Search Results (28)

Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction in gastrointestinal adverse effects, and insufficient dose flexibility for individualized therapy. In many cases, conventional excipients and release mechanisms remain predominant, leaving drug-specific physicochemical and pharmacokinetic constraints only partially addressed. These gaps highlight the need for a comprehensive synthesis of recent technological advances to guide the development of more effective, patient-centered delivery systems. Methods: A narrative literature review was conducted using Web of Science and PubMed databases to identify original research articles and comprehensive technological studies on oral SR formulations of NSAIDs and paracetamol published between January 2020 and March 2025. Inclusion criteria focused on preclinical and technological research addressing formulation design, excipient innovations, and manufacturing approaches. Results: Sixty-four studies met the inclusion criteria, encompassing polymeric matrices (31%), lipid-based carriers (18%), microspheres/hydrogel beads/interpenetrating polymer networks (30%), nanostructured systems (11%), and hybrid platforms (10%). The most common strategies involved pH-dependent release, mucoadhesive systems, and floating drug delivery, aiming to optimize release kinetics, minimize mucosal irritation, and sustain therapeutic plasma levels. Advances in manufacturing—such as hot-melt extrusion, 3D printing, electrospinning, and spray drying—enabled enhanced control of drug release profiles, improved stability, and in some cases up to 30–50% prolongation of release time or reduction in Cmax fluctuations compared with conventional formulations. Conclusions: Recent formulation strategies show substantial potential to overcome long-standing limitations of SR NSAID delivery, with expected benefits for patient compliance and quality of life through reduced dosing frequency, better tolerability, and more predictable therapeutic effects. Nevertheless, integration of in vitro performance with pharmacokinetic and clinical safety outcomes remains limited, and the translation to clinical practice is still in its early stages. This review provides a comprehensive overview of current technological trends, identifies persisting gaps, and proposes future research directions to advance SR NSAID systems toward safer, more effective, and patient-focused therapy. Full article

Background: Despite advances in gene-targeted and immunotherapies, many aggressive cancers—including glioblastoma and triple-negative breast cancer—remain refractory to treatment. Mounting evidence implicates metabolic reprogramming, especially dysregulation of glucose and glutamine metabolism, as a core hallmark of tumor progression. Natural compounds with metabolic-modulatory effects have emerged as promising adjuncts in oncology. Research Question and Objectives: This review investigates the following question: How can metabolic-targeted therapies—particularly those modulating the Warburg effect and glutamine metabolism—improve cancer treatment outcomes, and what role do natural compounds play in this strategy? The objectives were to (1) evaluate the therapeutic potential of metabolic interventions targeting glucose and glutamine metabolism, (2) assess natural compounds with metabolic regulatory activity, (3) examine integration of metabolic-targeted therapies with conventional treatments, and (4) identify metabolic vulnerabilities in resistant malignancies. Methods: A qualitative systematic review (QualSR) was conducted following PRISMA guidelines. A total of 87 peer-reviewed studies published between 2000 and 2024 were included. Inclusion criteria required clearly defined mechanistic or clinical endpoints and, for clinical trials, sample sizes ≥ 30. Data extraction focused on tumor response, survival, metabolic modulation, and safety profiles. Results: Curcumin significantly reduced serum TNF-α and IL-6 (both p = 0.001) and improved antioxidant capacity (p = 0.001). EGCG downregulated ERα (p = 0.002) and upregulated tumor suppressors p53 and p21 (p = 0.001, p = 0.02). High-dose intravenous vitamin C combined with chemoradiotherapy yielded a 44.4% pathologic complete response rate in rectal cancer. Berberine suppressed Akt/mTOR signaling and glutamine transporter SLC1A5 across tumor types (q < 10⁻¹⁰). However, poor bioavailability (e.g., EGCG t½ = 3.4 ± 0.3 h) and systemic toxicity limit their standalone clinical application. Conclusions: Metabolic-targeted therapies—particularly natural compounds acting on glucose and glutamine pathways—offer a viable adjunct to standard cancer therapies. Clinical translation will require biomarker-driven patient stratification, improved delivery systems, and combination trials to optimize the therapeutic impact in treatment-resistant cancers. Full article

Background: The use of optical microscopic techniques has gained increasing attention in recent years for studying the bioavailability (BA) and bioequivalence (BE) of topical drugs. Stimulated Raman scattering (SRS), one type of optical imaging technique, probes chemical-specific information and has excellent spatiotemporal resolution. It uses intrinsic molecular vibrational signatures, and therefore, labeling samples or other treatments is unnecessary to track a molecule. Because of its unique advantages, studies have used SRS for BA evaluations and, more recently, for BE evaluations. In BE evaluation, low data variance within a treatment group is important to ensure sensitivity and specificity in comparing treatment groups. Methods: When measuring forward-direction SRS signals transmitted through skin, the signal intensity is susceptible to variance due to several factors, such as the microscope system’s performance, the different optical features of topical drug products, and the heterogeneity of skin in transmitting light. This work closely investigated the effects of these factors on an SRS signal and developed solutions to reduce their effects on the data variance. Specifically, we constructed a method using a dual-modality detector built in-house, which simultaneously measured both the SRS signal and total light transmission synchronized in time and co-registered in space. Results: We developed equations to normalize SRS signals using the transmission intensity, and the results demonstrated a clear improvement in the SRS signal via a reduction in the signal variance (up to a 9.46% CV value decrease) that is otherwise caused by various factors associated with the use of topical drugs and the composition of the skin. We carried out an exploratory BE study using tretinoin-containing topical products and observed improvements in BE assessment with the developed method (could achieve a reduction of 0.11 in the CI value). Conclusions: This work has led to a better understanding of the factors that affect SRS imaging and has provided an effective method to compensate for these factors in BE assessments. This is a critical initial effort for better practical implementation of SRS in cutaneous pharmacokinetics (cPKs) studies of topical drugs. Full article

Isotopic investigations focused on determining the mobility and provenance of ancient human civilizations and sourcing of archeological artifacts continue to gain prominence in archeology. Most studies focus on the premise that the geographic variation in isotope systems of interest (e.g., Sr, Pb, Nd, O) in the natural environment is recorded in both human hard tissues of local individuals and raw materials sourced for artifacts within the same region. The introduction of multi-collection–inductively coupled plasma mass spectrometry (MC-ICP-MS) and laser ablation systems are techniques that consume smaller sample sizes compared to previous mass spectrometric approaches due to their higher ionization efficiency and increased sensitivity. This development has facilitated the isotopic measurement of trace elements present at low abundances (e.g., Pb, Nd, <1-to-low ppm range) particularly in human tooth enamel. Accurate interpretation of any isotope ratio measurement for the proveniencing of such low-abundance samples requires the adequate evaluation of post-mortem diagenetic alteration. A synopsis of practices currently in use for identifying post-mortem alteration in human archeological samples is discussed here. Post-mortem shifts in radiogenic isotope signatures resulting from secondary alteration are distinct from those potentially related to the impact of climate change on the bioavailable budgets for these elements. This topic is of interest to the archeological community and discussed here in the context of Holocene-aged samples from burial sites within the Nile River Valley System, and preferred dust source areas from the neighboring Sahara Desert. Full article

Bulgarian wines are renowned worldwide and serve as a symbol of the country. However, ensuring wine authenticity and establishing reliable methods for its assessment are critical challenges in wine quality control. This study investigates the migration of chemical elements within the soil/grape/wine system and utilizes the findings to develop a method for identifying specific elements capable of distinguishing the geographical origin of wine. Additionally, it explores the potential to determine its botanical origin. Thirty monovarietal Bulgarian wines, specifically produced for this study with precisely known geographical and botanical origins, were analyzed for 20 chemical elements. These included macroelements such as Al, B, Ba, Ca, Cu, Fe, K, Mg, Mn, Na, P, Sr, and Zn, as well as microelements like As, Cd, Co, Cr, Li, Ni, and Pb. The study encompassed white wines from Chardonnay, Muscat Ottonel, Sauvignon Blanc, Tamyanka, and Viognier varieties, as well as red wines from Egiodola, Broad-Leaved Melnik, Cabernet, Cabernet Franc, Cabernet Sauvignon, Marselan, Melnik, Merlot, Pinot Noir, and Syrah. The chemical composition was determined in soil extracts (using acetate and EDTA extract to represent the bioavailable fraction), vine leaves, primary musts, and raw wines before clarification and stabilization. Statistically significant correlation coefficients were calculated for the soil/leaves, soil/must, and must/wine systems, enabling an analysis of the migration of chemical elements from soil to wine and the concentration changes throughout the process. The results identified elemental descriptors capable of indicating the geographical origin of wine. Full article

