Search Results (1,060)

Background/Objectives: α-lipoic acid (ALA) shows therapeutic potential but faces poor aqueous solubility (BCS Class II), gastric instability, and low oral bioavailability (~30%). This work investigated the formulation of cyclodextrin (CD) inclusion complexes of ALA to overcome the aforementioned limitations and improve nutraceutical applications. Methods: Phase solubility studies in simulated gastric and intestinal fluids screened for optimal CD, followed by molecular dynamics simulations and MM-PBSA binding free energy calculations. Inclusion complexes of choice were prepared by grinding, spray-drying, and lyophilization, followed by solid-state characterization (DSC/XRPD/FTIR). Further analysis was performed using pH-shift dissolution (USP II), permeability (PermeaPad^®, Caco-2), and (photo)stability according to ICH. Results: Hydroxypropyl-β-cyclodextrin (HPβCD) emerged as the optimal host due to favorable complexation, as confirmed by phase solubility studies and supported by molecular modeling, which revealed a favorable balance between inclusion complex stability and pH-triggered drug release. Formulations based on spray-dried and lyophilized HPβCD–ALA complexes (HPβALA-sd and HPβALA-lyo), in which ALA was fully amorphized, achieved near-complete dissolution within five minutes under biorelevant pH-shift conditions. This performance markedly exceeded that of free ALA (approximately 66% dissolution at pH 7.4) while maintaining moderate permeability (Papp 8–9 × 10⁻⁶ cm/s). Storage stability was enhanced markedly (88–90% ALA retention after 6 months at 40 °C/75% RH vs. 36% for free ALA) while UV stability was not improved through CD-complexation, probably due to interaction of UV-VIS light with the exposed portion of ALA. Conclusions: Even though the permeability of ALA–CD inclusion complexes remained medium (Papp ~ 8–9 × 10⁻⁶ cm/s) and unaffected by complexation, a significantly improved dissolution profile indicates better expected bioavailability compared to pure ALA. 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

Transferosomes are liposome-derived ultradeformable vesicles designed to improve drug delivery across restrictive biological barriers, particularly in non-invasive administration routes. Their structure is based on phospholipid bilayers modified with edge activators, usually surfactants or bile salts, which increase membrane flexibility while preserving vesicular organization. This balance between deformability and stability distinguishes transferosomes from conventional liposomes and has supported their use in dermal, transdermal, ocular, nasal, buccal, and other mucosal delivery systems. However, despite extensive experimental interest, the field remains limited by inconsistent terminology, heterogeneous formulation strategies, non-harmonized deformability assays, and incomplete translation from laboratory formulations to clinically relevant products. This review critically examines transferosomes from a formulation-development perspective, focusing on the relationship between lipid composition, edge-activator selection, vesicle properties, deformability, drug release, and biological performance. Particular attention is given to critical quality attributes, analytical characterization, mechanistic interpretations of barrier interaction, and the unresolved debate between intact vesicle penetration, drug-release-dominated delivery, and barrier perturbation. Transferosomes are also positioned in comparison with conventional liposomes, ethosomes, and transethosomes. Finally, the review identifies key unmet needs related to standardization, reproducibility, scalability, storage stability, and regulatory uncertainty. By integrating formulation design with mechanistic and translational analysis, this review aims to clarify when transferosomes offer a genuine delivery advantage and which parameters must be controlled to support their further pharmaceutical development. Full article

