Intravesical liposome administration—a novel treatment for hyperactive bladder in the rat

Fraser, Matthew O.; Chuang, Yao‐Chi; Tyagi, Pradeep; Yokoyama, Teruhiko; Yoshimura, Naoki; Huang, Leaf; Groat, William C. de; Chancellor, Michael B.

doi:10.1016/s0090-4295(02)02281-1

Cited by 83 publications

(60 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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. Treatment with empty liposomes was found to partially reverse the irritation-induced increase in bladder contractions (104). These findings provide evidence that liposomes may restore the damaged or disrupted urothelial layer that may occur following infection or inflammation.…”

Section: B Liposomesmentioning

confidence: 57%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

390

362

View full text Add to dashboard Cite

The urothelium, which lines the inner surface of the renal pelvis, the ureters, and the urinary bladder, not only forms a high-resistance barrier to ion, solute and water flux, and pathogens, but also functions as an integral part of a sensory web which receives, amplifies, and transmits information about its external milieu. Urothelial cells have the ability to sense changes in their extracellular environment, and respond to chemical, mechanical and thermal stimuli by releasing various factors such as ATP, nitric oxide, and acetylcholine. They express a variety of receptors and ion channels, including P2X3 purinergic receptors, nicotinic and muscarinic receptors, and TRP channels, which all have been implicated in urothelial-neuronal interactions, and involved in signals that via components in the underlying lamina propria, such as interstitial cells, can be amplified and conveyed to nerves, detrusor muscle cells, and ultimately the central nervous system. The specialized anatomy of the urothelium and underlying structures, and the possible communication mechanisms from urothelial cells to various cell types within the bladder wall are described. Changes in the urothelium/ lamina propria ("mucosa") produced by different bladder disorders are discussed, as well as the mucosa as a target for therapeutic interventions.

show abstract

Section: B Liposomesmentioning

confidence: 57%

Urothelial Signaling

Birder

Andersson

2013

Physiological Reviews

390

362

View full text Add to dashboard Cite

show abstract

“…A solution of protamine sulfate (Sigma, St. Louis, MO; 10 mg/ml in sterile saline) was then infused into the bladder (Յ1 ml) and maintained (45 min) in the bladder while the rat was anesthetized with isoflurane (1-2%) to prevent voiding and expulsion of bladder contents (15). Protamine sulfate is used to disrupt urothelial cell-to-cell contact and increase urothelial permeability (11,25). This concentration of protamine sulfate does not affect voiding frequency (11,25).…”

Section: Drug Treatmentsmentioning

confidence: 99%

“…Protamine sulfate is used to disrupt urothelial cell-to-cell contact and increase urothelial permeability (11,25). This concentration of protamine sulfate does not affect voiding frequency (11,25). The bladder was then flushed with 0.9% sterile saline and emptied.…”

Section: Drug Treatmentsmentioning

confidence: 99%

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

Klinger

Vizzard²

2008

American Journal of Physiology-Renal Physiology

106

View full text Add to dashboard Cite

NTR in bladder function in control and CYP-treated rats was determined using conscious cystometry and immunoneutralization or PD90780, a compound known to specifically block NGF binding to p75NTR . An anti-p75 NTR monoclonal antibody or PD90780 was infused intravesically and cystometric parameters were evaluated. Both methods of p75 NTR blockade significantly (P Յ 0.05) decreased the intercontraction interval and void volume in control and CYP-treated rats. Intravesical infusion of PD90780 also significantly (P Յ 0.001) increased intravesical pressure and increased the number of nonvoiding contractions during the filling phase. Control intravesical infusions of isotype-matched IgG and vehicle were without effect. Intravesical instillation of PD90780 significantly (P Յ 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75 NTR expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75 NTR blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75 NTR and NGF-TrkA signaling. NTR belongs to the tumor necrosis factor-␣ family of receptors (1, 4, 8). p75 NTR binds all neurotrophins, including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4/5. NGF-TrkA signaling is involved in some inflammatory effects of NGF (50), including sensitization of nociceptive afferents and the release of neuropeptides. TrkA expression is increased in bladder afferent cells in lumbosacral dorsal root ganglia (DRG) with acute and chronic cyclophosphamide (CYP)-induced bladder inflammation (51). In addition, p75 NTR expression is also significantly upregulated in bladder afferent cells (2.4-to 2.8-fold) in lumbosacral DRG after CYP-induced cystitis (39).The pan-neurotrophin receptor p75 NTR exhibits a ubiquitous distribution and has many functions and multiple binding partners and ligands (4,8). In the absence of Trk expression, p75NTR is suggested to be involved in apoptosis and regulation of neuronal growth (4, 27); however, in the presence of TrkA, p75 NTR is suggested to function by enhancing Trk binding to neurotrophins (3,4,70). p75 NTR expression has previously been identified in the urinary bladder (61,66,67) but few studies have examined the role of p75 NTR in bladder function or in the context of urinary bladder inflammation (66). Although we do know that p75NTR expression is present in micturition reflex pathways in control rats and is regulated with CYP-induced cystitis (39), the potential role(s) of p75 NTR in urinary bladder reflexes have not been explored. In this study, we determined 1) expression of p75 NTR in the urinary bladder with immunohistochemistry and Western blot and regulation of p75 NTR expression after CYP-induced cystitis, 2) the effect of immunoneutralization with an anti-p75 NTR monoc...

