stability in both oil-in-water (O/W) and water-in-oil (W/O) emulsions. These effects are attributed to the dual role of CaCl₂ in compressing the electrical double layer and modifying phase density differences, synergistically governing reversible inversion behavior. This research provides a foundation for applying nanocrystalline cellulose-stabilized reversible emulsion drilling fluids, offering practical solutions for efficient development of sensitive reservoirs like shale. Full article

Fisetin (FIS) is a bioactive flavonoid with antioxidant, anti-inflammatory, and anticancer activity, but its poor aqueous solubility and high lipophilicity limit its therapeutic use. In this study, three-component FIS-loaded mixed micelles based on Poloxamer 407 (P407) or Poloxamer 188 (P188), sodium deoxycholate, and Kolliphor HS15 or Kolliphor ELP were developed and comparatively evaluated. The formulations were prepared by the thin-film hydration method and characterized in terms of physicochemical properties, storage stability, solid-state properties, and in vitro biological activity. All freshly prepared formulations formed nanosized systems with high encapsulation efficiency. Although P188-based micelles showed smaller initial particle sizes, P407-based systems exhibited superior stability after lyophilization and rehydration. Formulations containing Kolliphor ELP showed the most favorable stability profile over 28 days of storage. FT-IR, TG, DSC, and XRPD analyses confirmed successful incorporation of FIS into the polymeric matrix and transformation of the drug into an amorphous or molecularly dispersed state. In vitro studies demonstrated that micellar encapsulation enhanced the cytotoxic activity of FIS against MICH-2 melanoma cells compared with the free compound, while P407-based systems showed a more favorable safety profile toward MRC-5 fibroblasts. These findings indicate that P407-based mixed micelles, particularly those containing Kolliphor ELP, may serve as promising nanocarriers for improving FIS delivery with potential relevance for dermal and anticancer applications. Full article

Salvia transsylvanica was investigated as a source of bioactive metabolites by optimizing hydroethanolic ultrasound-assisted extraction (UAE) and comparing it with classical preparations. A D-optimal quadratic design was applied to aerial parts to evaluate the effects of ultrasonic amplitude, extraction time, and ethanol concentration on total phenolic content (TPC) and antioxidant capacity (ABTS, DPPH), yielding models with good fit and predictive ability. The optimal conditions (24% amplitude, 12 min, 38% ethanol) were then applied to aerial parts, flowers, and leaves, affording extracts with high TPC values (up to 240 mg GAE/g extract) and antioxidant activities comparable to aqueous infusions and 70% hydroethanolic macerates, with FRAP and DPPH values above 400 mg TE/g dw. Targeted HPLC-MS analysis revealed a Salvia-typical phenolic profile dominated by rosmarinic acid (up to 20 mg/g extract), methyl rosmarinate, caffeic acid derivatives, salvianolic acid K, and flavone glycosides (luteolin-7-O-glucoside and apigenin-7-O-glucoside), with leaf extracts generally richest in phenolics and antioxidant capacity. Conversely, macerates showed superior recovery of phytosterols and tocopherols. The extracts displayed moderate, selective antibacterial effects, particularly against Staphylococcus aureus, with inhibition zones up to 4 mm for flower-based preparations. Overall, UAE emerged as an efficient, green strategy for a rapid recovery of phenolic antioxidants from S. transsylvanica, while classical maceration complements it for lipophilic constituents, supporting the valorization of this endemic sage. Full article

