Standardization and organoleptic and physicochemical characterization of 15 argentinean propolis

El propóleos es una mezcla de composición química compleja que posee propiedades biológicas de gran interés para fines terapéuticos. Existen distintos tipos de propóleos que difieren en su composición química de acuerdo a su origen botánico. En la actualidad se carece de un estándar de calidad de propóleos. Por esta razón, en este trabajo fueron determinados los caracteres organolépticos, propiedades físico- químicas y el contenido total de compuestos fenólicos y flavonoides de 15 muestras de propóleos recolectadas de diferentes regiones de Chaco, Corrientes, Santiago del Estero y Mendoza, para así brindar una estandarización que permita producir medicamentos de propóleos de seguridad y eficacia demostrable. Se encontró gran variación en las propiedades de los diferentes propóleos estudiados, incluso de aquellos provenientes de una misma región. Los propóleos difirieron principalmente en su contenido de compuestos fenólicos y flavonoides, siendo significativamente superiores en los propóleos originarios de Mendoza, donde la vegetación más abundante pertenece a Populus sp.Propolis is a mixture of complex chemical composition that possesses biological properties of great interest for therapeutic purposes. Different types of propolis exist, which differ in its chemical composition according to its botanical origin. At present, there is not a quality standard for propolis. For this reason, in this work the organoleptic characteristics, the physicochemical properties, the total content of phenolic compounds and the flavonoid composition of 15 samples of propolis collected from different regions of Chaco, Corrientes, Santiago del Estero, and Mendoza were determined, for providing an standardization that allows the production of effective and safe propolis products. It was found great variation in the properties of the different studied propolis, even of those from the same region. Principally, propolis differed in its phenolic and flavonoids content, being significantly higher in propolis from Mendoza, where the most abundant vegetation belongs to Populus sp.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Synergistic bactericidal combinations between gentamicin and chitosan capped ZnO nanoparticles: A promising strategy for repositioning this first-line antibiotic

Gentamicin (GEN), a widely used broad-spectrum antibiotic, faces challenges amid the global emergency of antimicrobial resistance. This study aimed to explore the synergistic effects of zinc oxide nanoparticles (ZnO NPs) in combination with GEN on the bactericidal activity against various bacterial strains. Results showed ZnO NPs with MICs ranging from 0.002 to 1.5 μg/mL, while the precursor salt displayed a MIC range of 48.75–1560 μg/mL. Chitosan (CS)-capped ZnO NPs exhibited even lower MICs than their uncapped counterparts, with the CS-capped synthesized ZnO NPs demonstrating the lowest values. Minimal bactericidal concentrations (MBC) aligned with MIC trends. Combinations of CS-capped synthesized ZnO NPs and GEN proved highly effective, inhibiting bacterial growth at significantly lower concentrations than GEN or ZnO NPs alone. This phenomenon may be attributed to the conformation of CS on the ZnO NPs' surface, enhancing the positive particle surface charge. This possibly facilitates a more effective interaction between ZnO NPs and microorganisms, leading to increased accumulation of zinc and GEN within bacterial cells and an overproduction of reactive oxygen species (ROS). It's crucial to note that, while this study did not specifically involve resistant strains, its primary focus remains on enhancing the overall antimicrobial activity of gentamicin. The research aims to contribute to addressing the global challenge of antimicrobial resistance, recognizing the urgent need for effective strategies to combat this critical issue. The findings, particularly the observed synergy between ZnO NPs and GEN, hold significant implications for repositioning the first-line antibiotic GEN

Preformulation Studies of Novel Menthol Prodrugs with Antiparasitic Activity: Chemical Stability, In Silico, and In Vitro Permeability Assays