Background: 5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone (DHPV) is a postbiotic gut microbiota-derived flavanol metabolite with reported anti-inflammatory activity. Despite growing interest in its potential dermatological applications, its pharmaceutical properties and suitability for topical delivery have not been systematically investigated. This study aimed to perform the first comprehensive preformulation and formulation-oriented evaluation of DHPV and to develop stable topical ointment formulations suitable for further dermatological research. Methods: The physicochemical properties of DHPV were characterized using powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), quantitative solubility assessment, and excipient compatibility studies. Based on the obtained preformulation data, two anhydrous ointment formulations containing DHPV were developed. The formulations were evaluated for homogeneity, rheological behavior, chemical stability under accelerated storage conditions, and in vitro drug release performance. Results: DHPV was identified as a crystalline compound with heterogeneous particle morphology and limited aqueous solubility. Quantitative solubility studies demonstrated the highest solubility in PEG 300 and glycol-based solvents. Compatibility testing revealed increased impurity formation in hydrophilic environments, whereas lipophilic excipients provided improved chemical stability. Both ointment formulations exhibited acceptable physical characteristics and maintained DHPV stability throughout accelerated storage. However, marked differences in release behavior were observed. The lipid–wax formulation showed significantly higher release rates, lower variability, and more reproducible release profiles than the petrolatum-based reference formulation, indicating more efficient diffusion of DHPV from the semisolid matrix. Conclusions: The physicochemical characteristics of DHPV strongly influence formulation design and performance. Anhydrous lipid-based systems provide a favorable environment for maintaining DHPV stability, while formulation composition significantly affects drug release. The developed lipid–wax formulation represents a promising platform for future skin permeation, pharmacodynamic, and efficacy studies. Full article

Background: Acute drug poisoning is one of the leading causes of admission to pediatric emergency departments and represents a significant public health concern because of its potential severity and associated morbidity and mortality. This study aimed to describe the clinical, epidemiological, and severity characteristics of pediatric patients with acute drug poisoning treated at a tertiary care hospital in western Mexico. Methods: A retrospective, observational, descriptive study was conducted in the pediatric emergency department of Nuevo Hospital Civil de Guadalajara “Dr. Juan I. Menchaca” from January 2016 to December 2024. Results: The mean age of the patients was 77.1 months, with a predominance of females (61.9%). Most poisoning events (97.1%) occurred in the home. Accidental poisoning was the most frequent mechanism (54.5%), followed by suicide attempts (24.4%) and drug overdoses (17.6%). Regarding medical care, 50% of patients arrived at the emergency department within the first four hours after exposure, and 55.1% had a hospital stay of less than 12 h. The most involved drug groups were anxiolytics, mainly benzodiazepines (21.6%), followed by polypharmacy (17.6%) and antiemetic use (13.6%). The most frequent toxidrome was hypnotic–sedative syndrome (42.6% of cases). Multivariate analysis showed that exposure to anticonvulsants was significantly associated with a longer hospital stay (odds ratio [OR] = 7.31, p = 0.003). Most cases were classified as mild according to the Poisoning Severity Score, and no deaths were reported. Conclusions: Although pediatric drug poisoning generally has a favorable prognosis, it remains a significant public health issue. These findings highlight the need for targeted preventive strategies, including caregiver education, safe medication storage at home, and increased awareness and training programs for both families and healthcare professionals. Full article

Feline Infectious Peritonitis (FIP) has been transformed from a fatal disease to a treatable condition following the introduction of GS-441524, a nucleoside analogue targeting feline coronavirus replication. However, the widespread use of unregulated compounded formulations and the absence of validated analytical tools for therapeutic drug monitoring (TDM) represent critical gaps in clinical FIP management. This study describes the development and full ICH M10-compliant validation of a high-throughput LC-MS/MS method for the quantification of GS-441524 in feline serum, incorporating an automated protein precipitation protocol and a PBS-BSA surrogate matrix in accordance with 3Rs principles. The method met all acceptance criteria across validated parameters, including linearity (0.1–50 µg/mL), accuracy (bias within ±12.5%), precision (CV ≤ 10.9%), selectivity, extraction recovery (87.5–107.9%), and stability under clinically relevant storage conditions. Matrix equivalence between PBS-BSA and authentic feline serum was confirmed, enabling routine calibration without animal-derived materials. The validated method was applied to clinical TDM in cats undergoing GS-441524 treatment for FIP, providing preliminary evidence of inter-individual pharmacokinetic variability. The compounded formulations administered to the TDM cohort were independently verified by LC-MS/MS, confirming drug content within ±15% of labelled claims and excluding pharmaceutical quality as a confounding factor in the interpretation of serum drug concentrations. Full article