show abstract

“…Previously, liposomes were shown to improve the aqueous solubility of hydrophobic drugs such as paclitaxel (Taxol) and amphotericin; a recent report by the laboratory of one of the authors in the United States discussed the use of liposomes as vehicles for capsaicin and evaluated their potential as a vehicle for intravesical delivery in rats [71]. Liposomes were able to deliver capsaicin with efficacy similar to that of ethanolic saline, but toxicity to the bladder was drastically reduced [72]. Liposomes are versatile drug delivery vehicles due to the flexibility of their compositions.…”

Section: Liposomesmentioning

confidence: 99%

New Frontiers in Intravesical Therapies and Drug Delivery

et al. 2006

View full text Add to dashboard Cite

e u r o p e a n u r o l o g y 5 0 ( 2 0 0 6 ) 1 1 8 3 -1 1 9 3 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Article info AbstractObjectives: The intravesical route permits site-specific delivery of drugs with a reduced side-effect profile as compared to oral delivery systems, either by avoiding first-pass metabolism or by obtaining a local effect. We investigated mechanisms related to urothelium permeability and new physical and chemical developments in intravesical drug delivery that potentially permit successful treatment of several bladder dysfunction. Methods: A literature review. Results: Pharmacologic agents increasing urothelial permeability and useful for clinical purposes have been described, such as dimethylsulfoxide, protamine sulphate, chitosan, and nystatin. Among physical approaches, electromotive drug administration appears to be more effective than intravesical passive diffusion in delivering drugs through the urothelium into deeper layers of the bladder. Experimental and clinical reports demonstrated that electric current significantly increases the transport of local anaesthetics, mytomicin C, oxybutynin, resiniferatoxin, epinephrine, and dexamethasone. Among new chemical approaches, cell-penetrating peptides posses the ability to translocate macromolecular drugs across membranes of urothelial cells. The therapeutic benefits of sustained delivery afforded by thermosensitive hydrogel, which forms a depot for hydrophilic and hydrophobic drugs, have been demonstrated by delivering anti-inflammatory drugs. Liposomes improve the aqueous solubility of several hydrophobic drugs such as taxol, amphotericin, and capsaicin. Conclusions: Electromotive drug administration, new in situ delivery systems, and bioadhesive liposomes may make it possible to extend intravesical therapy and drug administration to many bladder diseases. Research to expand knowledge of the chemical and physical properties of the bladder and processes regulating drug transport across biologic membranes is needed to make this a reality.

show abstract

Intravesical liposome administration—a novel treatment for hyperactive bladder in the rat

Cited by 83 publications

References 22 publications

Urothelial Signaling

Urothelial Signaling

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

New Frontiers in Intravesical Therapies and Drug Delivery

Contact Info

Product

Resources

About

Intravesical liposome administration—a novel treatment for hyperactive bladder in the rat

Cited by 83 publications

References 22 publications

Urothelial Signaling

Urothelial Signaling

Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis

New Frontiers in Intravesical Therapies and Drug Delivery

Contact Info

Product

Resources

About

Role of p75^NTR in female rat urinary bladder with cyclophosphamide-induced cystitis