Based on the demonstrated and reported trypanocidal, leishmanicidal, and antiplasmodial activities of two menthol prodrugs, it was decided to proceed with preformulation studies, which are of key relevance in the drug discovery process. The aim of this study is to examine the stability and permeability of two new menthol prodrugs with antiparasitic activity. To determine the stability of menthol and its prodrugs, the corresponding studies were carried out in buffered solutions at pH values of 1.2, 5.8, and 7.4 at 37 °C. In silico permeability studies were performed using the free PerMM software and then in vitro permeability studies were performed using a biomimetic artificial membrane (BAM). Permeability studies conducted in silico predicted that both menthol and its prodrugs would pass through biological membranes via flip-flop movement. This prediction was subsequently confirmed by in vitro BAM permeability studies, where it was observed that the menthol prodrugs (1c and 1g) exhibited the highest Papp (apparent permeability) value compared to the parent compound. The study reveals that menthol prodrugs exhibit stability at a pH of 5.8 and possess sufficient in vitro permeability values as preformulation parameters

Magnetic layered double hydroxides with carbamazepine for breast cancer treatment

Current cancer chemotherapy is associated with many side effects and, in some cases, drug resistance, which makes the search for new active molecules and drug delivery strategies imperative. Carbamazepine is an antiepileptic compound that has shown efficacy against breast cancer cell lines. In this study, it was incorporated into layered double hydroxide nanoclays, the percentage of drug loading was increased compared to previous research, and the clays were impregnated with magnetic Fe3O4 nanoparticles. The goal of the magnetic Fe3O4-impregnation was to direct the nanocomposites to the therapeutic target with an external magnetic field. The nanoclay-carbamazepine composites had a carbamazepine loading of 51 %, and the nanoclay-carbamazepine-nanoparticles had a drug loading of 13 % due to the addition of more ingredients. The structure of the composites was analyzed by X-ray diffraction and Scherrer equation, showing a layered double hydroxide organization with crystal sizes of 9–15 nm; from transmission electron microscopy, the final compounds showed a particle size of 97–158 nm, small enough for systemic circulation. In vibrating sample magnetization studies, the composites showed a superparamagnetic behavior with high magnetic saturation (9–17 emu/gr), which should allow a good material attraction by an external magnetic field located near the tumor. In vitro drug release studies were done in Franz cells and measured by UV/Vis spectrophotometry; they showed that carbamazepine release from the nanocomposites responds to the media pH: a good drug release at the lysosome pH and slow release at the blood pH. Finally, the efficacy was tested in vitro in MDA-MB-231 breast cancer cells, and the composites showed an enhanced efficacy in comparison with that produced by the free drug (96 % and 62 % of cell inhibition respectively). Carbamazepine administered with magnetic clays as a carrier is a promising treatment for breast cancer, and further studies should be done to measure the arrival time and the efficacy in vivo

Rate of vision loss in neovascular age-related macular degeneration explored

Purpose To explore decline in visual acuity in patients with neovascular age-related macular degeneration (n-AMD) awaiting intravitreal bevacizumab or ranibizumab treatment following initial diagnosis and after disease reactivation. Methods Retrospective analysis of 74 treatment-naïve patients (84 eyes) in two centers in Córdoba, Argentina. The time between treatment indication and intravitreal injection, and the changes in BCVA produced during this delay were studied in both periods. A linear regression model to search the impact of time on progression visual impairment was conducted. Results In both periods, a significant reduction in vision occurred awaiting intravitreal injection. The longer the delay, the greater the vision loss (R2=0.55 p<0.01) and the less improvement following treatment (Pearson coefficient −0.26). The result of the model shows that the change in vision as a function of initial delay were best described by a polynomic model with a mean loss of 5 letters in the first 3 weeks, a slowdown in the rate of change of VA, and a dependence of visual acuity at the moment of diagnosis . The loss of visual acuity after reactivation shows the same behavior as at the onset of the disease but independent of visual acuity prior to reactivation. Conclusion Visual loss awaiting injection intravitreal antiVEGF is clinically significant and with an asymptotic pattern, with early rapid loss of vision in both the onset of the disease and the reactivation. Initiation of anti-VEGF treatment must be undertaken urgently, as should retreatment of disease activation to reduce visual loss.publishedVersionFil: Real, Juan Pablo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento Farmacia; Argentina.Fil: Real, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.Fil: Granero, Gladys E. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento Farmacia; Argentina.Fil: Granero, Gladys E. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.Fil: Palma, Santiago Daniel. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento Farmacia; Argentina.Fil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.Fil: Juárez, Claudio P. Centro Privado de Ojos Romagosa. Departamento Vitreo-Retinal; Argentina.Fil: Luna Pinto, José D. Centro Privado de Ojos Romagosa. Departamento Vitreo-Retinal; Argentina.Fil: Juárez, Claudio P. Fundación VER; Argentina.Fil: Luna, José D. Fundación VER; Argentina.Fil: De Santis, Mariana O. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas. Instituto de Economía y Finanzas; Argentina.Fil: Kelly, Simón P. Royal Bolton Hospital. Ophthalmology Department; Inglaterra.Otras Ciencias Química

