Polysorbate 80 coated chitosan nanoparticles for delivery of α-melanocyte stimulating hormone analog (NDP-MSH) to the brain reverse cognitive impairment related to neuroinflammation produced by a high-fat diet (HFD).

This study aimed to develop polysorbate 80-coated chitosan nanoparticles (PS80/CS NPs) as a delivery system for improved brain targeting of α-Melanocyte Stimulating Hormone analog (NDP-MSH). Chitosan nanoparticles loaded with NDP-MSH were surface-modified with polysorbate 80 ([NDP-MSH]-PS80/CS NP), which formed a flattened layer on their surface. Nanoparticle preparation involved ionic gelation, followed by characterization using scanning electron microscopy (SEM) for morphology, dynamic light scattering (DLS) for colloidal properties, and ATR-FTIR spectroscopy for structure. Intraperitoneal injection of FITC-PS80/CS NPs and [NDP-MSH]-PS80/CS NP in rats demonstrated their ability to cross the blood-brain barrier, reach the brain, and accumulate in CA1 neurons of the dorsal hippocampus within 2 h. Two experimental models of neuroinflammation were employed with Male Wistar rats: a short-term model involving high-fat diet (HFD) consumption for 5 days followed by an immune stimulus with LPS, and a long-term model involving HFD consumption for 8 weeks. In both models, [NDP-MSH]-PS80/CS NPs could reverse the decreased expression of contextual fear memory induced by the diets. These findings suggest that [NDP-MSH]-PS80/CS NPs offer a promising strategy to overcome the limitations of NDP-MSH regarding pharmacokinetics and enzymatic stability. By facilitating NDP-MSH delivery to the hippocampus, these nanoparticles can potentially mitigate the cognitive impairments associated with HFD consumption and neuroinflammation.

Quantification of rifampicin loaded into inhaled polymeric nanoparticles by reversed phase high-performance liquid chromatography in pulmonary nonphagocytic cellular uptake.

Rifampicin is an antibiotic effective against both Gram-negative and Gram-positive bacteria and is commonly used as a first-line treatment for tuberculosis caused by Mycobacterium tuberculosis. In this study, a reversed-phase high-performance liquid chromatography method was developed and validated to assess rifampicin, either free or combined with ascorbic acid, loaded into chitosan/Tween 80-coated alginate nanoparticles. The method utilized a reversed-phase C18 Restek column with specific chromatographic conditions: a mobile phase of 60 : 40 ratios of methanol/buffer phosphate (pH 7.0), at a flow rate of 0.8 mL min-1, and an injection volume of 15 µL. rifampicin and the internal standard (rifamycin) had retention times of 4.0 and 2.5 min, respectively, and were detected at 334 nm. The method demonstrated the stability of stored samples after freezing-thawing cycles and specificity for rifampicin, even in the presence of degradation products from stress conditions. The high-performance liquid chromatography method was found to be specific, precise, robust, and sensitive. Results indicated that rifampicin accumulation and uptake kinetics varied based on cell type, formulation (free or loaded in nanoparticles), rifampicin concentration, and incubation time. Confocal fluorescence microscopy images supported these findings, showing isothiocyanate fluorescein nanoparticles distribution in different intracellular regions depending on the cell type used. The societal impact of this research lies in its potential to advance the treatment of respiratory infectious diseases, such as tuberculosis, through the development of more effective and specific drug delivery methods. By optimizing the way drugs, particularly rifampicin in this case, interact with lung cells, we aim to achieve greater treatment efficacy and alleviate the overall burden of disease. Furthermore, our study offers novel insights into the intracellular behavior of rifampin from polymeric nanoparticles, paving the way for personalized medicine approaches in the treatment of respiratory infections. This dual focus on social impact and innovation underscores our commitment to improving global health outcomes and addressing pressing public health challenges.

Live attenuated Mycobacterium bovis strains combined with the encapsulated H65 antigen as a vaccine strategy against bovine tuberculosis in a mouse model.

