Bladder Instillation of Liposomes for Bladder Coating and Drug Delivery Platform

Abstract

The clinical use of exogenous polysaccharides for the treatment of interstitial cystitis (IC) has lent credence to the concept of a dysfunctional urothelium as the cause of lower urinary tract symptoms (LUTS). Studies have shown that lipids in the apical membrane of the urothelium form an integral component of the permeability barrier in the bladder. This premise is supported by the therapeutic effect of empty liposomes in the irritated bladder. Instillation of liposomes comprised of natural phospholipids can augment bladder barrier function and support repair following injury from protamine sulfate and irritation with high potassium concentration. The mechanism of action proposed for the therapeutic effect of empty liposomes is that liposomes form a coat on the injured urothelium and block irritation of submucosal afferent nerves. Reduced afferent excitation after liposome instillation is reflected in prolonged intercontractile interval in cystometry. Liposomes offer a powerful new treatment option for IC using an intravesical route and as a platform for intravesical drug delivery.

Potential Orphan Drug Therapy of Intravesical Liposomal Onabotulinumtoxin-A for Ketamine-Induced Cystitis by Mucosal Protection and Anti-inflammation in a Rat Model

“…Tyagi et al . reported that liposomes instilled in a rat’s bladder formed a coating on the urothelium surface and blocked the irritation of the submucosal afferents 24 . Thus, this liposome coating may cover the injured urothelium and block the direct toxic damage induced by ketamine and its metabolites on the bladder of ketamine/Lipotoxin-treated rats.…”

“…Our results reveal sparse suburothelial hemorrhage, improved urothelial tight junction and adhesion protein damage, and less substance P spread in the bladder of rats in the ketamine/Lipotoxin group. Liposomes have been reported to protect the bladder from irritating urine solutes and promote the healing of urothelial damage 24 – 26 . Tyagi et al .…”

Urothelial Signaling

“…Urothelial cells appear to take up liposomes via an endocytotic process, providing evidence for a possible mechanism by which liposomes act as a drug delivery system (220). In addition, empty liposomes have shown promise to repair and enhance the barrier function of a dysfunctional urothelium (154,237,280,281).…”

“…However, even empty liposomes have shown promise to repair and enhance the barrier function of a dysfunctional urothelium (154,237,281). The effect of empty liposomes was assessed using a rat model for urothelial damage/injury (protamine sulfate) followed by intravesical instillation with KCl that resulted in bladder hyperactivity.…”