Characterization of the Hydrochlorothiazide: β‑Cyclodextrin Inclusion Complex. Experimental and Theoretical Methods

Hydrochlorothiazide (HCT) is one of the most commonly prescribed antihypertensive drugs. In an attempt to gain an insight into the physicochemical and molecular aspects controlling the complex architecture of native β-cyclodextrin (β-CD) with HCT, we performed multiple-temperature–pH isothermal titration calorimetric measurements of the HCT:β-CD system, together with proton nuclear magnetic resonance spectroscopy (¹H NMR), phase solubility analysis, and molecular modeling methods. The A_L-type diagrams, obtained at different pH values and temperatures, suggested the formation of soluble 1:1 inclusion complexes of β-CD with HCT. The corresponding stability constants (<i>K</i>_1:1) were determined by phase solubility studies and compared with those obtained by ITC, with good agreement between these two techniques being found. The three-dimensional array of the complex was studied by ¹H NMR and molecular modeling methods. Both techniques confirmed the formation of the inclusion complex, with good agreement between the experimental and theoretical techniques regarding the HCT binding mode to β-CD. Also, the forces involved in the association process were determined, both from the thermodynamic parameters obtained by ITC (association enthalpy, binding constant, Gibbs free energy, and entropy) and from energetic decomposition analyses derived from computational methods. We concluded that the formation of the HCT:β-CD complex was enthalpy driven, with the inclusion mode of HCT being highly dependent on its ionization state. In all cases, sustained hydrogen bond interactions with hydroxyl groups of β-CD were identified, with the solvation energy limiting the affinity. Regarding the pH and temperature dependence, lower affinity constants were found at higher HCT ionization states and temperatures

Artificial lipid membrane permeability method for predicting intestinal drug transport: Probing the determining step in the oral absorption of sulfadiazine; Influence of the formation of binary and ternary complexes with cyclodextrins

We propose an in vitro permeability assay by using a modified lipid membrane to predict the in vivo intestinal passive permeability of drugs. Two conditions were tested, one with a gradient pH (pH 5.5-donor/pH 7.4-receptor) and the other with an iso-pH 7.4. The predictability of the method was established by correlating the obtained apparent intestinal permeability coefficients (Papp) and the oral dose fraction absorbed in humans (fa) of 16 drugs with different absorption properties. The Papp values correlated well with the absorption rates under the two conditions and the method showed high predictability and good reproducibility. On the other hand, with this method, we successfully predicted the transport characteristics of oral sulfadiazine (SDZ). Also, the tradeoff between the increase in the solubility of SDZ by its complex formation with cyclodextrins and/or aminoacids and its oral permeability was assessed. Results suggest that SDZ is transported through the gastrointestinal epithelium by passive diffusion in a pH-dependent manner. These results support the classification of SDZ as a high/low borderline permeability compound and are in agreement with the Biopharmaceutics Classification Systems (BCS). This conclusion is consistent with the in vivo pharmacokinetic properties of SDZ.Fil: Delrivo, Alicia. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Aloisio, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Longhi, Marcela Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Granero, Gladys Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentin