TY - JOUR AB - Background: In 2022, there were an estimated 20 million new cancer cases and 9.7 million deaths. The number of new cancer cases is expected to rise to over 35 million by 2050, marking a 75% increase from 2022 levels. Twenty to eighty-six percent of cancer patients suffer from taste disorders (TD), which are associated with an increased risk of malnutrition. Cachectic syndrome is linked to the presence and growth of tumors and leads to systemic inflammation. Synsepalum dulcificum is a plant whose berries contain miraculin, a glycoprotein that transforms sour tastes into sweet and can ameliorate TD. Objectives: To evaluate the effect of the regular intake of dried miracle berries (DMBs), a novel food containing miraculin, on biomarkers of inflammation and cachexia in malnourished patients with cancer and TD receiving systemic antineoplastic therapy. Methods: we conducted a triple-blind, randomized, placebo-controlled pilot clinical trial. Thirty-one patients with cancer of various etiologies who received chemotherapy were enrolled in this pilot study and divided into three groups. The first group received a tablet containing 150 mg of DMB (standard dose), the high-dose group received a tablet of 300 mg of DMB, and the third group received a tablet with 300 mg of the placebo for three months before each main meal. The plasma levels of several molecules associated with inflammation and cancer cachexia were measured using the X-MAP Luminex multiplexing platform. Results: We found decreased plasma levels of IFN-γ in the standard-dose group. In addition, our results suggest a downtrend of IL-1β levels in the three groups after three months of intervention (p = 0.093). Moreover, the three groups showed a reduction in tumor-derived molecule proteolysis-inducing factor/dermcidin (p = 0.021). It is important to highlight the positive correlation between IL-6 and IL-10 in the standard group, which suggests a better balance between proinflammatory and anti-inflammatory cytokines. Regardless of DMB consumption, soluble TNF receptor type II tended to decrease with treatment in patients who responded well to the antineoplastic treatment (p = 0.011). We did not find significant correlations between cytokines and sensory variables or dietary and nutritional status. Conclusions: Our results suggest that the regular consumption of a standard dose of DMB along with a systemic antineoplastic treatment could contribute to reducing inflammation and cachexia biomarkers in malnourished patients with cancer exhibiting TD. In this sense, nutritional support is crucial in the treatment of cancer cachexia. In our view, it should be considered a coadjuvant of therapeutics. Future studies on the molecular signaling pathways and specific mechanisms of action of bioactive compounds within food supplements, such as miraculin, will allow them to be used to target pathogenic mechanisms of cancer cachexia and malnutrition: NCT05486260. AU - I. Álvarez‐Mercado, A.* AU - López‐Plaza, B.* AU - Plaza‐Díaz, J.* AU - Arcos-Castellanos, L.* AU - Ruiz Ojeda, F.J. AU - Brandimonte-Hernández, M.* AU - Feliú, J.* AU - Hummel, T.* AU - Milla, S.P.* AU - Gil, Á.* C1 - 74715 C2 - 57583 CY - Mdpi Ag, Grosspeteranlage 5, Ch-4052 Basel, Switzerland SP - 622 - 622 TI - Miraculin can contribute to a reduction in inflammatory biomarkers and cachexia in malnourished patients with cancer and taste disorders. JO - Pharmaceuticals VL - 18 IS - 5 PB - Mdpi PY - 2025 SN - 1424-8247 ER - TY - JOUR AB - The nasal epithelium is an important target for drug delivery to the nose and secondary organs such as the brain via the olfactory bulb. For both topical and brain delivery, the targeting of specific nasal regions such as the olfactory epithelium (brain) is essential, yet challenging. In this study, a numerical model was developed to predict the regional dose as mass per surface area (for an inhaled mass of 2.5 mg), which is the biologically most relevant dose metric for drug delivery in the respiratory system. The role of aerosol diameter (particle diameter: 1 nm to 30 µm) and inhalation flow rate (4, 15 and 30 L/min) in optimal drug delivery to the vestibule, nasal valve, olfactory and nasopharynx is assessed. To obtain the highest doses in the olfactory region, we suggest aerosols with a diameter of 20 µm and a medium inlet air flow rate of 15 L/min. High deposition on the olfactory epithelium was also observed for nanoparticles below 1 nm, as was high residence time (slow flow rate of 4 L/min), but the very low mass of 1 nm nanoparticles is prohibitive for most therapeutic applications. Moreover, high flow rates (30 L/min) and larger micro-aerosols lead to highest doses in the vestibule and nasal valve regions. On the other hand, the highest drug doses in the nasopharynx are observed for nano-aerosol (1 nm) and fine microparticles (1-20 µm) with a relatively weak dependence on flow rate. Furthermore, using the 45 different inhalation scenarios generated by numerical models, different machine learning models with five-fold cross-validation are trained to predict the delivered dose and avoid partial differential equation solvers for future predictions. Random forest and gradient boosting models resulted in R2 scores of 0.89 and 0.96, respectively. The aerosol diameter and region of interest are the most important features affecting delivered dose, with an approximate importance of 42% and 47%, respectively. AU - Farnoud, A. AU - Tofighian, H.* AU - Baumann, I.* AU - Ahookhosh, K.* AU - Pourmehran, O.* AU - Cui, X.* AU - Heuveline, V.* AU - Song, C.* AU - Vreugde, S.* AU - Wormald, P.J.* AU - Menden, M.P. AU - Schmid, O. C1 - 67262 C2 - 54202 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Numerical and machine Learning analysis of the parameters affecting the regionally delivered nasal dose of nano- and micro-sized aerosolized drugs. JO - Pharmaceuticals VL - 16 IS - 1 PB - Mdpi PY - 2023 SN - 1424-8247 ER - TY - JOUR AB - The demand for a more efficient and targeted method for intranasal drug delivery has led to sophisticated device design, delivery methods, and aerosol properties. Due to the complex nasal geometry and measurement limitations, numerical modeling is an appropriate approach to simulate the airflow, aerosol dispersion, and deposition for the initial assessment of novel methodologies for better drug delivery. In this study, a CT-based, 3D-printed model of a realistic nasal airway was reconstructed, and airflow pressure, velocity, turbulent kinetic energy (TKE), and aerosol deposition patterns were simultaneously investigated. Different inhalation flowrates (5, 10, 15, 30, and 45 L/min) and aerosol sizes (1, 1.5, 2.5, 3, 6, 15, and 30 µm) were simulated using laminar and SST viscous models, with the results compared and verified by experimental data. The results revealed that from the vestibule to the nasopharynx, the pressure drop was negligible for flow rates of 5, 10, and 15 L/min, while for flow rates of 30 and 40 L/min, a considerable pressure drop was observed by approximately 14 and 10%, respectively. However, from the nasopharynx and trachea, this reduction was approximately 70%. The aerosol deposition fraction alongside the nasal cavities and upper airway showed a significant difference in pattern, dependent on particle size. More than 90% of the initiated particles were deposited in the anterior region, while just under 20% of the injected ultrafine particles were deposited in this area. The turbulent and laminar models showed slightly different values for the deposition fraction and efficiency of drug delivery for ultrafine particles (about 5%); however, the deposition pattern for ultrafine particles was very different. AU - Momeni Larimi, M.* AU - Babamiri, A.* AU - Biglarian, M.* AU - Ramiar, A.* AU - Tabe, R.* AU - Inthavong, K.* AU - Farnoud, A. C1 - 67649 C2 - 53956 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Numerical and experimental analysis of drug inhalation in realistic human upper airway model. JO - Pharmaceuticals VL - 16 IS - 3 PB - Mdpi PY - 2023 SN - 1424-8247 ER -