Drug delivery systems for potential treatment in intracellular bacterial infections

Despite the advent of a considerable number of new antibiotics, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The antibiotic concentration in those specialized niches are often subtherapeutic, for which high doses of antibiotics must often be used. This is not only costly but may also increase localized or systemic side effects. There is therefore an urgent need for materials and methods to enable clinicians to achieve therapeutically effective intracellular concentration of those antibiotics which show good efficiency in vitro. In this setting, the possible use of drug delivery systems (DDS) loaded with antibiotics that exhibit a high in vitro bactericidal activity deserves to be considered. Entrapping or encapsulating the drug within a delivery system provides a greater control of the pharmacokinetic behavior of the active molecule. This more efficient use of antibiotics may diminish their drawbacks and provide the basis for shortening the current time required by classical treatments. This review will focus on the role of DDS as a potential tool against intracellular bacteria

Drug delivery systems for potential treatment of intracellular bacterial infections.

Despite the advent of a considerable number of new antibiotics, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The antibiotic concentration in those specialized niches are often subtherapeutic, for which high doses of antibiotics must often be used. This is not only costly but may also increase localized or systemic side effects. There is therefore an urgent need for materials and methods to enable clinicians to achieve therapeutically effective intracellular concentration of those antibiotics which show good efficiency in vitro. In this setting, the possible use of drug delivery systems (DDS) loaded with antibiotics that exhibit a high in vitro bactericidal activity deserves to be considered. Entrapping or encapsulating the drug within a delivery system provides a greater control of the pharmacokinetic behavior of the active molecule. This more efficient use of antibiotics may diminish their drawbacks and provide the basis for shortening the current time required by classical treatments. This review will focus on the role of DDS as a potential tool against intracellular bacteria

Modeling the influence of MgSO4 invariant points on multiphase reactive transport process during saline soil evaporation

In the present work, we modeled a laboratory experiment where a sand column saturated with a MgSO4 solution is subject to evaporation. We used a compositional formulation capable of representing the effect of geochemistry on flow and transport for concentrated solutions under extreme dry conditions. The model accounts for the water sink/sources terms due to hydrated mineral dissolution/precipitation and the occurrence of invariant points, which prescribe the water activity. Results show that the occurrence of the invariant points at the top of the domain could affect the vapor flux at the column top and salt precipitation along the column. In fact, the invariant points occurrence could explain the spatial fluctuation on the salt precipitates formation. Results also suggest that the complex hydrochemical interactions occurring during soil salinization, including osmotic effects, are crucial not only to understand the salt precipitation, but also the evaporation rate.Fil: Gamazo, P.. Universidad de la Republica; Uruguay. Universidad Politecnica de Catalunya; EspañaFil: Saaltink, M. W.. Universidad Politecnica de Catalunya; EspañaFil: Carrera, J.. Instituto de Diagnóstico Ambiental y Estudios del Agua; EspañaFil: Slooten, L. J.. Instituto de Diagnóstico Ambiental y Estudios del Agua; EspañaFil: Bea, Sergio Andrés. Universidad Nacional del Centro de la Provincia de Buenos Aires. Rectorado. Instituto de Hidrología de Llanuras - Sede Azul; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil; ArgentinaFil: Gran, M.. Universidad Politecnica de Catalunya; Españ

Comparison of antibacterial activity and cytotoxicity of silver nanoparticles and silver-loaded montmorillonite and saponite

Although silver nanoparticles are known for their antibacterial activity, little research has been carried out on what synthesis method provides the most effective particles. In this study, silver nanoparticles were synthesised via chemical reduction by using silver nitrate as the silver precursor, ascorbic acid as the reducing agent and sodium citrate as the stabilising agent. The solutions were adjusted to several pH values employing sodium hydroxide, citric acid or nitric acid. Dynamic light scattering and absorption spectra in the ultraviolet/visible region characterisation revealed that employing nitric acid to adjust the pH produced more varied and larger silver particle sizes. Then, silver nanoparticles were supported on montmorillonite and saponite through wet impregnation or ion exchange methods. Scanning electron microscopy, energy-dispersive X-ray spectroscopy and transmission electron microscopy characterisation confirmed that silver nanoparticles were successfully loaded onto the clay minerals. Next, the antibacterial activity of the samples was evaluated against Escherichia coli and Staphylococcus aureus by determining their minimum inhibitory concentrations and minimum bactericidal concentrations. The free silver nanoparticles did not show any antibacterial activity at 125 mg/L. In contrast, the silver-loaded samples obtained by wet impregnation and with a higher silver content displayed the strongest antibacterial effect. Finally, the cytotoxicity of the samples was determined in GM07492-A cell line by using an XTT colorimetric assay. The calculated IC50 values revealed that the supported silver nanoparticles were barely toxic. Thus, the silver-loaded clay minerals obtained here are promising antibacterial materials with a high-grade safety profile

Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation

The mechanisms that underlie the potent Th1-adjuvant capacity of poly(methyl vinyl ether-co-maleic anhydride) nanoparticles (NPs) were investigated. Traditionally, polymer NPs have been considered delivery systems that promote a closer interaction between antigen and antigen-presenting cells (APCs). Our results revealed that poly(anhydride) NPs also act as agonists of various Toll-like receptors (TLRs) (TLR2, -4, and -5), triggering a Th1-profile cytokine release (gamma interferon [IFN- ], 478 pg/ml versus 39.6 pg/ml from negative control; interleukin-12 [IL-12], 40 pg/ml versus 7.2 pg/ml from negative control) and, after incubation with dendritic cells, inducing a 2.5- to 3.5-fold increase of CD54 and CD86 costimulatory molecule expression. Furthermore, in vivo studies suggest that NPs actively elicit a CD8 T-cell response. Immunization with empty NPs resulted in a significant delay in the mean survival date (from day 7 until day 23 postchallenge) and a protection level of 30% after challenge against a lethal dose of Salmonella enterica serovar Enteritidis. Taken together, our results provide a better understanding of how NPs act as active Th1 adjuvants in immunoprophylaxis and immunotherapy through TLR exploitation

Humoral immune response in hens naturally infected with Salmonella Enteritidis against outer membrane proteins and other surface structural antigens

A simple procedure for obtaining surface exposed antigens of Salmonella Enteritidis is described. A heat treatment of whole bacteria in saline solution induced the release of small membrane vesicles containing outer membrane components as well as surface appendage components, such as fimbriae and flagellin. The characterization of the structural components of this extract, called HE, was established by SDS-PAGE and immunoblotting using polyclonal and monoclonal specific antibodies. Five major groups of proteins were identified: flagellin, porins, OmpA, SEF21 and SEF14 fimbriae. The immunogenicity of these proteins was studied by immunoblotting with serum samples from naturally infected hens. Flagellin, porins, OmpA, SEF14 and SEF21 fimbriae were immunogenic in the S. Enteritidis infected hens (frequency of reactants: 47.3, 97.3, 64.7, 50.0 and 60.8%, respectively); porins also reacted with sera from non infected hens (66.7%). The immunogenicity of these antigens in infected birds provide promise that they may serve as components of an effective subcellular vaccine for poultry salmonellosis

Nanoparticulate adjuvants and delivery systems for allergen immunotherapy

In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines