Search Results (124)

Background: Epigallocatechin-3-gallate (EGCG), a potent green tea polyphenol, possesses significant therapeutic potential, but its clinical application is limited by poor gastrointestinal stability and low oral bioavailability. To address this, a novel herbal nanomedicine-based delivery system was developed utilizing D-α-tocopheryl polyethylene glycol succinate (TPGS) and Poloxamer 407. Objectives: This study aims to develop and characterize EGCG-loaded TPGS/Poloxamer 407 micelles, evaluating their physicochemical properties, storage stability, in vitro drug release profile, in vivo oral bioavailability, and preliminary tolerability observation. Methods: The micelles were prepared using the film hydration method followed by lyophilization. Results: The optimized 2:2 TPGS-to-poloxamer 407 weight ratio yielded EGCG-loaded micelles, displaying a mean particle size of 15.4 nm, a polydispersity index (PDI) of 0.16, a zeta potential of −17.7 mV, an encapsulation efficiency of 82.7%, and a drug loading capacity of 7.6%. The critical micelle concentration (CMC) was determined to be 0.00125% w/v. Transmission electron microscopy (TEM) confirmed the micelles’ uniform spherical morphology. In vitro release studies demonstrated a sustained release profile in both simulated gastric and intestinal fluids. EGCG formulation remained stable for at least six months when stored at 4 °C. No adverse clinical signs were noted during the 28-day tolerability observation. In vivo pharmacokinetic evaluation in mice revealed a significant elevation in oral bioavailability, achieving a 2.27-fold increase in area under the curve (AUC) and a 1.8-fold increase in peak plasma concentration (Cmax) compared to free EGCG. Conclusions: Collectively, these findings underscore the potential of the TPGS/poloxamer 407-based micelle system as a promising oral delivery platform for EGCG, enhancing its stability and pharmacokinetic performance. Full article

Lutein is one of carotenoids in the human brain that is consistently associated with all cognitive performance indicators, and its levels are closely linked to age-related cognitive decline. However, lutein application is limited by its poor stability and low bioaccessibility. In this study, a lutein-loaded delivery system was developed to enhance stability and achieve brain-targeting effects. Using high-speed shear and ethanol hydration methods, PEGylated lutein liposomes with lactoferrin (Lf-LLips) were constructed and characterized. The morphology was observed using TEM and AFM. Particle sizes and lutein retention rates were evaluated under different temperatures (4 °C, 25 ± 2 °C, 50 °C), light (diffusion light, DL; light shielding, LS), and storage durations at 28 d. Compared with free lutein, the in vitro release behavior and permeability across the blood–brain barrier of the systems were investigated. Lf-LLips exhibited a particle size of 186.63 ± 2.04 nm and a potential of −30.53 ± 1.65 mV, and the lutein encapsulation efficiency was 83.11 ± 1.67%. When stored under LS, the particle size of Lf-LLips remained under 190 nm at 4 °C for 28 days, and the retention rate of lutein exceeded 80%. The release curve of Lf-LLips in vitro over 72 h followed the Weibull model. Furthermore, the permeability across the blood–brain barrier model within 12 h was 22.73 ± 1.42%. These results demonstrate that Lf-LLips significantly improve the stability of lutein and exhibit sustained-release properties along with brain-targeting efficiency. The findings demonstrate the promising future of lutein for applications in brain health enhancement. Full article

Hydroethanolic Cucurbita pepo seed extracts are traditionally used for alleviating lower urinary tract symptoms (LUTS), yet their mechanisms remain unclear. Adenosine, a purine nucleoside involved in neuromodulation and smooth muscle relaxation, was recently identified in C. pepo seeds. Since A₁ adenosine receptors (A₁AR) suppress parasympathetic bladder overactivity by inhibiting acetylcholine (ACh) release, we investigated to which extent purines from pumpkin seed extracts contribute to A₁AR activation. Complementary antioxidant capacity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Three hydrophilic seed extracts containing different adenosine levels (0.60–1.18 mg/g dw) were evaluated for agonist activity using a cAMP inhibition assay. The most active extract showed an EC₅₀ of 40.22 µg/mL. Selective removal of adenosine shifted the dose–response curve rightward, while further elimination of an adenosine derivative increased the EC₅₀ to 212.10 µg/mL, confirming adenosine as the principal active compound. Guanosine and inosine did not exhibit A₁AR agonist or allosteric effects. All samples exhibited measurable but weak antioxidant activity (IC₅₀ = 1.02–4.19 mg/mL), consistent with their low total phenolic content. These findings underscore the importance of accounting for naturally occurring agonists in plant extracts to avoid overestimating receptor-mediated effects in vitro which are not translatable in vivo. Full article

