Foam-in-Vein: Characterisation of Blood Displacement Efficacy of Liquid Sclerosing Foams.

Sclerotherapy is among the least invasive and most commonly utilised treatment options for varicose veins. Nonetheless, it does not cure varicosities permanently and recurrence rates are of up to 64%. Although sclerosing foams have been extensively characterised with respect to their bench-top properties, such as bubble size distribution and half-life, little is known about their flow behaviour within the venous environment during treatment. Additionally, current methods of foam characterisation do not recapitulate the end-point administration conditions, hindering optimisation of therapeutic efficacy. Here, a therapeutically relevant apparatus has been used to obtain a clinically relevant rheological model of sclerosing foams. This model was then correlated with a therapeutically applicable parameter-i.e., the capability of foams to displace blood within a vein. A pipe viscometry apparatus was employed to obtain a rheological model of 1% polidocanol foams across shear rates of 6 s-1 to 400 s-1. Two different foam formulation techniques (double syringe system and Tessari) and three liquid-to-gas ratios (1:3, 1:4 and 1:5) were investigated. A power-law model was employed on the rheological data to obtain the apparent viscosity of foams. In a separate experiment, a finite volume of foam was injected into a PTFE tube to displace a blood surrogate solution (0.2% w/v carboxymethyl cellulose). The displaced blood surrogate was collected, weighed, and correlated with foam's apparent viscosity. Results showed a decreasing displacement efficacy with foam dryness and injection flowrate. Furthermore, an asymptotic model was formulated that may be used to predict the extent of blood displacement for a given foam formulation and volume. The developed model could guide clinicians in their selection of a foam formulation that exhibits the greatest blood displacement efficacy.

Facile production of quercetin nanoparticles using 3D printed centrifugal flow reactors.

Drug nanocrystals are a delivery system comprised of an active pharmaceutical ingredient, with small amounts of a surface stabilizer. Despite offering simplicity in formulation, their manufacture can be a challenging endeavour; this is especially true when the production is performed using microfluidic devices. Although precipitation within microchannels can lead to issues such as clogging, microfluidics is an appealing manufacturing method as it provides fine control over mixing conditions. This allows production of nanoparticles with a narrower size distribution and greater reproducibility compared to batch methods. To generate microfluidic devices cost effectively, replica moulding techniques are considered the manufacturing standard. Due to its simplicity and relatively low cost, 3D printing has become prevalent at the laboratory scale, especially during iterative development of new devices. A challenge of microfluidic-based methods is that they require specialized equipment and multi-step procedures, making them less accessible to users with no previous experience. In a recent study we developed a 3D printed flow-through reactor, referred to as reactor-in-a-centrifuge (RIAC). It is a simple device designed to fit in a 50 mL tube and actuated using a laboratory centrifuge, which removes the need for specialized instrumentation. The manufacturing capabilities of the RIAC have been already proven, by reproducible production of liposomes and silver nanoparticles. The present work demonstrates the use of RIACs with a straight- and spiral-shaped channel architecture to produce quercetin nanocrystals, with therapeutically relevant size (190-302 nm) and very low size dispersity (polydispersity index, PDI < 0.1). The work focused on evaluating how changes in operational parameters (actuation speed) and formulation components (medium viscosity and stabilizer type), impacted on nanocrystal size and PDI. Under all tested conditions the obtained nanocrystals had a smaller size and narrower size distribution, when compared to those produced with alternative methods. The obtained quercetin nanosuspensions however showed limited stability, which should be addressed in future investigations. The simplicity of the RIAC makes it an appealing technology to research groups, especially in low-resource settings and without prior expertise in microfluidics.

Foam-in-vein: A review of rheological properties and characterization methods for optimization of sclerosing foams.

Varicose veins are chronic venous defects that affect >20% of the population in developed countries. Among potential treatments, sclerotherapy is one of the most commonly used. It involves endovenous injection of a surfactant solution (or foam) in varicose veins, inducing damage to the endothelial layer and subsequent vessel sclerosis. Treatments have proven to be effective in the short-term, however recurrence is reported at rates of up to 64% 5-year post-treatment. Thus, once diagnosed with varicosities there is a high probability of a permanently reduced quality of life. Recently, foam sclerotherapy has become increasingly popular over its liquid counterpart, since foams can treat larger and longer varicosities more effectively, they can be imaged using ultrasound, and require lower amounts of sclerosing agent. In order to minimize recurrence rates however, an investigation of current treatment methods should lead to more effective and long-lasting effects. The literature is populated with studies aimed at characterizing the fundamental physics of aqueous foams; nevertheless, there is a significant need for appropriate product development platforms. Despite successfully capturing the microstructural evolution of aqueous foams, the complexity of current models renders them inadequate for pharmaceutical development. This review article will focus on the physics of foams and the attempts at optimizing them for sclerotherapy. This takes the form of a discussion of the most recent numerical and experimental models, as well as an overview of clinically relevant parameters. This holistic approach could contribute to better foam characterization methods that patients may eventually derive long term benefit from.

A Microfluidic-Based Investigation of Bacterial Attachment in Ureteral Stents.

Obstructions of the ureter lumen can originate from intrinsic or extrinsic factors, such as kidney stones, tumours, or strictures. These can affect the physiological flow of urine from the kidneys to the bladder, potentially causing infection, pain, and kidney failure. To overcome these complications, ureteral stents are often deployed clinically in order to temporarily re-establish urinary flow. Despite their clinical benefits, stents are prone to encrustation and biofilm formation that lead to reduced quality of life for patients; however, the mechanisms underlying the formation of crystalline biofilms in stents are not yet fully understood. In this study, we developed microfluidic-based devices replicating the urodynamic field within different configurations of an occluded and stented ureter. We employed computational fluid dynamic simulations to characterise the flow dynamic field within these models and investigated bacterial attachment (Pseudomonas fluorescens) by means of crystal violet staining and fluorescence microscopy. We identified the presence of hydrodynamic cavities in the vicinity of a ureteric occlusion, which were characterised by low levels of wall shear stress (WSS < 40 mPa), and observed that initiation of bacterial attachment occurred in these specific regions of the stented ureter. Notably, the bacterial coverage area was directly proportional to the number of cavities present in the model. Fluorescence microscopy confirmed that the number density of bacteria was greater within cavities (3 bacteria·mm-2) when compared to side-holes of the stent (1 bacterium·mm-2) or its luminal surface (0.12·bacteria mm-2). These findings informed the design of a novel technological solution against bacterial attachment, which reduces the extent of cavity flow and increases wall shear stress over the stent's surface.