Background/Objectives: Ursodeoxycholic acid (UDCA) is a bile acid widely used for the treatment of cholestatic liver diseases; however, its poor aqueous solubility represents a major limitation for the development of oral liquid formulations, particularly in pediatric patients requiring accurate and flexible dosing. This study aimed to develop and characterize a fully solubilized extemporaneous UDCA oral formulation using the ready-to-use vehicle Wagner, with particular emphasis on the role of hydroxypropyl-β-cyclodextrin (HP-β-CD) as a solubilizing excipient. Methods: Phase-solubility studies, Job’s plot analysis, and ¹H NMR spectroscopy were performed to investigate the host–guest interaction between UDCA and HP-β-CD, confirming the formation of a stable 1:1 inclusion complex responsible for a marked increase in drug solubility. The aqueous solubility of UDCA increased from approximately 0.02 mg/mL in water to 31 ± 1 mg/mL in the Wagner base containing HP-β-CD, compared to ~10 mg/mL in the corresponding cyclodextrin-free vehicle. Chemical stability was evaluated using an HPLC method adapted from the European Pharmacopoeia, employing dual detection (refractive index and photodiode array detector) to ensure specificity and stability-indicating capability. Results: The UDCA solution (20 mg/mL) remained chemically stable for at least 4 months under refrigerated (4–8 °C) and room temperature (25 °C) conditions, with only moderate degradation observed at 40 °C. Physical stability studies confirmed the absence of precipitation, phase separation, or significant pH variations under all storage conditions. Conclusions: Wagner-based formulation enabled the development of a stable and homogeneous UDCA oral solution, providing a complementary formulation strategy to conventional suspension-based preparations. This approach represents a robust and patient-oriented strategy for extemporaneous compounding, particularly suitable for pediatric use. 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

Three-dimensional (3D) cardiac models, including spheroids, organoids, and organ-on-chips, are advanced systems for studying human physiology, disease, and drug responses with greater biological relevance than 2D models. As their use expands in biomedical research, tissue engineering, and regenerative medicine, reliable preservation methods are needed. However, cryopreservation often fails to protect 3D systems due to limited cryoprotectant penetration, ice formation, and mechanical stress during freezing and thawing. Room-temperature (RT) preservation has emerged as a promising alternative for short-term transport. This study evaluated a RT-based transport medium (CellShip^®) for preserving cardiac organoids for up to seven days, compared with conventional cryopreservation using slow-freezing in Cryostor^®CS10. Viability and functionality were assessed using apoptosis, ATP levels, beating activity, proliferation, and size. During maturation, organoids showed increased size, ATP levels, and beating capacity. Cryopreservation reduced size, proliferation, ATP levels, and altered beating, while increasing apoptosis. In contrast, RT preservation maintained stable viability and functionality after recovery. These findings demonstrate that RT preservation effectively maintains cardiac organoid integrity and function, offering a promising alternative for short-term storage and transport, with potential terrestrial and nonterrestrial applications. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) remains difficult to treat because systemic therapy is constrained by limited selectivity, resistance, and toxicity. This study aimed to engineer selenium–chitosan nanoparticles loaded with sunitinib (SeNPs-Ch-SUN) to enhance hepatic delivery and improve anticancer activity against HCC. Methods: The developed system was characterized for particle size (PS), zeta potential (ZP), loading efficiency (LE%), in vitro release, and storage stability. Their cytotoxicity was evaluated in parental HepG2 and Huh-7 cells, multidrug-resistant HepG2 cells, SUN-resistant Huh-7 cells, and THLE-2 normal hepatocytes. In vivo hepatic distribution after intravenous administration was also assessed in rats. Results: SeNPs-Ch-SUN exhibited a mean PS of 93.62 ± 1.06 nm, positive ZP of +24.47 ± 1.31 mV, and LE of 83.8 ± 2.16%. FTIR supported drug association with the chitosan-stabilized selenium system. Compared with free sunitinib, SeNPs-Ch-SUN exhibited sustained drug release, with 51.17 ± 1.26% released at 24 h, whereas the free drug was almost completely released within 3 h. This controlled-release behavior translated in vivo into prolonged hepatic retention and superior liver exposure after intravenous administration. SeNPs-Ch-SUN significantly increased liver AUC_0–24 to 77.23 ± 10.56 µg/g·h, compared with 36.39 ± 9.66 µg/g·h for free SUN, corresponding to an approximately 2.1-fold increase in hepatic exposure. SeNPs-Ch-SUN enhanced cytotoxicity in parental and resistant HCC models, lowered IC₅₀ values, improved selectivity toward malignant cells, and reduced resistance index (RI) in MDR-HepG2 cells, while maintaining reduced toxicity toward normal hepatocytes relative to the free SUN. Conclusions: SeNPs-Ch-SUN represents a promising liver-directed nanoplatform for sunitinib delivery. Full article

Edible insects have emerged as a promising alternative to conventional livestock as the global demand for sustainable protein sources rises. Ensuring the safety of insect-based foods is crucial for consumer acceptance and regulatory approval. This review provides a comprehensive overview of the primary chemical and microbiological contaminants associated with edible insects, including heavy metals, pesticides, veterinary drugs, persistent organic pollutants (POPs), mycotoxins, microbiological hazards, and allergenic risks. Current evidence indicates that, when insects are farmed and processed under controlled conditions and in compliance with existing European Union regulations, contaminant levels are generally low and within the range of those found in traditional animal-derived foods. Most studies report that current risks are primarily linked to substrate quality and storage practices. Allergenic risks, particularly cross-reactivity with crustacean and mite allergens, remain a crucial consideration for individuals with sensitivities. Despite these reassuring findings, knowledge gaps persist regarding insect-specific contaminant limits, the metabolic fate of toxins, and the long-term safety of consuming novel insect-derived products. Continued research, targeted monitoring, and regulatory adaptation will be essential to ensure the safe and sustainable integration of insect-based foods into the human diet. Full article

Background/Objectives: Obesity is a complex disease involving the accumulation of an excessive amount of body fat. It is a condition that develops when energy intake and expenditure are out of balance. Inflammation and hypertrophy are caused by the storage of too much white adipose tissue, resulting in adiposity, which also secretes several pro-inflammatory cytokines. Several marketed drugs used to treat obesity have many side effects from long-term ingestion. Other therapeutic compounds from marine sources have already been established for treating obesity. In this paper, the main aim is to establish the anti-obesity effect of derived omega-3 fatty acids, i.e., 20:3(n-3)11-14-17 Icosa Trienoic Acid from Setipinna phasa oil. Methods: In the present investigation, inbred male Swiss albino mice were segregated into six categories as Control, Positive Control, Obese Control, and 20:3(n-3)11-14-17 Icosa Trienoic Acid treated groups with three different doses: Treatment 1, Treatment 2 and Treatment 3. To establish the potentiality of extracted fatty acid, different parameters would be considered, such as body weight, lipid composition and different obesity and obesity-associated inflammation markers. Results: After the isolated compound from Setipinna phasa oil was applied to the treated mice group, it decreased their body weight and serum lipid profile by 39.05%, 62.69%, 62.72%, and 78.46% compared to obese mice. They also had lower levels of uric acid, Serum Glutamic-Oxaloacetic Transaminase, Serum Glutamic Pyruvic Transaminase, and Alkaline Phosphatase, at 67.52%, 57.09%, 64.80%, and 43.99%, than the obese group. Accordingly, the treated group’s expression of genes linked to obesity and pro-inflammatory cytokines was downregulated. The isolated compound affected both anti-inflammatory and anti-obesity markers’ increased expression. Conclusions: After the experiments, it was found that the possibility of using fatty acids might be helpful as an anti-inflammatory and anti-obesity therapeutic strategy. This therapeutic strategy will be cheap and cost-effective. Full article