Background/Objectives: Hyperthermia coupled with temperature-triggered drug delivery systems, including drug-loaded thermosensitive liposomes, that exhibit increased membrane permeability at hyperthermia-relevant temperatures is a promising therapeutic strategy for cancer treatment. Our previous study revealed that nitrogen-doped carbon dots (CD) partially interact with the phospholipids of liposomes, increasing the membrane permeability of an encapsulated anticancer drug. In vitro cell experiments indicated that their presence in the culture medium, albeit at relatively high concentrations, also affect cell membrane permeability, enhancing drug internalization in cancer cells. This study aims to introduce either hydrophilic or lipophilic carbon dots into liposomes and evaluate them as thermosensitive drug delivery systems. Methods: Alkylated carbon dots (CD-C16) were synthesized and liposomal systems with either the lipophilic CD-C16 or the parent hydrophilic CD were prepared and efficiently loaded with doxorubicin (DOX). Following physicochemical characterization, their thermosensitivity was studied vs. time and temperature, while their effect on cell survival at 37 and 40 °C was evaluated against HEK293 and PC3 cells. Results: At 40 °C, for CD containing liposomes 50% DOX release is observed, whereas for CD-C16 containing liposomes 95% DOX is released within 5 min. Against PC3 cells at 40 °C, both DOX-loaded CD containing liposomes and CD-C16 containing liposomes are more potent compared to the parent drug-loaded liposomes, whereas CD-C16 containing liposomes are equally potent to free DOX. Against HEK293 cells the thermosensitive formulations at 40 °C prove even more cytotoxic, with CD-C16 containing liposomes being more potent than free DOX, but CD containing liposomes are advantageous for being less toxic than free DOX at 37 °C. Conclusions: Although work is needed to elucidate the mechanism at the molecular level, the results suggest that it is possible to adjust liposomal membrane permeability through the incorporation of carbon dots in order to optimize performance for hyperthermia-based applications. Full article

The ongoing substance use crisis in the United States involves a broad range of illicit and prescription drugs, including opioids, stimulants, sedatives, and various psychoactive and non-psychoactive compounds. Traditional surveillance methods rely on self-reported data, which could lead to bias and recall inconsistencies. Wastewater-based epidemiology has emerged as a powerful, non-invasive tool for monitoring community-level drug use, offering near real-time estimates and the potential to serve as an early warning system. However, challenges such as analyte degradation, wastewater variability, and matrix effects can affect data quality and comparability across regions. This study presents a standardized, practical workflow for multi-drug (n = 52) detection in wastewater, aiming to minimize analyte loss and improve reproducibility. Composite samples were collected from multiple U.S. cities, transported on ice, and extracted using solid-phase extraction. Extraction efficiencies were compared using Oasis Hydrophilic-Lipophilic-Balanced and Mixed-mode Cation-Exchange (MCX) cartridges, with the MCX sorbent providing complementary reversed-phase and cation-exchange interactions that enabled the retention of chemically diverse compounds across multiple drug classes. Analysis was performed with an Ultra-High-Performance Liquid Chromatography system coupled to a triple quadrupole mass spectrometer, in which the instrument parameters and critical methodological considerations, including sample handling, transport, column selection, and method validation, are detailed. This work contributes to the development of a robust, scalable protocol for multi-drug surveillance in wastewater, supporting timely, data-driven public health responses and informing national drug policy efforts. Full article

Astaxanthin (AST), despite its high bioactivity, exhibits poor stability and low bioavailability due to its strong lipophilicity and inherent degradation susceptibility. To overcome such a challenge, we developed a food-grade oleogel delivery system using a soy protein–arabinoxylan (SA) glycosylated complex modulated by different concentrations (0.5–3%) of sucrose ester (SE) or soy lecithin. We show that the emulsifier concentration has a non-linear effect on the oleogel microstructure: an optimal level of 1% had a significant impact on the interfacial compactness and network density, giving rise to improved thermal stability, rheological strength and AST encapsulation efficiency (81.27%). During in vitro digestion, the SA matrix in combination with emulsifiers allowed gastric protection and intestinal-targeted release of AST with a bioaccessibility of up to 88.84% (SAO-SE-AST). This controlled release profile directly translated into enhanced in vivo antioxidant efficacy in wild-type Bristol N2 Caenorhabditis elegans, as evidenced by reduced lipofuscin accumulation, elevated thermotolerance (survival rate: 64.44–73.33%), suppressed reactive oxygen species levels and activation of endogenous antioxidant enzymes (superoxide dismutase as well as glutathione peroxidase). Collectively, this research has uncovered that food-grade emulsifiers are not only stabilizers, but also key regulators of oleogel architecture and bioactive functionality. These results provide a structure–digestion–bioactivity correlation for protein–polysaccharide oleogels, representing a rational design strategy for high-performance delivery systems of lipid-soluble nutraceuticals. Full article