Mycobacterium bovis is an etiological agent of bovine tuberculosis (bTB) that also infects other mammals, including humans. The lack of an effective vaccine for the control of bTB highlights the need for developing new vaccines. In this study, we developed and evaluated an M. bovis strain deleted in the virulence genes phoP, esxA and esxB as a vaccine candidate against bTB in BALBc mice. The evaluated strains were the new live vaccine and BCG, alone or in combination with ncH65vD. The immunogen ncH65vD is a fusion protein H65, encapsulated together with vitamin D3, within the oily body of a nanocapsule composed of an antigen-loading polymeric shell. All vaccines conferred protection against the M. bovis challenge. However, no significant differences were detected among the vaccinated groups regarding bacterial loads in lungs and spleen. Mice vaccinated with the mutant strain plus ncH65vD showed negative Ziehl Neelsen staining of mycobacteria in their lungs, which suggests better control of bacteria replication according to this protection parameter. Consistently, this vaccination scheme showed the highest proportion of CD4 + T cells expressing the protection markers PD-1 and CXCR3 among the vaccinated groups. Correlation studies showed that PD-1 and CXCR3 expression levels in lung-resident CD4 T cells negatively correlated with the number of colony forming units of M. bovis in the lungs of mice. Therefore, the results suggest a link between the presence of PD-1 + and CXCR3 + cells at the site of the immune response against mycobacteria and the level of mycobacterial loads.

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.

Studies of ternary systems of sulfadiazine with Beta-cyclodextrin and aminoacids / Estudios de sistemas ternarios de sulfadiazina con Beta-ciclodextrina y aminoácidos

Introduction: Cyclodextrins (CD), are known to form inclusion complexes with a variety of guest molecules both in solution and in the solid state. This can lead to the alteration of properties of guest molecules. Unfortunately, the complexation efficiency of CD is rather low, and can be enhanced by formation of ternary complexes using aminoacids (AA). Sulfadiazine (SDZ) is an antibiotic with extremely low water solubility which limits its therapeutic applications and bioavailability. Objetives: The aim of this work was to increase the aqueous solubility of SDZ by preparing ternary complexes of this drug with β-cyclodextrin (βCD) and an AA as a third auxiliary substance. Materials y Methods: Complex formation was studied by phase solubility analysis (PSA), nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), thermogravimetric analysis (TG) and scanning electron microscopy (SEM). Results: The apparent stability constants (KC) of the multicomponent complexes were calculated from the solubility diagrams. By the analysis of the NMR spectra, it could be said that the shifts of some protons evidenced the important role of the AA in the formation of multicomponent complexes. Among the AA, Arginine (ARG) proved to have better solubilizing properties for SDZ, reaching an improvement up to 70 times. The use of DSC, TG and SEM suggested the formation of new solid phases between SDZ:βCD:AA. Conclusions: As a result of this research, it was determined that ternary products were more effective in improving drug solubility than the corresponding SDZ:βCD binary system

Introducción: Las ciclodextrinas (CD), son capaces de formar complejos de inclusión con una variedad de moléculas huésped, tanto en solución y en estado sólido, pudiendo producir la modificación de las propiedades de las moléculas huésped. Desafortunadamente, la eficiencia de la formación de complejos con CD es baja, lo cual se puede mejorar mediante la formación de complejos ternarios utilizando aminoácidos (AA). Sulfadiazina (SDZ) es un antibiótico con muy baja solubilidad en agua que limita su biodisponibilidad y sus aplicaciones terapéuticas. Objetivos: El objetivo de este trabajo fue aumentar la solubilidad acuosa de SDZ mediante la preparación de complejos ternarios con β-ciclodextrina (βCD) y un AA como una tercera sustancia. Materiales y Métodos: La formación de complejos se estudió por análisis de solubilidad de fases (PSA), resonancia magnética nuclear (RMN), calorimetría diferencial de barrido (DSC), análisis termogravimétrico (TG) y microscopía electrónica de barrido (SEM). Resultados: Las constantes de estabilidad aparente (KC) de los complejos multi-componentes se calcularon a partir de los diagramas de solubilidad. Por el análisis de los espectros de RMN se constató, por los corrimientos de algunos protones, el papel importante de los AA en la formación de complejos ternarios. Entre los AA, arginina (ARG) demostró tener mejores propiedades de solubilización para SDZ, alcanzando una mejora de hasta 70 veces. El uso de DSC, TG y SEM sugirió la formación de nuevas fases sólidas entre SDZ:βCD:AA