Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells

Abstract

Purpose To study the protection offered by empty liposomes alone against acrolein-induced changes in urothelial cell viability and explored uptake of liposomes by primary (rat) urothelial cells. Methods Acrolein was used as a means to induce cellular damage and reduce urothelial cellular viability. The effect of acrolein or liposomal treatment on cellular proliferation was studied using BrdU assay. Cytokine release was measured after urothelial cells were exposed to acrolein. Temperature dependent uptake study was carried out for fluorescent labeled liposomes using confocal microscopy. Results Liposome pretreatment protected against acrolein-induced decrease in urothelial cell proliferation. Liposomes also significantly affected the acrolein induced cytokine (IFNγ) release offering protection to the urothelial cells against acrolein damage. We also observed a temperature-dependent urothelial uptake of fluorescent-labeled liposomes occurred at 37 °C (but not at 4 °C). Conclusions Empty liposomes alone provide a therapeutic efficacy against acrolein induced changes in urothelial cell viability and may be a promising local therapy for bladder diseases. Hence our preliminary evidence provides support for liposome-therapy for urothelial protection and possible repair.

Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction

“…Liposomal treatment had no toxic effects on its own. It was shown that liposomes increase the survival of urothelial cells exposed to acrolein and that liposomes bound to the cell surface are internalized via an endocytotic process [ 17 ]. The application of BoNT-A was found to result in SNAP-25 cleavage.…”

Intravesical liposome therapy for interstitial cystitis

“…Based on the available evidence, the mechanism of action for empty liposomes in the bladder likely involves a combination of a physical coating on the urothelium, and also a drug‐like action that promotes repair and regeneration of the bladder lining . Findings in an animal model of protamine sulfate injury were supported by the increased proliferation of rat urothelium cells in primary culture after application of sphingomyelin liposomes, and by the liposomes‐mediated reduction of cell death after brief exposure to toxic acrolein . Findings from cultured cells exposed to acrolein were recapitulated after intravesical administration of liposomes in rat bladder injured by acute exposure to protamine sulfate …”

“…Bladder uptake of instilled liposomes was recently investigated by several techniques, including flow cytometry, confocal and electron microscopy . Confocal microscopy showed that fluorescently‐labeled liposomes are taken up by cultured urothelium cells in a temperature/energy‐dependent manner.…”

Past, Present and Future of Chemodenervation with Botulinum Toxin in the Treatment of Overactive Bladder

“…Empty liposomes composed of endogenous lipids have been reported to have therapeutic effect in interstitial cystitis 37 . Ultrastructural and confocal microscopy on cultured urothelial cells showed that bladder uptake of fluorescent liposomes is endocytosis 38 and energy dependent 39 . The cellular uptake of electron dense gold encapsulated liposomes was found to be temperature dependent, indicating a role for energy dependent endocytosis in the uptake of liposomes 38,40 .…”