Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin.

Thermosensitive chitosan hydrogels-renewable, biocompatible materials-have many applications as injectable biomaterials for localized drug delivery in the treatment of a variety of diseases. To combat infections such as Staphylococcus aureus osteomyelitis, localized antibiotic delivery would allow for higher doses at the site of infection without the risks associated with traditional antibiotic regimens. Fosfomycin, a small antibiotic in its own class, was loaded into a chitosan hydrogel system with varied beta-glycerol phosphate (ß-GP) and fosfomycin (FOS) concentrations. The purpose of this study was to elucidate the interactions between FOS and chitosan hydrogel. The Kirby Bauer assay revealed an unexpected concentration-dependent inhibition of S. aureus, with reduced efficacy at the high FOS concentration but only at the low ß-GP concentration. No effect of FOS concentration was observed for the planktonic assay. Rheological testing revealed that increasing ß-GP concentration increased the storage modulus while decreasing gelation temperature. NMR showed that FOS was removed from the liquid portion of the hydrogel by reaction over 12 h. SEM and FTIR confirmed gels degraded and released organophosphates over 5 days. This work provides insight into the physicochemical interactions between fosfomycin and chitosan hydrogel systems and informs selection of biomaterial components for improving infection treatment.

Autoclaving of Poloxamer 407 hydrogel and its use as a drug delivery vehicle.

With antibiotic-resistant bacteria becoming increasingly prevalent, biomaterials capable of targeted, in situ drug delivery are urgently needed. The synthetic polymer Poloxamer 407 (P407) is of particular interest due to its thermoreversible gelation. Clinical use of P407 typically involves sterilization via autoclaving, but the effects of these extreme environmental conditions on hydrogel water content, rheological properties and efficacy as a drug delivery vehicle remain unknown. The aim of this study was to investigate the effects of autoclaving on the properties of P407 hydrogel. Autoclaving reduced hydrogel water content due to evaporation, thus increasing the polymer weight fraction of the hydrogels. In contrast, except for a reduction in gelation temperature following autoclaving, autoclaved hydrogels had similar rheological properties as nonautoclaved hydrogels. In vitro, autoclaving did not hinder the hydrogel's efficacy as a carrier for vancomycin antibiotic, and P407 (with and without vancomycin) had a bactericidal effect on planktonic Staphylococcus aureus. An in vivo pilot study using P407 to deliver bacteriophage highlighted the need for additional understanding of the functionality of the hydrogel for surgical applications. In conclusion, P407 hydrogel water content and gelation temperature were reduced by autoclave sterilization, while other rheological properties and the efficacy of the biomaterial as a delivery vehicle for vancomycin in vitro were unaffected.

A microfluidic device to study cancer metastasis under chronic and intermittent hypoxia.

Metastatic cancer cells must traverse a microenvironment ranging from extremely hypoxic, within the tumor, to highly oxygenated, within the host's vasculature. Tumor hypoxia can be further characterized by regions of both chronic and intermittent hypoxia. We present the design and characterization of a microfluidic device that can simultaneously mimic the oxygenation conditions observed within the tumor and model the cell migration and intravasation processes. This device can generate spatial oxygen gradients of chronic hypoxia and produce dynamically changing hypoxic microenvironments in long-term culture of cancer cells.

Sugar acetates as CO2-philes: molecular interactions and structure aspects from absorption measurement using quartz crystal microbalance.

Sugar acetates, recognized as attractive CO(2)-philic compounds, have potential uses as pharmaceutical excipients, controlled release agents, and surfactants for microemulsion systems in CO(2)-based processes. This study focuses on the quantitative examination of absorption of high pressure CO(2) into these sugar derivatives using quartz crystal microbalance (QCM) as a detector. In addition to the absorption measurement, the QCM is initially found to be able to detect the CO(2)-induced deliquescence of sugar acetates, and the CO(2) pressure at which the deliquescence happens depends on several influencing factors such as the temperature and thickness of the film. The CO(2) absorption in alpha-D-glucose pentaacetate (Ac-alpha-GLU) is revealed to be of an order of magnitude larger in comparison with its anomer Ac-beta-GLU, whereas alpha-D-galactose pentaacetate (Ac-alpha-GAL) absorbs CO(2) less than Ac-alpha-GLU due to the steric-hindrance between the acetyl groups on the anomeric and C4 carbons, implying the significant importance of the molecular structure and configuration of sugar acetates on the absorption. The effects of molecular size and acetyl number of sugar acetates on the CO(2) absorption are evaluated and the results indicate that the conformation and packing of crystalline sugar acetate as well as the accessibility of the acetyls are also vital for the absorption of CO(2). It is additionally found that a CO(2)-induced change in the structure from a crystalline system to an amorphous system results in an order of magnitude increase in CO(2) absorption. Further investigation illustrates the interaction strength between sugar acetates and CO(2) by calculating the thermodynamic parameters such as Henry's law constant, enthalpy and entropy of dissolution from the determined CO(2) absorption. Experiments and calculations demonstrate that sugar acetates exhibit high CO(2) absorption, as at least comparable to ionic liquids. Since the ionic liquids have potential uses in the separation of acidic gases, it is evident from this study that sugar acetates could be used as possible materials for CO(2) separation.

Quartz crystal microbalance (QCM) in high-pressure carbon dioxide (CO2): experimental aspects of QCM theory and CO2 adsorption.

The quartz crystal microbalance (QCM) technique has been developed into a powerful tool for the study of solid-fluid interfaces. This study focuses on the applications of QCM in high-pressure carbon dioxide (CO2) systems. Frequency responses of six QCM crystals with different electrode materials (silver or gold) and roughness values were determined in helium, nitrogen, and carbon dioxide at 35-40 degrees C and at elevated pressures up to 3200 psi. The goal is to experimentally examine the applicability of the traditional QCM theory in high-pressure systems and determine the adsorption of CO2 on the metal surfaces. A new QCM calculation approach was formulated to consider the surface roughness contribution to the frequency shift. It was found that the frequency-roughness correlation factor, Cr, in the new model was critical to the accurate calculation of mass changes on the crystal surface. Experiments and calculations demonstrated that the adsorption (or condensation) of gaseous and supercritical CO2 onto the silver and gold surfaces was as high as 3.6 microg cm(-2) at 40 degrees C when the CO2 densities are lower than 0.85 g cm(-3). The utilization of QCM crystals with different roughness in determining the adsorption of CO2 is also discussed.