Background: Exogenous melatonin, a nutraceutical for maintaining a healthy sleep–wake cycle and managing sleep disorders, requires large, repeated doses due to its low bioavailability and short half-life. This necessitates the development of a sustained-release formulation with a longer half-life and sustained plasma concentration. Therefore, exogenous novel 5 mg sustained-release melatonin capsules (Melatonin-SR, test product) were formulated. Methods: This open-label cross-over study compared the pharmacokinetics (maximum concentration [C_max], time to reach C_max [T_max], area under the curve [AUC], and elimination half-life [t_1/2]) and the safety of Melatonin-SR with 5 mg immediate-release melatonin capsules (Melatonin-IR, reference product) after single-dose oral administration in healthy fasting adults. Results: Sixteen participants (aged 18–45 years) were randomized (1:1) to receive either Melatonin-SR or Melatonin-IR in two periods with a 7-day washout period. Melatonin-SR reported a lower C_max (11,446.87 pg/mL) compared to Melatonin-IR (22,786.30 pg/mL). The mean T_max of Melatonin-SR and Melatonin-IR was 1.26 h and 0.87 h, respectively. The mean t_1/2 of Melatonin-SR (5.10 h) was prolonged by five-fold compared to Melatonin-IR (1.01 h). One adverse event (vomiting) was reported following the administration of the Melatonin-IR. Conclusions: Melatonin-SR resulted in higher and sustained plasma melatonin concentrations for an extended period and was well-tolerated. Hence, Melatonin-SR may be a promising nutraceutical for maintaining healthy sleep. Full article

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon^®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon^®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20–40 w/w % Kollidon^®SR, 3–7 w/w % chitosan while the auxiliary substances: Aerosil^® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel^® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0–2 h) and the second (2–36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1—the similarity factor, and f2—the factor difference. The results have shown that both Kollidon^®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample. Full article

Four types of non-dairy (plant) drinks—almond, oat, rice, and soy—as well as cow milk with varying fat contents (1.5%, 2.0%, and 3.2%), were examined and compared in terms of the total concentrations of Al, As, B, Ba, Ca, Cd, Cr, Cu, Fe, K, Mg, Na, Mn, Ni, P, Pb, Sb, Se, Sr, and Zn using inductively coupled optical emission spectrometry (ICP OES). Additionally, in vitro gastrointestinal digestion was used to determine the bio-accessible fraction of selected elements, evaluating the nutritional value and risk assessment involved with the consumption of these beverages. A significant difference in the mineral profile was observed depending on the type of plant drink, with the highest content of elements noted in the soy drink and the lowest in the rice drink. Except for Ca and P, the soy drink appears to be a much better source of essential nutrients, including Cu, Fe, and Mn, than cow’s milk. A similar Ca content in plant beverages can be obtained only by adding calcium salt at the stage of its production. Interestingly, by using the multivariate data analysis, the average content of the selected elements (Cu, K, Na, P, and Zn) can be used both to differentiate dairy and non-dairy milk samples according to their type and to distinguish plant drinks from milk of animal origin. The bio-accessibility of essential elements (Ca, Cu, Fe, Mg, Mn, P, Zn) in cow milk was within 8.37–98.2% and increased with an increase in its fat content. Accordingly, by drinking 1 L of this milk daily, it is possible to contribute to the recommended dietary intakes of Ca, P, Cu, Mg, and Zn between 5.6–68%. Although the bio-accessibility of elements in the rice drink was the highest (9.0–90.8%), the soy drink seems to be the best source of nutrients in bioavailable forms; its consumption (1 L/day) covers the requirements of Cu, Mn, Mg, Ca, P, and Zn in 7.0–67%. Unfortunately, both groups of beverages are not important sources of Fe (plant drink) and Mn or Fe (cow milk) in the human diet. On the other hand, potentially toxic elements (Al, B, Ba) were found in them in a relatively inert form. Full article

During the last forty years, the use of strontium isotopes in archaeology and biogeochemical research has spread widely. These isotopes, alone or in combination with others, can contribute to trace past and present environmental conditions. However, the interpretation of the isotopic values of strontium is not always simple and requires good knowledge of geochemistry and geology. This short paper on the use of strontium isotopes is aimed at those who use this tool (archaeologists, but not only) but who do not have a thorough knowledge of mineralogy, geology, and geochemistry necessary for a good understanding of natural processes involving these isotopes. We report basic knowledge and suggestions for the correct use of these isotopes. The isotopic characteristics of bio-assimilable strontium depend not so much on the isotopic characteristics of the bulk rock as, rather, on those of its more soluble minerals. Before studying human, animal and plant remains, the state of conservation and any conditions of isotopic pollution should be carefully checked. Samples should be collected according to random sampling rules. The data should be treated by a statistical approach. To make comparisons between different areas, it should be borne in mind that the study of current soils can be misleading since the mineralogical modification of soil over time can be very rapid. Full article

The growth of the aquafeed sector is highly dependent upon the availability of fish feed with a balanced nutritional composition. The use of prebiotics and probiotics can be an effective solution to increase the bioavailability of feed components. In this study, we evaluated the effect of dietary supplementation with β-propeller phytase (0, 600, 1200, 1800 and 2400 U/kg) from Bacillus and mannan oligosaccharide (MOS) (0, 2, 4 and 8 g/kg) on growth performance and nutrient digestibility of Nile tilapia over 45 days. The findings showed that adding phytase significantly (p < 0.05) increases the growth performance and nutrient digestibility; the 1200 and 1800 U/kg PHY levels showed the maximum weight gain (WG), specific growth rate (SGR) and protein efficiency ratio (PER) and best feed conversion ratio (FCR). Furthermore, phytase increases carcass mineral composition (phosphate and calcium). At the end of the experiment, there were no significant differences among all feeding groups in survival rates (above 90%). Regarding MOS inclusion, insignificant differences were seen in WG, SGR and SR. However, significant effects of MOS were observed on FCR, feed intake (FI) and PER when supplemented at 4 and 8 g/kg of feed. Taken together, our results suggest that supplementation of Nile tilapia feed with adequate amounts of β-propeller phytase from Bacillus and MOS increases growth performance and nutrient digestibility. Full article

Oral and parenteral delivery routes of valproic acid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in the brain. A GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in humans. HSPiP software 5.4.08 predicted excipients with maximum possible miscibility of the drug. Based on the GastroPlus and HSPiP program, various excipients were screened for experimental solubility, nanoemulsions, and respective gel studies intended for nasal-to-brain delivery. These were characterized by size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Results showed that in vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively, from both tablets (IR and SR) at 8 h using GastroPlus. The predicted drug access to the portal vein was substantially higher in IR (115 mg) compared to SR (82.6 mg). The plasma drug concentration–time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime sites of the drug absorption and no effect of nanonization on T_max for sustained release formulation. Hansen parameters suggested a suitable selection of excipients. The program recommended nasal-to-brain delivery of the drug using a cationic mucoadhesive nanoemulsion. The optimized CVE6 was associated with the optimal size (113 nm), low PDI (polydispersity index) (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7% w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. A penetration study using confocal laser scanning microscopy (CLSM) executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6. This might be attributed to the electrostatic interaction existing between the mucosal membrane and nanoglobules. Thus, cationic nanoemulsions and respective mucoadhesive gels are promising strategies for the delivery of VA to the brain through intransal administration for the treatment of seizures and convulsions. Full article

This paper presents an assessment of the effect of various reagents on the qualitative indicators of anti-deflationary single-species sowing phytocenosis on enrichment waste from rare earth ores. It has been established that tailings of loparite ores are not suitable for biological reclamation due to low values of hygroscopic moisture (0.54–2.85%) and clay particles (17.6 ± 0.6%) and high content of bioavailable forms of aluminum (504 ± 14 mg/kg). Seeds of red fescue (Festuca rubra L.) were grown on the tailings of loparite ore enrichment with the addition of opoka (O), brucite (B), and vermiculite (V). The quality of the seed cenosis was assessed by the dry biomass of the above-ground parts of the plants and the plant height. A positive effect (one-way ANOVA followed by Tukey’s HSD test (p < 0.05 and p < 0.01)) of the considered combinations of reagents on the growth of above-ground biomass from 31.5% (V) to 70.3 (V + O), 82.4% (V + B), and 81.8% (V + O+B) and on plant height from 53.8% (V) up to 78.6 (V + O), 83.8% (V + B), and 75.4% (V + O+B) was revealed. The use of a combination of V + O and V + B reagents made it possible to significantly reduce the content of Al (by 19.0% and 52.8%), Sr (by 16.5% and 12.9%), La (by 65.2% and 40.6%), and Ce (by 66.8% and 41.9%) in the aerial part of the sowing phytocenosis compared to control. The results obtained here can become the basis for development of a combined sorption technology for the reclamation of technogenically disturbed lands. Full article

Bisphosphonate (BP) agents have attracted much attention for their precise therapy in some skeletal maladies demonstrated by enhancing osteoclast-mediated bone resorption. In this work, the use of CAM-B3LYP/6-311+G(d,p)/LANL2DZ to estimate the susceptibility of single-walled carbon nanotube (SWCNT) for adsorbing alendronate, ibandronate, neridronate, and pamidronate chelated to two metal cations of 2Mg²⁺, 2Ca²⁺, and 2Sr²⁺ through nuclear magnetic resonance and thermodynamic parameters has been accomplished. For most biological medications, oral bioavailability is too low to reach a therapeutic level, and advanced delivery systems such as formulations including permeation enhancers or enzyme inhibitors, lipid-based nanocarriers, and microneedles will likely increase the oral bioavailability of these medications properly. Therefore, the measurements have described that the eventuality of using SWCNT and BP agents becomes the norm in metal chelating of the drug delivery system, which has been selected through (alendronate, ibandronate, neridronate, pamidronate) → 2X (X = Mg²⁺/Ca²⁺/Sr²⁺) complexes. The NMR results of chelated alendronate, ibandronate, neridronate, and pamidronate complexes adsorbed onto (5,5) armchair SWCNT have remarked the location of active sites of tagged nitrogen (N), phosphorus (S), oxygen (O), and metal cations of magnesium (Mg²⁺), calcium (Ca²⁺), and strontium (Sr²⁺) in these molecules which replace the movement of the charge electron transfer in polar bisphosphonates (BPs) toward (5,5) armchair carbon nanotube (CNT). The thermodynamic results have exhibited that the substitution of 2Ca²⁺ cation by 2Sr²⁺ cation in the compound of the bioactive glasses can be efficient for treating vertebral complex fractures. However, the most fluctuation in the Gibbs free energy for BPs → 2Sr²⁺ has been observed at 300 K. This manuscript aimed to show that (5,5) armchair SWCNT can easily penetrate in the bone cells, delivering chelated BP–cations directly to the bone tissue. Drug delivery systems can improve the pharmacological profile, therapeutic profile, and efficacy of BP drugs and lower the occurrence of off-targets. Full article

The objective of this study was to investigate the impact of Lycopene and L-Carnitine, individually or in combination, on various physiological and molecular factors related to intestinal health and absorption ability in Roosters, such as intestinal morphology, serum biochemical parameters, genes involved in Lycopene uptake, nutritional transport genes, and tight junction genes. The findings of the study revealed that the combination of L-Carnitine and Lycopene supplementation had been found to increase the serum concentration levels of TP and ALB. Interestingly, the relative mRNA expression of genes responsible for Lycopene uptakes, such as SR-BI and BCO2, was higher in the LC group compared to other groups. Additionally, the expression of specific nutritional transport genes in the duodenum was significantly affected by both CAR and LC supplementation groups. The tight junction gene OCLN showed a significant increase in expression in the combination group compared to using either Lycopene or L-Carnitine alone. This study concludes that using Lycopene and L-carnitine in combination in poultry feed can potentially improve intestinal morphology and serum biochemical parameters, increase Lycopene bioavailability, improve nutrients uptake, and enhance the integrity of duodenal tight junctions in Roosters. Full article

Soy-based beverages are one of the most consumed plant-based beverages, which have been used as a substitute for dairy products. Soy is a source of several nutrients (vitamins, minerals, and phenolic compounds, etc.) and its consumption is usually associated with several benefits, such as the prevention of cardiovascular diseases, cancer, and osteoporosis. However, non-essential trace elements can be found in these beverages. Thus, a comprehensive study concerning trace elements Al, As, Cd, Co, Cr, Cu, Fe, Li, Mn, Ni, Pb, Sb, Se, Sn, Sr, and Zn in soy-based beverages was proposed. In vitro digestion allowed to simulate the gastrointestinal juice (bioaccessibility) and the Caco-2 cells culture model was applied for the bioavailability assay. Trace elements measures were performed by inductively coupled plasma optical emission spectrometry (ICP OES). Multivariate analysis classified soy-based beverages according to their soy source (isolate protein, hydrosoluble extract, and beans); Al, Cu, Fe, Mn, Sr, Se, and Zn bioaccessible fractions corresponded to approximately 40%-80% of their total content, and soy-based beverages were found to be a good Fe, Se, and Zn source. However, our results showed risk exposure assessment from daily consumption of one glass of soy-based beverage can contribute to 3.5% and 0.9% of Al Provisional Tolerable Weekly Intake (PTWI) for children and adults, respectively. Full article