New micro-hole zone catheter reduces residual urine and mucosal microtrauma in a lower urinary tract model.

Urinary tract infections (UTIs) are the main complication associated with clean intermittent catheterization (CIC) and are facilitated by post-void residual urine and trauma to the mucosa during voiding. The risk of UTI may be diminished by reducing the residual volumes and preventing microtrauma caused by mucosal suction through the eyelets of conventional eyelet catheters (CEC). A new micro-hole zone catheter (MHZC) was developed and tested in an ex vivo porcine lower urinary tract model and in vivo, in pigs, against a CEC. It was shown that, irrespective of the micro-hole diameter, the new catheter ensured increased flowrates and significantly lower residual volumes at the first flow-stop. Furthermore, with a micro-hole diameter of 0.4 mm, mucosal suction was virtually eliminated, regardless of the insertion depth or simulated intra-abdominal pressure mimicking sitting or standing humans. Pressure profile experiments and endoscopy studies indicated that the bladder gradually folds against the drainage tip of the new catheter, without blocking the flow, and, unlike with the CEC, sharp pressure variations and flow-stops did not occur during voiding. The MHZC outperformed the CEC in all tested scenarios and decreased residual volumes, thus potentially decreasing the risk of UTIs.

Improved Performance With the Micro-Hole Zone Intermittent Catheter: A Combined Analysis of 3 Randomized Controlled Studies Comparing the New Catheter Technology With a Conventional Eyelet Catheter.

PURPOSE: To assess the performance of a new urinary intermittent catheter (IC) prototype designed with a micro-hole drainage zone compared to a conventional eyelet catheter (CEC) in terms of flow-stop, bladder emptying, and hematuria. DESIGN: Randomized controlled crossover studies. SUBJECT AND SETTING: The sample comprised 15 male healthy volunteers (HV) and 15 IC users, along with 15 female HV and 15 IC users. The age range was lower for HV participants than for IC users (range: 20-57 years for HV vs 21-82 years for IC users). The study setting was the Department of Urology, located in Rigshospitalet, Copenhagen. METHODS: Number of flow-stop incidents, residual urine volume at first flow-stop (RV1), and dipstick hematuria were measured during and after catheterization by a health care professional (HV) and by self-catheterisation (IC-users). Results from the 3 studies were combined for HV and IC users on RV1 and number of flow-stop incidents but separated on sex. For incidents of hematuria, an effect of underlying condition was assumed, and a combined analysis on sex was performed, separating HV and IC users. RESULTS: When compared to the micro-hole drainage zone design, catheterizations with CEC resulted in a significantly higher mean RV1 (mean difference: 49 mL in males and 32 mL in females, both P < .001) and average number of flow-stop incidents (8 and 21 times more frequent for males and females, respectively, both P < .001). The likelihood for hematuria was 5.84 higher with CEC than with micro-hole drainage hole design, P = .053, during normal micturition in HV postcatheterization. No serious adverse events were reported. CONCLUSION: The micro-hole drainage zone catheter provides IC users fewer premature flow-stops. This design feature reduces modifiable urinary tract infection risk factors, such as residual urine and micro-trauma; additional research is needed to determine its effects on bladder health.

New Intermittent Urinary Micro-Hole Zone Catheter Shows Enhanced Performance in Emptying the Bladder: A Randomised, Controlled Crossover Study.

Urinary tract infections (UTIs) are common and troublesome complications of clean intermittent catheterisation (CIC) in individuals suffering from incomplete bladder emptying, which may exacerbate the underlying disease and lead to hospitalisation. Aside from the design of the intermittent catheter and its handling, a recent review highlighted residual urine as one of several UTI risk factors. A new urinary intermittent catheter with multiple micro-holes has been developed for improved bladder emptying. In a controlled crossover study, adult male CIC users were randomised for a health care professional-led catheterisation with the new micro-hole zone catheter (MHZC) and a conventional eyelet catheter (CEC) in two individual test visits to compare the number of flow-stops and the residual urine at the first flow-stop as co-primary endpoints. In 42 male CIC users, the MHZC resulted in significantly fewer flow-stop episodes compared to the CEC (mean 0.17, 95% CI [0.06, 0.45] vs. mean 1.09, 95% CI [0.75, 1.6], respectively; p < 0.001) and significantly less residual urine at the first flow-stop (mean 5.10 mL, SE [1.14] vs. mean 39.40 mL, SE [9.65], respectively; p < 0.001). No adverse events were observed in this study. The results confirm the enhanced performance of the MHZC compared to a CEC, ensuring an uninterrupted free urine flow with no need to reposition the catheter until the bladder is thoroughly empty.