Background: Skin mycoses affect approximately 10% of the global population, and the range of effective topical antifungal agents remains limited. Voriconazole (VRC) is a broad-spectrum triazole with proven efficacy against drug-resistant fungal infections. This study aimed to develop and optimize VRC-loaded microemulsion (ME) polymer gels (Carbopol^®-based) for cutaneous delivery. Selected formulations also contained menthol (2%) as a penetration enhancer and potential synergistic antifungal agent. Methods: A comprehensive screening was performed using pseudoternary phase diagrams to identify stable oil/surfactant/co-surfactant/water systems. Selected MEs were prepared with triacetin, Etocas™ 35, and Transcutol^®, then gelled with Carbopol^®. Formulations were characterized for pH, droplet size, polydispersity index (PDI), and viscosity. In vitro VRC release was assessed using diffusion cells, while ex vivo permeation and skin deposition studies were conducted on full-thickness human skin. Rheological behavior (flow curves, yield stress) and texture (spreadability) were evaluated. Antifungal activity was tested against standard strain of Candida albicans and clinical isolates including a fluconazole-resistant strain. Results: The optimized ME (pH ≈ 5.2; droplet size ≈ 2.8 nm) was clear and stable with both VRC and menthol. Gelation produced non-Newtonian, shear-thinning hydrogels with low thixotropy, favorable for topical application. In ex vivo studies, performed with human skin, both VRC-loaded gels deposited the drug in the epidermis and dermis, with no detectable amounts in the receptor phase after 24 h, indicating retention within the skin. Menthol increased VRC deposition. Antifungal testing showed that VRC-containing gels produced large inhibition zones against C. albicans, including the resistant isolate. The VRC–menthol gel exhibited significantly greater inhibition zones than the VRC-only gel, confirming synergistic activity. Conclusions: ME-based hydrogels effectively delivered VRC into the skin. Menthol enhanced drug deposition and demonstrated synergistic antifungal activity with voriconazole. Full article

Background/Objectives: Reflecting the interaction between dissolution and absorption, the biphasic dissolution system is an appealing approach for estimating the intestinal absorption of drugs in humans. The study aims to characterize the suitability of the biphasic in vitro dissolution testing to set up an in vitro–in vivo correlation (IVIVC) for the original and generic immediate-release (IR) tablets of a Biopharmaceutics Classification System (BCS) Class II drug, bicalutamide (BIC). Methods: USP apparatus II paddle was used to conduct dissolution testing. A level A IVIVC was obtained between in vitro partitioning and in vivo absorption data of the original drug. The single-compartmental modeling was used for pharmacokinetic (PK) analysis. The generic product’s plasma concentrations were estimated. Results: There was a good correlation between in vitro and in vivo data (r² = 0.98). The area under the concentration–time curve (AUC) and maximum plasma concentration (C_max) ratios for generic/original were 1.04 ± 0.01 and 0.951 ± 0.026 (mean ± SD), respectively. Conclusions: The biphasic dissolution testing may present an in vivo predictive tool for developing generic products of poorly soluble and highly permeable drugs such as BIC, which are characterized by pH-independent poor solubility. Full article