Epidermal Growth Factor (EGF) plays an important role in skin regeneration and repair by promoting cell proliferation and collagen synthesis. However, its topical application is limited by low stability, susceptibility to degradation, and poor penetration through the stratum corneum due to its hydrophilic nature and relatively large molecular size. Microencapsulation offers a strategy to protect sensitive bioactives and improve their delivery in cosmetic formulations. In this study, EGF was encapsulated in Arabic gum/gelatine A (AG/GE) coacervate microcapsules and incorporated into a hydrating cream. The work extends previous studies using the same microcapsule composition for lipophilic compounds, demonstrating its applicability for a hydrophilic bioactive and highlighting the versatility of the encapsulation platform. The resulting microcapsules exhibited spherical, multinucleated morphology with an encapsulation efficiency of 78.8 + 1.0%. Although diffusion of microencapsulated EGF in the cream could not be directly determined, the formulation showed trends towards improvement in several skin parameters during the volunteer evaluation, including reduction in surface spots (31%), brown spots (21%) and pore visibility (10%), and improved texture (22%). A 25% decrease in transepidermal water loss and a 33% increase in elasticity suggested improved skin barrier function. Volunteers reported high acceptance regarding non-irritancy, texture, and sensory experience. Full article

Background/Objectives: Compounded vaginal creams are widely used for conditions such as hormone replacement therapy, vaginal dryness, low libido, vaginal infections, etc. Recent research highlights the potential of using anhydrous bases to extend shelf life, particularly when combined with self-emulsifying and mucoadhesive properties that improve mucosal retention and enhance drug bioavailability. This study provides in vitro and ex vivo evaluation of an anhydrous vaginal base. Methods: Key quality indicators such as irritation potential, leakage potential, pH compatibility, mucoadhesion, and self-emulsification were assessed using the chorioallantoic membrane Hen’s Egg Test, MTT assay, texture analysis, and fluorescence microscopy. Results: The anhydrous vaginal base demonstrated high cell viability (>78%) and non-irritant potential (IS = 2.5) in in vitro assays. It maintained physiological vaginal pH (4.56 ± 0.05), showed strong mucoadhesive properties comparable to commercial products, and exhibited minimal leakage. Ex vivo studies confirmed its prolonged retention on vaginal tissues. The anhydrous vaginal base formed stable emulsions upon contact with vaginal fluid simulant, effectively distributing both lipophilic and hydrophilic compounds. Conclusions: Compared to water-containing bases, an anhydrous vaginal base shows advantages: longer retention time and lower leakage; adaptability to varying vaginal fluid levels; and efficient dispersion of both hydrophilic and lipophilic active pharmaceutical ingredients. These features support its potential use in compounded vaginal products, minimizing stability risks and enhancing patient compliance and therapeutic outcomes. Full article

