Intravesical liposome administration--a novel treatment for hyperactive bladder in the rat.
OBJECTIVE
To examine the effect of intravesical administration of liposomes (LPs) on chemically induced bladder hyperactivity in the rat. It has been suggested that interstitial cystitis (IC) is associated with a dysfunctional or leaky epithelium. Thus, enhancement of epithelial barrier function might be useful in the treatment of IC. LPs are vesicles that are concentric phospholipid bilayers separated by an aqueous compartment and can fuse with cells to provide a molecular film that can promote wound healing.


METHODS
The intravesical pressure was recorded using a transurethral catheter in adult female Sprague-Dawley rats anesthetized with urethane (1.2 g/kg subcutaneously). Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. Continuous cystometrograms were performed by slowly filling the bladder (0.04 mL/min) with solutions of varying compositions, including saline, acetic acid (AA, 0.1%), potassium chloride (KCl, 500 mM), protamine sulfate (PS, 10 mg/mL), LPs, PS/KCl, or LPs/KCl. The parameters measured included the intercontraction interval (ICI), amplitude of bladder contractions, compliance, and micturition pressure threshold.


RESULTS
The ICI was decreased after exposure to AA (79.8% decrease) or PS/KCl (81% decrease); however, the ICI was not changed after LPs, PS, or KCl alone. The decreased ICI was partially reversed after infusion of LPs (172.8% increase) or LPs/KCl (63% increase), but was not significantly changed after switching to saline or KCl administration. Pretreatment with capsaicin delayed the onset of the irritative effects of AA by approximately 30 to 60 minutes, but had not changed the magnitude after 2 hours of infusion.


CONCLUSIONS
Intravesical administration of PS/KCl or AA activates capsaicin-sensitive and capsaicin-resistant afferents in a time-dependent sequence that is partially reversed by LP infusion. We hypothesize that LPs might enhance the barrier properties of a dysfunctional uroepithelium and increase resistance to irritant penetration. Thus, intravesical LP administration could be a novel treatment of patients with IC.
Fraser
Matthew O
MO
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Chuang
Yao-Chi
YC
Tyagi
Pradeep
P
Yokoyama
Teruhiko
T
Yoshimura
Naoki
N
Huang
Leaf
L
De Groat
William C
WC
Chancellor
Michael B
MB
D000283:Administration, Intravesical; D000818:Animals; D018856:Cystitis, Interstitial / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004848:Epithelium / Q000187:drug effects; D005260:Female; D008081:Liposomes / Q000008:administration & dosage / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014555:Urination Disorders / Q000188:drug therapy; D014945:Wound Healing / Q000502:physiology
D008081:Liposomes