Liposomes for entrapping local anesthetics: A liposome electrokinetic chromatographic study

Abstract

Bupivacaine is a lipophilic, long-acting, amide class local anesthetic commonly used in clinical practice to provide local anesthesia during surgical procedures. Several cases of accidental overdose with cardiac arrest and death have been reported since bupivacaine was introduced to human use. Recent case reports have suggested that Intralipid (Fresenius Kabi) is an effective therapy for cardiac toxicity from high systemic concentrations of, e.g. bupivacaine, even though the mechanism behind the interaction is not fully clear yet. Our long-term aim is to develop a sensitive, efficient, and non-harmful lipid-based formulation to specifically trap harmful substances in vivo. In this study, the in vitro interaction of local anesthetics (bupivacaine, prilocaine, and lidocaine) with Intralipid or lipid vesicles containing phosphatidylglycerol, phosphatidylcholine, cardiolipin, cholesterol, and N-palmitoyl-D-erythro-sphingosine (ceramide) was determined by liposome electrokinetic chromatography. The interactions were evaluated by calculating the retention factors and distribution constants. Atomic force microscopy measurements were carried out to confirm that the interaction mechanism was solely due to interactions between the analytes and the moving pseudostationary phase and not by interactions with a stationary lipid phase adsorbed to the fused-silica wall. The heterogeneity of the liposomes was also studied by atomic force microscopy. The liposome electrokinetic chromatography results demonstrate that there is higher interaction between the drugs and negatively charged liposome dispersion than with the commercial Intralipid dispersion.

Effects of Liposomes Charge on Extending Sciatic Nerve Blockade of N-ethyl Bromide of Lidocaine in Rats

“…There are studies that demonstrate electrostatic interaction between LA and anionic liposomes or lipid tissues. Compared with the commercial neutral lipid emulsion (Intralipid), greater interaction between negatively charged liposomes dispersion and commonly used LA (bupivacaine, prilocaine, and lidocaine) was discovered in an electrokinetic chromatographic study15. Bupivacaine interacts with negatively charged cardiolipin head groups through electrostatic effects16.…”

Effect of ionic liquids on the interaction between liposomes and common wastewater pollutants investigated by capillary electrophoresis

“…In order to determine the interaction between the liposomes and the wastewater compounds we used liposomes comprising zwitterionic phosphatidylcholine (PC; eggPC) and negatively charged phosphatidylglycerol (PG; POPG), with and without cholesterol as additive. It has previously been shown [26] that only negligible amounts of phospholipids, similar to those used in this study, are adsorbed on the fused silica capillary wall and therefore the only major chromatographic interaction mechanism is partitioning of the analytes between the pseudostationary liposome phase and the aqueous phase. Therefore, the retention factors were calculated using Eq.…”

Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats*

“…In spite of the proven efficacy of LE in resuscitating bupivacaine-induced cardiac arrest, the underlying mechanism behind the interaction of LE and bupivacaine is not fully understood. Lipid sink theory was among one of the several mechanisms proposed for the rescue action LE (5;9;10). Based on this theory fat droplets in the blood form lipid compartments or ‘lipid sinks’, into which lipophilic drugs like bupivacaine might dissolve and therefore LE increases the clearance of local anesthetic from the aqueous plasma or cardiac tissue (5).…”