Rapeseed meal (RSM) represents one of the most abundant yet underutilized alternative plant protein sources, offering a compelling nutritional profile and diverse bioactive compounds with direct relevance to human nutrition and health. Its major storage proteins, including 12S globulin cruciferin and 2S albumin napin, along with phenolic compounds, have been associated with antioxidant, antihypertensive, and potential antimicrobial activities. Beyond these health-promoting properties, RSM-derived storage proteins are emerging building blocks for nanocarriers, with potential applications in drug delivery systems. Recent studies have advanced extraction, purification, and modification strategies for RSM bioactive compounds. However, relatively little attention has been given to how specific molecular interactions between phenolics and proteins modulate functional properties and bioactivity. This review, therefore, provides an updated analysis of the bioactive profile of RSM bioactive compounds, the associated phenolic–protein interactions, and their functional potential. Additionally, we also discuss the current challenges and future opportunities for integrating RSM bioactive compounds into biotechnology and multi-product biorefinery schemes. Full article

Background: Hot-melt extrusion (HME) is a promising technology for the manufacturing of drug products; however, its application is limited by elevated thermal and shear stresses that may induce degradation of thermolabile active pharmaceutical ingredients. One of the approaches to reducing processing temperatures is the use of polymeric systems with tailored thermal and rheological properties. The aim of the study was to develop an approach for the design of polymeric systems exhibiting a transient plasticization window, enabling a reduction in melt viscosity and improved processability under low-temperature extrusion conditions, followed by the formation of a structurally coherent matrix upon cooling. Methods: The compatibility of the initial polymers was assessed using laser microinterferometry. Based on the obtained data, three- and four-component polymeric compositions were designed and prepared by hot-melt extrusion. The resulting materials were characterized by differential scanning calorimetry, melt rheology analysis, and storage stability assessment. Thermal and rheological data were used to iteratively optimize the polymeric systems. Results: A four-component polymeric system based on PVP K-29/32, PEG 400, PEG 1500, and HPC EF was developed, suitable for processing by hot-melt extrusion at 70 °C. The final system enabled formation of a homogeneous extrudate, exhibited reproducible rheological behavior, and remained stable in the solid-state during storage, with no evidence of cold flow. Conclusions: It was established that, in the design of polymeric systems for hot-melt extrusion, the key factor is not achieving the lowest possible glass transition temperature, but rather the design of a system in which viscosity is transiently reduced under processing conditions and followed by structural stabilization upon cooling. The proposed approach may be applied in the development of polymeric premixes for the preparation of dosage forms by hot-melt extrusion, including those incorporating thermolabile active pharmaceutical ingredients. Full article

Background/Objectives: Residues of β-lactam antibiotics in foods of animal origin are important for official residue control and public-health risk assessment. Sample storage conditions may affect the measured concentrations of these analytes, whereas cooking may influence consumer exposure. This study evaluated the stability of six β-lactam antibiotics—amoxicillin, ampicillin, phenoxymethylpenicillin, benzylpenicillin, cefazolin, and cefotaxime—and clavulanic acid, a β-lactamase inhibitor, in chicken meat during storage and thermal processing. Methods: Incurred chicken meat samples were obtained after in vivo administration of the studied compounds. Stability was assessed during storage at +4 °C, −20 °C, and −86 °C for up to 165 days, during repeated freeze–thaw handling, and during heating at 100 °C for up to 30 min. The target compounds were quantified by HPLC–MS/MS after acetonitrile extraction and hexane clean-up. Results: The studied compounds were unstable at +4 °C, with concentrations decreasing below the detection limit within 3–27 days depending on the compound. Storage at −20 °C was insufficient for long-term preservation of most penicillins, whereas −86 °C improved stability. Cefazolin was the most stable compound under the tested storage conditions, while cefotaxime was the least stable. Heating at 100 °C for 30 min caused substantial reduction in parent-compound concentrations, ranging from 63.8 ± 4.0% for cefazolin to complete disappearance below the detection limit for cefotaxime. Conclusions: For reliable official residue analysis, chicken meat samples intended for β-lactam testing should be stored at −86 °C whenever long-term storage is required. Repeated thawing should be avoided. Cooking substantially reduces the concentrations of the parent compounds but cannot be considered a reliable safety measure, because degradation may be incomplete and degradation products were not assessed in this study. Full article