Background: Natural products have been used worldwide as alternatives to treat or prevent different chronic diseases. Euterpe oleracea Mart. (açaí) has bioactive molecules in its chemical matrix, such as epicatechin, apigenin, and cyanidin-3-O-rutinoside. These molecules guarantee açaí’s antioxidant, anti-inflammatory, and antitumor potential. Açaí’s chemical matrix is susceptible to degradation. Nanocarriers are appropriate to use with NP. The aim of this study was to produce, characterize, and analyze the in vitro safety profile of a nanoemulsion (NE) containing açaí extract. Methods: Different NEs were prepared with açaí extract (0.83–20 mg/mL). A characterization was performed considering physical–chemical parameters and a morphological analysis. The most stable NE was evaluated for in vitro safety in fibroblasts. Fibroblasts were exposed to a concentration curve of NEs for 24 h. Cellular viability and proliferation, the levels of nitric oxide, reactive oxygen species (ROS), and the release of dsDNA were measured. Possible DNA damage was also measured. Results: It was possible to determine that the NE with 4 mg/mL of açaí extract was the most stable under refrigeration, presenting a favorable in vitro safety profile since fibroblasts kept their homeostasis aspects under most of the concentrations tested as well as their DNA integrity. Conclusion: The obtained results show that a stable NE was produced, maintaining the NP antioxidant capacity and non-toxic effects in fibroblasts. Full article

Background: Docetaxel (Doc) resistance in prostate cancer (CaP) patients is associated with the secretion of proinflammatory cytokines that induce an interaction between tumor cells and macrophages. Tumor cell-derived cytokines released in response to increased intracellular concentrations of Doc attract monocytes and macrophages to the tumor site and induce Doc resistance. Objectives: To generate Doc-resistant CaP cell line LNCaP-Doc/R and determine if we could modulate/reduce proinflammatory signals by administering Doc, encapsulated in a PLGA: Chitosan core-shell hierarchical nanoparticle (HNP-Doc) in the resistant and naive CaP Cells. Methods: LNCaP-Doc/R cells were generated by intermittent increasing concentration of Doc, proliferation, growth curve and cytotoxicity of Doc and HNP-Doc were evaluated followed by LNCaP and LNCaP-Doc/R (Doc resistant) CaP cells co-cultured with U937 monocytes with either free Doc or HNP-Doc encapsulated Doc, and various cytokine levels were measured in the conditioned media to assess the cytokine levels. Results: Our results show that LNCaP-Doc-R cells had slower growth in the lag phase, needed a 90-fold increase in Doc concentration to achieve 50% killing. Basal levels of cytokines secreted by LNCaP and LNCaP-Doc/R cells in response to free Doc and HNP-encapsulated Doc differed considerably, with free Doc-treated cells demonstrating, on average, 2–7-fold higher pro-inflammatory cytokine levels as compared to HNP-encapsulated Doc. The levels of pro-inflammatory cytokines, such as IFNγ, IL-1α, and RANTES, were increased ~2.38, ~2.75, and ~5.75-fold, respectively, in free Doc-treated CaP cells and were significantly lower when Doc was delivered via HNP. Further, LNCaP-Doc/R cells co-cultured with U937 had significantly lower markers of macrophage differentiation in response to HNP-encapsulated Doc treatment as opposed to free Doc treatment. Conclusions: Based on this analysis, we conclude that Doc treatment in vitro is associated with a proinflammatory response involving cytokines linked to macrophage recruitment and activation, with a lesser proinflammatory response with HNP-encapsulated Doc treatment. Full article