Kaurenoic acid (KA) is an ent-kaurane diterpenoid present in several medicinal plant species and has been reported to exhibit anti-inflammatory, cytotoxic, and analgesic activity in experimental models. Despite its pharmacological profile, the development of KA as a therapeutic agent has been hindered by its unfavorable physicochemical and biopharmaceutical properties. KA is highly lipophilic and poorly soluble in water, which limits its dissolution, systemic exposure, and oral bioavailability. These limitations are common among plant-derived bioactive compounds and pose significant challenges for clinical development. Lipid-based nanocarrier systems, particularly liposomal formulations, have therefore been investigated as potential delivery strategies for improving the biopharmaceutical performance of KA. Encapsulating KA within phospholipid bilayers can improve its apparent solubility, protect it from degradation, and modify its biodistribution compared to the free compound. In this review, we discuss the pharmacological mechanisms of KA, its physicochemical properties, and the biopharmaceutical barriers to its therapeutic development. We also critically evaluate published studies on nanocarrier-based formulations, focusing on encapsulation efficiency, particle size, release properties, and pharmacokinetics (PK). Additionally, regulatory and pharmaceutical considerations relevant to lipid-based delivery of KA are addressed. Available evidence supports lipid-based nanocarriers as a promising strategy to improve preclinical development and formulation performance of poorly soluble plant bioactives such as kaurenoic acid. Although KA-loaded nanocarriers demonstrate encouraging activity in preclinical models, comprehensive pharmacokinetic and safety evaluations remain necessary before clinical development can be realistically considered. Full article

This study explores the sustainable extraction, quantification, and functional evaluation of antioxidant amphiphilic (TAC) and lipophilic (TLC) compounds from avocado (Persea americana) products and by-products using green, solvent-efficient extraction, for potential applications in functional foods and/or cosmetics. Juice derived from organically grown domestic (Greek) avocado and the remaining juicing pulp by-products were subjected to a green extraction and partitioning fractionation process to obtain separately the extracted TLC and TAC. Quantitative analyses of total phenolic (TPC) and carotenoid contents (TCC), as well as antioxidant activity (DPPH, ABTS, FRAP), were performed using UV–Vis spectroscopy just after the extraction. ATR–FTIR spectroscopy was used to structurally characterize TAC bioactives compared to standards (gallic acid, quercetin, beta-carotene, soy phospholipids). TAC extracts exhibited higher TPC and superior antioxidant capacity across all assays, in comparison to the TLC, especially in the by-products. Despite relatively modest absolute phenolic and carotenoid concentrations compared to the literature, the extracts retained potent bioactivity, indicating selective enrichment of functional compounds. UV–Vis spectral peaks (240 nm, 310 nm) confirmed the presence of conjugated systems, suggesting potential for anti-UV photo-protective cosmetic applications. ATR–FTIR analysis further identified functional groups of key amphiphilic constituents, including simple phenolics, flavonoids, polyphenols, carotenoids and polar lipids. TAC extracts were successfully integrated into plant-based jelly prototypes as functional food supplements. Antioxidant stability of the jelly was retained for 15 days under refrigeration, though shelf-life limitations due to moisture and microbial growth highlight the need for preservative strategies. This work demonstrates a circular bioeconomy approach to food waste valorization, with significant implications for sustainable innovation in functional foods and clean-label cosmetics. Full article

Micronutrient deficiencies, particularly of vitamins A, D₃, and folic acid, remain a significant global health challenge despite established dietary recommendations. This study proposes a novel fortification strategy using advanced emulsion technology to enrich extra-virgin olive oil (EVOO) with these essential micronutrients. Water-in-oil (W/O) and double oil-in-water-in-oil (O/W/O) emulsions were designed to enable the simultaneous encapsulation of lipophilic (A and D₃) and hydrophilic (folic acid) vitamins within a single functional food matrix. Vitamin concentrations were quantified using high-performance liquid chromatography (HPLC) coupled with a photodiode detector (PDA) to evaluate retention during processing. Bioaccessibility was assessed by subjecting vitamin-enriched emulsions to a standardized in vitro digestion model simulating gastrointestinal conditions. Results showed significantly higher incorporation efficiency in the O/W/O system compared to conventional W/O emulsions, regardless of the physicochemical properties of the vitamins. Both lipophilic (A and D₃) and hydrophilic (folic acid) compounds exhibited a satisfactory retention, highlighting the versatility of the double-emulsion approach. This study represents the first report of simple and multiple oil-continuous emulsions that simultaneously incorporate vitamins A, D₃, and folic acid, providing preliminary evidence of their stability and gastrointestinal release under simulated digestion conditions. Full article