The transport barrier in intraperitoneal therapy

Abstract

The peritoneal cavity is important in clinical medicine because of its use as a portal of entry for drugs utilized in regional chemotherapy and as a means of dialysis for anephric patients. The barrier between the therapeutic solution in the cavity and the plasma does not correspond to the classic semipermeable membrane but instead is a complex structure of cells, extracellular matrix, and blood microvessels in the surrounding tissue. New research on the nature of the capillary barrier and on the orderly array of extracellular matrix molecules has provided insights into the physiological basis of osmosis and the alterations in transport that result from infusion of large volumes of fluid. The anatomic peritoneum is highly permeable to water, small solutes, and proteins and therefore is not a physical barrier. However, the cells of the mesothelium play an essential role in the immune response in the cavity and produce cytokines and chemokines in response to contact with noncompatible solutions. The process of inflammation, which depends on the interaction of mesothelial, interstitial, and endothelial cells, ultimately leads to angiogenesis and fibrosis and the functional alteration of the barrier. New animal models, such as the transgenic mouse, will accelerate the discovery of methods to preserve the functional peritoneal barrier.

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis — Mission possible?

“…The first layer is comprised of mesothelial cells interconnected by tight junctions, which secrete surface hyaluronan as depicted in Figure 1A. The mesothelial layer functions as a barrier that protects from physical damage and surface adhesion [7]. A submesothelial basement membrane separates the mesothelial layer from the interstitial space, which contains fibroblasts, collagen and other molecules as a first "defense line" against macromolecules ( Figure 1A).…”

“…It is hypothesized that different factors play an important role in the formation of the ascites fluid, such as lymphatic obstruction and osmotic water transport following the leakage of proteins from microcapillaries into the peritoneal cavity [11]. Interestingly, it has been shown that the peritoneal membrane does not correspond to the classic semi-permeable model, but rather is highly permeable to both water, small solutes and proteins [7].…”

“…In fact, the peritoneal membrane does not represent a substantial physical barrier for IP administered low-molecular weight drugs, indicating that small chemotherapeutics can easily redistribute to the systemic circulation [7,12,13]. There is no consensus, however, as to which extent the peritoneal membrane poses a barrier to nano-or micrometer sized particles.…”

Growing a peritoneal dialysis program: A single‐center experience

“…[39][40][41] UF failure may be due to causes other than peritoneal membrane dysfunction. Dietary indiscretion, excessive sodium and fl uid intake, inadequate dialysis prescription, loss of RRF without adjustments in dialysis prescription, and catheter malfunction are often the causes of chronic volume expansion.…”

Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule

“…Previous models in the area of peritoneal transport include pharmacokinetic compartmental models describing the transport processes occurring during peritoneal dialysis (Flessner et al, 1984;Stachowska-Pietka et al, 2006) and peritoneal chemotherapy (Flessner, 2005;Shah et al, 2009). Additionally, a theoretical model describing the IP transport of cisplatin was created (El-Kareh & Secomb, 2004) but no convective transport was taken into account.…”