In vitro and ex vivo evaluation of the biological performance of sclerosing foams

Abstract

Since the first reports on foam sclerotherapy, multiple studies have been conducted to determine the physical properties and behavior of foams, but relatively little is known about their biological effects on the endothelial cells lining the vessel wall. Moreover, a systematic comparison of the biological performance of foams produced with different methods has not been carried out yet. Herein, a 2D in vitro method was developed to compare efficacy of commercially available polidocanol injectable foam (PEM, Varithena) and physician-compounded foams (PCFs). Endothelial cell attachment upon treatment with foam was quantified as an indicator of therapeutic efficacy, and was correlated with foam physical characteristics and administration conditions. An ex vivo method was also developed to establish the disruption and permeabilisation of the endothelium caused by sclerosing agents. It relied on the quantitation of extravasated bovine serum albumin conjugated to Evans Blue, as an indicator of endothelial permeability. In our series of comparisons, PEM presented a greater overall efficacy compared to PCFs, across the different biological models, which was attributed to its drainage dynamics and gas formulation. This is consistent with earlier studies that indicated superior physical cohesiveness of PEM compared to PCFs.

Development of Glycerol-Rose Bengal-Polidocanol (GRP) foam for enhanced sclerosis of a cyst for cystic diseases

“…The result for which the addition of 10% glycerol improves the foam stability is also comparable to a previous study [37], However, the relationship between the increased foam stability or the added glycerol amount to the foam efficacy or cytotoxicity has not been investigated for kidney cysts. There are reports in which various foams were tested ex vivo, in the venous tissue of patients [38]. However, to investigate in vitro at the cellular level the efficacy of the glycerol and Rose Bengal added GRP foam, a transwell experiment was devised shown later in result 3.…”

“…However, this would fail to mimic the real cystic environment. Many have reported ex vivo experiments using the veins of patients that are removed from their bodies and treated with foam [38]. However, because this study wanted to investigate the sclerosing foams on PKD organ derived cysts, ex vivo experiments using the veins were not deemed a reasonable tool in this study.…”

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

“…Depending on surfactant concentration (Bai et al, 2018), liquid‐to‐gas ratio—also referred to as foam quality in the literature (Cameron et al, 2013), method of production (Carugo et al, 2013; Critello et al, 2017), syringe type and needle size (Bottaro et al, 2019), and bubble size distribution—also referred to as size dispersity in the literature (Cameron et al, 2013; Carugo et al, 2016; Critello et al, 2017); the stability of the resulting foam can vary (Cavezzi & Tessari, 2009). An ideal sclerosing foam needs to be sufficiently cohesive, viscous, and with a low bubble size dispersity in order to exhibit stable characteristics (i.e., lower drainage time and slower rate of coarsening) (Star, Connor, & Parsi, 2018).…”

“…The results of this study demonstrate that the gas composition is not the sole factor responsible for enhanced properties of PEM, but that the production mechanism for Varithena® (see Figure 5) also plays a crucial role in producing a consistent foam microstructure (Carugo et al, 2016). Other studies discuss the effect of needle size (Bottaro, Paterson, Quercia, et al, 2019), liquid‐to‐gas ratio (Cameron et al, 2013), and production techniques (Critello et al, 2017) on bubble‐size distribution. Although these studies explore the microstructural and flow phenomena of sclerosing foams, as well as discussing microstructural differences between PEM and PCFs, there remains a gap in the literature on flow properties of sclerosing foams.…”

“…The physical and chemical attributes of foams such as surfactant formulation and liquid viscosity can be tuned to minimize drainage—the more viscous the liquid phase, the greater the viscous dissipation during drainage, hence the slower the rate of drainage (Saint‐Jalmes, 2006; Saint‐Jalmes & Langevin, 2002). A number of studies provide experimental data that correlate needle size (Bottaro, Paterson, Quercia, et al, 2019), foam type and production technique (Carugo et al, 2016; Critello et al, 2017), surfactant type (Bai et al, 2018) and concentration (Bai et al, 2018; Critello et al, 2017), and liquid‐to‐gas ratio (Cameron et al, 2013) with drainage time.…”