In the field of degradable metals, Zn-based implants have gradually gained more attention. However, the relatively slow degradation rate compared with the healing rate of the damaged bone tissue, along with the excessive Zn²⁺ release during the degradation process, limit the application of Zn-based implants. The use of intermetallic compounds with more negative electrode potentials as sacrificial anodes of Zn-based implants is likely to be a feasible approach to resolve this contradiction. In this work, three intermetallic compounds, MgZn₂, CaZn₁₃, and Ca₂Mg₆Zn₃, were prepared. The phase structures, microstructures, and relevant properties, such as thermal stability, in vitro degradation properties, and cytotoxicity of the compounds, were investigated. The XRD patterns indicate that the MgZn₂ and CaZn₁₃ specimens contain single-phase MgZn₂ and CaZn₁₃, respectively, while the Ca₂Mg₆Zn₃ specimen contains Mg₂Ca and Ca₂Mg₆Zn₃ phases. After purifying treatment in 0.9% NaCl solution, high purity Ca₂Mg₆Zn₃ phase was obtained. Thermal stability tests suggest that the MgZn₂ and CaZn₁₃ specimens possess good thermal stability below 773 K. However, the Ca₂Mg₆Zn₃ specimen melted at around 739.1 K. Polarization curve tests show that the corrosion potentials of MgZn₂, CaZn₁₃, and Ca₂Mg₆Zn₃ in simulated body fluid (SBF) were −1.063 V_SCE, −1.289 V_SCE, and −1.432 V_SCE, which were all more negative than that of the pure Zn specimen (−1.003 V_SCE). Clearly, these compounds can act as sacrificial anodes in Zn-based implants. The immersion tests indicate that these compounds were degraded according to the atomic ratio of the elements in each compound. Besides that, the compounds can efficiently induce Ca-P deposition in SBF. Cytotoxicity tests demonstrate that the 10% extracts prepared from these compounds exhibit good cell activity on MC3T3-E1 cells. Full article

Background/Objectives: The accurate prediction of drug release profiles from Poly (lactic-co-glycolic acid) (PLGA)-based drug delivery systems is a critical challenge in pharmaceutical research. Traditional methods, such as the Korsmeyer-Peppas and Weibull models, have been widely used to describe in vitro drug release kinetics. However, these models are limited by their reliance on fixed mathematical forms, which may not capture the complex and nonlinear nature of drug release behavior in diverse PLGA-based systems. Method: In response to these limitations, we propose a novel approach—DrugNet, a data-driven model based on a multilayer perceptron (MLP) neural network, aiming to predict the drug release data at unknown time points by fitting release curves using the key physicochemical characteristics of PLGA carriers and drug molecules, as well as in vitro drug release data. We establish a dataset through a literature review, and the model is trained and validated to determine its effectiveness in predicting different drug release curves. Results: Compared to the traditional Korsmeyer–Peppas and Weibull semi-empirical models, the MSE of DrugNet decreases by 20.994 and 1.561, respectively, and ($R^2$) increases by 0.036 and 0.005. Conclusions: These results demonstrate that DrugNet has a stronger ability to fit drug release curves and better capture nonlinear relationships in drug release data. It can deal with the nonlinear change of data better, has stronger adaptability and advantages than traditional models, and overcomes the limitations of the mathematical expressions in traditional models. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) constitutes over 84% of all lung cancer cases and is a leading cause of cancer-related mortality globally. Alectinib, a second-generation anaplastic lymphoma kinase (ALK) inhibitor, is effective in ALK-positive NSCLC; however, its clinical potential is hampered by poor aqueous solubility and limited oral bioavailability. This study aimed to develop Alectinib-loaded chitosan–alginate nanoparticles (ACANPs) to enhance its solubility, oral bioavailability, and therapeutic efficacy. Methods: ACANPs were synthesized using a novel combined solid/oil/water (s/o/w) emulsification technique with ionotropic gelation. Characterization was performed using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with ACANPs. Cytotoxicity against NSCLC cell lines (A549 and H460) was assessed using MTT assays. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: ACANPs showed a high encapsulation efficiency (~97%), an average particle size of 161 nm, and a positive zeta potential of +21 mV. In vitro release studies revealed a threefold increase in drug release from ACANPs over 48 h compared to free Alectinib. Cytotoxicity assays demonstrated significantly reduced IC₅₀ values for ACANPs. Pharmacokinetic analyses showed an enhanced maximum plasma concentration (C_max) and area under the curve (AUC), indicating a 78% increase in oral bioavailability. Conclusions: ACANPs substantially improved the solubility, cytotoxic efficacy, and oral bioavailability of Alectinib, suggesting their potential as a promising nanocarrier system for enhancing NSCLC treatment outcomes. Full article

Background: Rheumatoid arthritis is a chronic autoimmune disease that leads to severe disability and requires improved therapeutic strategies to optimize anti-inflammatory treatment. This study aimed to address this challenge by developing and characterizing an extended-release polymer matrix tablet containing ketoprofen and a ketoprofen–β-cyclodextrin complex with enhanced therapeutic properties. The objective was to improve inflammation management and therapeutic outcomes using a novel delivery system based on the inclusion of the active substance in cyclodextrin complexes. Methods: Tablets were formulated using ketoprofen and ketoprofen–β-cyclodextrin complexes combined with hydrophilic polymers such as Carbopol^® 971P NF, Kollidon^® VA 64, and Methocel^TM K4M. The complexes were obtained via the coprecipitation method to improve bioavailability. The kinetics of the release of ketoprofen, ketoprofen–β-cyclodextrin complex (2:1), and ketoprofen–β-cyclodextrin complex (1:1) from the tablets were investigated in vitro in artificial gastric and intestinal fluids, and drug release profiles were established. Advanced mathematical models were used to describe the nonlinear behavior of the drug–polymer systems. Results: The inclusion of ketoprofen in the β-cyclodextrin complexes was confirmed, revealing distinct release profiles. Tablets (K-3 F-3) containing the 1:1 complex showed rapid release (96.2% in 4–7 h), while tablets (K-1 F-4) containing free ketoprofen released 76% over 9–11 h. Higher polymer concentrations slowed the release due to gel barrier formation. Pharmacotechnical and stability tests supported their suitability as extended-release forms. A multifractal modeling approach described the release dynamics, treating the polymer–drug matrix as a complex system, with release curves characterized by variations in the fractal dimension and resolution. Conclusions: Specific hydrophilic polymer combinations effectively prolonged ketoprofen release. The developed matrix tablets, which were evaluated via in vitro studies and mathematical modeling, show promise for improving therapeutic outcomes and patient compliance during rheumatoid arthritis treatment. Full article

Objectives: This study explores the development and evaluation of a bilayer sustained-release (SR) tablet formulation of ruxolitinib. As a BCS Class 1 drug, ruxolitinib requires twice-daily dosing due to its short half-life. We designed a bilayer tablet that integrates immediate-release (IR) and SR components in varying ratios to achieve sustained plasma concentrations, which we evaluated using discriminative analysis. Methods: Bilayer tablets combining IR and SR components were prepared in different ratios. In vitro dissolution tests and pharmacokinetic studies were conducted using Beagle dogs, followed by the evaluation of in vivo–in vitro correlation (IVIVC), along with a discriminative pharmacokinetic analysis focused on the SR layer. Results: A discriminative pharmacokinetic and IVIVC analysis was applied to all bilayer tablets, offering clearer insights into the plasma concentration and dissolution profiles. Pharmacokinetic studies showed that test formulation F4, which has a 20:20 IR-to-SR ratio, is expected to provide a similar area under the curve (AUC) while prolonging exposure compared to the reference IR tablet. Conclusions: This study highlights the potential of a bilayer tablet approach, combined with discriminative pharmacokinetic and IVIVC analysis, for creating a sustained-release dosage form of ruxolitinib. Full article

Background/Objectives: Atorvastatin (ATR), an antihyperlipidemic drug with a potential antibacterial effect, was investigated in this study. Like other statins, ATR has been repurposed for several uses, ranging from anti-inflammatory to antimicrobial applications, and has demonstrated successful results. However, the efficacy of ATR is limited by its low solubility, indicating an opportunity for its encapsulation in a nanotechnology-based drug delivery system. Methods: Nanostructured lipid carrier (NLC) formulations were prepared using high-pressure homogenization and ultrasonication. The formulations were characterized, including their particle size, polydispersity index, zeta potential, encapsulation efficiency, and in vitro release. Antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) was evaluated using the growth curve (bacterial growth over time) and well diffusion methods (zone of inhibition and minimum inhibitory concentration (MIC) determination). The crystal violet assay was employed to assess biofilm inhibition. Results: The NLC formulations were optimized, and the size and zeta potential of the blank nanoparticles were 130 ± 8.39 nm and −35 ± 0.5 mV, respectively. In comparison, the encapsulated NLCs had a size of 142 ± 52.20 nm and a zeta potential of −31 ± 1.41 mV. The average encapsulation efficiency was 94%, and 70% of the drug was released after 24 h. The ATR-loaded NLCs showed significantly enhanced antibacterial activity by reducing the minimum inhibitory concentration by 2.5-fold for E. coli, 1.8-fold for S. aureus, and 1.4-fold for MRSA, and promoting more effective bacterial growth inhibition. Notably, biofilm inhibition was significantly improved with ATR-NLCs, achieving 80% inhibition for S. aureus, 40% for E. coli, and 30% for MRSA, compared to free ATR (p < 0.001). These findings suggest that NLC encapsulation enhances ATR’s antimicrobial efficacy and biofilm suppression. Conclusions: This study identified NLCs as successful carriers of ATR, significantly enhancing its antibacterial efficacy and biofilm inhibition capabilities. This formulation, which shows antimicrobial potential against both Gram-positive and Gram-negative bacteria, should be further studied and developed against different resistant microbial strains. Full article

