Perfluorocarbons for the treatment of decompression illness: how to bridge the gap between theory and practice

Abstract

Decompression illness (DCI) is a complex clinical syndrome caused by supersaturation of respiratory gases in blood and tissues after abrupt reduction in ambient pressure. The resulting formation of gas bubbles combined with pulmonary barotrauma leads to venous and arterial gas embolism. Severity of DCI depends on the degree of direct tissue damage caused by growing bubbles or indirect cell injury by impaired oxygen transport, coagulopathy, endothelial dysfunction, and subsequent inflammatory processes. The standard therapy of DCI requires expensive and not ubiquitously accessible hyperbaric chambers, so there is an ongoing search for alternatives. In theory, perfluorocarbons (PFC) are ideal non-recompressive therapeutics, characterized by high solubility of gases. A dual mechanism allows capturing of excess nitrogen and delivery of additional oxygen. Since the 1980s, numerous animal studies have proven significant benefits concerning survival and reduction in DCI symptoms by intravenous application of emulsion-based PFC preparations. However, limited shelf-life, extended organ retention and severe side effects have prevented approval for human usage by regulatory authorities. These negative characteristics are mainly due to emulsifiers, which provide compatibility of PFC to the aqueous medium blood. The encapsulation of PFC with amphiphilic biopolymers, such as albumin, offers a new option to achieve the required biocompatibility avoiding toxic emulsifiers. Recent studies with PFC nanocapsules, which can also be used as artificial oxygen carriers, show promising results. This review summarizes the current state of research concerning DCI pathology and the therapeutic use of PFC including the new generation of non-emulsified formulations based on nanocapsules.

Perfluorocarbon-based oxygen carriers: from physics to physiology

“…The inertness towards oxidation permits the transportation of excess carbon monoxide (CO) from the blood to the lung, and the acceleration of the recovery of CO-venomed haemoglobin [ 47 , 105 , 108 ]. In addition, the washout of nitrogen associated with decompression sickness was proven efficient in terms of avoiding embolism in rabbit, pig and rat models [ 10 , 57 , 63 , 109 ]. Severe nitrogen embolism in rats that underwent simulated diving with fast surfacing could be prevented by infusing albumin-derived PFD oxygen carriers prior to diving [ 64 ].…”

Cavitation‐Inducible Mesoporous Silica–Titania Nanoparticles for Cancer Sonotheranostics

“…[ 31 ] However, the acoustic droplet vaporization at body temperature often causes serious side effects, including ileus and stroke. [ 32 ] Therefore, PFH, which is a biocompatible and chemically inert compound having a transition temperature at 56 °C, was chosen as the gas precursor in this study. In order to obtain PFH@P‐MSTNs, PFH was loaded into the pores of P‐MSTNs using the oil‐in‐water emulsion method.…”

Nanotechnology as a Versatile Tool for 19F-MRI Agent’s Formulation: A Glimpse into the Use of Perfluorinated and Fluorinated Compounds in Nanoparticles

“…After being drawn up by RES, PFC emulsions are diffused back into the blood, where they dissolve in plasma lipids and are carried to the lungs to be expelled out mainly through exhalation by the lungs [56,73,82]. Even though PFC is intrinsically inert, there are reports of severe retention of PFCs in the liver, spleen, and lungs [83][84][85], and the effect of the PFC when stayed too long in vivo or their intracellular fate is currently undetermined [53,86]. In general, nanosystems of size less than 10 nm, exceedingly are devoured by the renal clearance system, 20 to 100 nm by far, is the optimal size range to avoid physiological barriers, 100 to 200 nm particles have extended potential for prolonged circulation, and size greater than 200 nm is retreated almost certainly to spleen and liver and has the possibility for capillary clogging [87].…”

“…There are some excellently written reviews for further reference on PFCs used for oxygen delivery [55,63,73,124,[161][162][163][164], imaging inflammation [48,91,165,166], and cell tracking [65,98,129,[167][168][169]. Refer to the reviews for profound understanding on 19 F MRI used in biomedicine [44,47,56,[170][171][172], PFCs used for various applications [53,74,84,89,[173][174][175][176] and fluorinated compounds including PFCs used for imaging and/or drug delivery [17,24,54,[177][178][179][180][181][182][183]. Being in the tight grip of SARS-CoV-2, PFCs have been proposed as a source of gas exchange in patients in critical conditions and be employed to protect blood cells [184].…”