Imidazolium Chloride Ionic Liquid Mixtures as Separating Agents: Fuel Processing and Azeotrope Breaking.

Relevant chemical separations for the petrochemical and chemical industries include the removal of aromatic hydrocarbons from aliphatics, the desulfurization and denitrification of fuels, and the separation of azeotropic mixtures containing alkanols. In an attempt to contribute to the development of novel technologies, the potentialities of imidazolium chloride ionic liquid (IL) mixtures as separation agents were investigated. Selectivities, capacities, and solvent performance indices were calculated through the activity coefficients at infinite dilution of organic solutes and water in the imidazolium chloride IL: [C8mim]Cl, [C12mim]Cl, and the equimolar mixture of [C4mim]Cl and [C12mim]Cl. Results show that the imidazolium chloride IL might be appropriately tailored for specific purposes, in which an increase in the proportion of cations containing larger alkyl chains tends to increase the overall affinity with organic solutes. The IL designer solvent concept was explored by comparing the IL equimolar mixture results with the intermediary [C8mim]Cl. The COSMO-RS thermodynamic model was also applied, showing it to be a promising tool for a fast qualitative screening of potential separation agents for specific separation processes.

Development of an ex-vivo porcine lower urinary tract model to evaluate the performance of urinary catheters.

Intermittent catheterization is the gold standard method for bladder management in individuals with urinary retention and/or incontinence. It is therefore important to understand the performance of urinary catheters, especially on parameters associated to risks of developing urinary tract infections, and that may impact the quality of life for urinary catheter users. Examples of such parameters include, urine flowrate, occurrence of flow-stops, and residual urine left in the bladder after flow-stop. Reliable in-vitro and/or ex-vivo laboratory models represent a strong asset to assess the performance of urinary catheters, preceding and guiding in-vivo animal studies and/or human clinical studies. Existing laboratory models are generally simplified, covering only portions of the catheterization process, or poorly reflect clinical procedures. In this work, we developed an ex-vivo porcine lower urinary tract model that better reflects the catheterization procedure in humans and allows to investigate the performance of standard of care catheters. The performance of three standard of care catheters was investigated in the developed model showing significant differences in terms of flowrate. No differences were detected in terms of residual volume in the bladder at first flow-stop also when tuning the abdominal pressure to mimic a sitting down and standing up position. A newly discovered phenomenon named hammering was detected and measured. Lastly, mucosal suction was observed and measured in all standard of care catheters, raising the concern for microtrauma during catheterization and a need for new and improved urinary catheter designs. Results obtained with the ex-vivo model were compared to in-vivo studies, highlighting similar concerns.

Long lasting mucoadhesive membrane based on alginate and chitosan for intravaginal drug delivery.

The intravaginal route of administration can be exploited to treat local diseases and for systemic delivery. In this work, we developed an alginate/chitosan membrane sufficiently stable in a simulated vaginal fluid and able to dissolve over time at a very slow and linear rate. The membrane demonstrated good mechanical properties both in its swollen and dry form. As a study case, we evaluated the viability of this potential drug delivery system for the treatment of bacterial vaginosis, a common disease affecting women in their reproductive age. Metronidazole was effectively included in the alginate/chitosan membrane and its bactericide effect was demonstrated against Staphylococcus aureus and Gardnerella vaginalis, simultaneously showing good biocompatibility with a cervix epithelial cell line. Since this alginate/chitosan membrane is stable in a simulated vaginal environment, is easy to fabricate and can be used for the controlled release of a model drug, it represents a promising drug delivery system for local intravaginal applications.

Where Is the Drug? Quantitative 3D Distribution Analyses of Confined Drug-Loaded Polymer Matrices.

To enhance oral bioavailability of poorly soluble drugs, microfabricated devices can be utilized. One example of such devices is microcontainers. These are cylindrical in shape with an inner cavity for drug loading and with only the top side open for release. Supercritical CO2 (scCO2) impregnation is an interesting technique for loading drugs into polymeric matrices in, for example, microcontainers since it avoids the use of organic solvents and is cheap. One of the main drawbacks of this technique is the unknown three-dimensional drug distribution in the polymer matrix. The aim of this study was to investigate the loading of two poorly soluble drugs, naproxen and ketoprofen, by scCO2 impregnation into confined polymer matrices of different sizes. Three different sizes of microcontainers (small, medium, and large) and, thereby, different surface areas accessible for impregnation were compared. From in vitro studies, the amount of naproxen and ketoprofen loaded into the different microcontainers and their corresponding release profiles were seen to be similar. A custom-made Raman microscope facilitated volumetric Raman maps of an entire microcontainer filled with polyvinylpyrrolidone (PVP) and scCO2 impregnated with either naproxen or ketoprofen. In all microcontainer sizes, the drugs were only detected in the top layer of the polymer matrix, explaining the observed similar release profiles. Using X-ray powder diffraction and Raman spectroscopy, the solid state form of the drugs was evaluated, showing that ketoprofen was amorphous in all microcontainer sizes. Naproxen was found not to be crystalline nor amorphous but in a less ordered configuration than the crystalline state. In conclusion, volumetric Raman mapping is a powerful technology for imaging drug distribution and drug crystallinity in polymers and allowed us to conclude that (i) scCO2 impregnation depth does not depend on surface area and (ii) impregnated drugs are noncrystalline.

From concept to in vivo testing: Microcontainers for oral drug delivery.

This work explores the potential of polymeric micrometer sized devices (microcontainers) as oral drug delivery systems (DDS). Arrays of detachable microcontainers (D-MCs) were fabricated on a sacrificial layer to improve the handling and facilitate the collection of individual D-MCs. A model drug, ketoprofen, was loaded into the microcontainers using supercritical CO2 impregnation, followed by deposition of an enteric coating to protect the drug from the harsh gastric environment and to provide a fast release in the intestine. In vitro, in vivo and ex vivo studies were performed to assess the viability of the D-MCs as oral DDS. D-MCs improved the relative oral bioavailability by 180% within 4h, and increased the absorption rate by 2.4 times compared to the control. This work represents a significant step forward in the translation of these devices from laboratory to clinic.

Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils.

Tissue damage caused by excessive amounts of neutrophil-derived reactive oxygen species (ROS) occurs in many inflammatory diseases. Butyrate is a short-chain fatty acid (SCFA) with known anti-inflammatory properties, able to modulate several neutrophil functions. Evidence is provided here that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear as promising tools to limit ROS-dependent tissue injury during inflammation. Particularly, by virtue of their mucoadhesiveness, B-NPs administered by enema can be effective in the treatment of inflammatory bowel diseases.

Scaffolds based on chitosan/pectin thermosensitive hydrogels containing gold nanoparticles.

Thermosensitive hydrogels based on chitosan/pectin (CS/Pec) and CS/Pec/gold nanoparticles (CS/Pec/AuNPs) were successfully prepared with different AuNP levels. Using a tilting method, gelation temperature was demonstrated to decrease when the amount of AuNPs increased and pectin concentrations decreased. The presence of AuNPs in the CS/Pec composite was evaluated via WAXS and UV-vis techniques, while SEM analysis assessed the average size of pores (350-600µm). All samples were extremely cytocompatible with many cell types, such as normal kidney epithelial cells (VERO cells), epithelial colorectal adenocarcinoma cells (HT-29 cells), HPV-16 positive human cervical tumour cells (SiHa cells), kidney epithelial cells (LLCMK2 cells) and murine macrophage cells (J774A1 cells). Cell viability assays using the MTT method upon mouse preosteoblastic cells (MC3T3-E1 cells) showed that CS/Pec and CS/Pec/AuNPs composites had the potential to foster proliferation and growth of bone cells, making them possible stimulators for reconstruction of bone tissues.