Today, most anti-acne treatments employ topical and systemic antibiotics such as erythromycin and clindamycin, which induce cutaneous dysbiosis with adverse side effects to the skin’s normal microbiota, consequently leading to the emergence of antimicrobial resistance. In our quest to discover natural anti-acne bioactives as alternatives, we undertook a research program with the aim to identify a new blend of active ingredients based on the monoterpene phenol moiety. Within this program, we evaluated the in vitro anti-acne efficacy of thymol, Curcuma turmerones and their patented combination “Acnocure” in a cosmetic formulation. The minimum inhibitory concentration (MIC) of Acnocure against C. acnes (ATCC 6919), S. aureus (ATCC 6538), S. epidermidis (ATCC 12228) and C. freneyi (CIP 52.16) was determined to be 0.32, 0.26, 0.47 and 0.11 mg/mL, respectively. In the time-kill curve study against C. acnes, Acnocure, containing thymol 0.25% and 0.1% Curcuma turmerone as well as thymol 0.1% and 0.1% Curcuma turmerone in a cosmetic simplex formulation, demonstrated rapid bactericidal activity with a 4.7 log reduction at pH 5.5, occurring within just two hours of the study and lasting for over 24 h. The killing efficacy was similar to our cosmetic reference benchmark, Effaclar DUO serum, used in the same study. Additionally, thymol, Curcuma turmerones and Acnocure were evaluated in an anti-inflammatory efficacy assay in lipopolysaccharide (LPS)-primed U937 macrophages model and demonstrated moderate inhibition of interleukin-1β (IL-1β) at 100 µg/mL and significant inhibition of prostaglandin E-2 (PGE-2) at 1 µg/mL, respectively. Further evidence gathered on thymol and Curcuma turmerones in an IL-1α-stimulated dermal fibroblast model showed >90% inhibition of PGE-2 release between 2 µg/mL and 30 µg/mL concentrations. These promising results position Acnocure as a natural alternative for the replacement of synthetic corticosteroids and antibiotics with potent anti-acne skincare properties. Full article

Background: The average fibre consumption of 4–10-year-old children in the UK is 14.6 g per day, with only 14% of these children reaching the 20 g recommended by the SACN (UK Scientific Advisory Committee on Nutrition), and this ‘fibre gap’ may be most pronounced in communities with the lowest socioeconomic status. School breakfast clubs target children from disadvantaged communities, but their provision may favour lower-fibre foods, due to perceptions that children will reject higher-fibre foods. Our research programme aims to increase the fibre density, digestive-metabolic quality and acceptability of school breakfast provision. Methods: In Study 1, we examined the in vitro digestion of four novel bread products, to determine the relationship between fibre content and glucose release profile, and assess their suitability for sustaining school activity. In Study 2, we introduced the Prograins breads, alongside higher-fibre breakfast cereals and fresh fruit, to primary school breakfast clubs. Results: The Prograins bread products yielded lower peaks and more sustained glucose release curves than the ‘standard’ white bread control. Many children liked and chose the intervention foods, and the average fibre content of children’s breakfasts increased. Conclusions: We conclude from this study that nutritious, fibre-rich bread products can be acceptable to children and that higher-fibre breakfast provision is feasible, and we recommend larger-scale intervention and assessment to validate these real-world findings. Full article