Urodynamic and immunohistochemical evaluation of intravesical capsaicin delivery using thermosensitive hydrogel and liposomes.
OBJECTIVE
Aqueous insolubility of the vanilloids such as capsaicin is a major disincentive in their intravesical therapy of detrusor hyperreflexia. We sought to overcome the delivery of this hydrophobic neurotoxin by entrapping it in a lipid bilayer of positively charged multilamellar lipid vesicles (liposomes) or in a hydrophobic polymer matrix of thermosensitive hydrogel.


METHODS
Liposomes, hydrogel and 30% ethanol/normal saline were prepared with or without 1 mM capsaicin (0.5 ml) and administered intravesically for 30 minutes to 7 groups of age matched, normal female adult Sprague-Dawley rats under halothane anesthesia. At 48 hours after intravesical instillation cystometric studies were performed using urethane anesthesia (0.04 ml per minute). The animals were subsequently sacrificed and whole bladders were harvested for histology and immunohistochemistry.


RESULTS
In normal urethane anaesthetized rats capsaicin in 30% ethanol and liposomes completely blocked micturition reflexes. Capsaicin in hydrogel did not completely block the micturition reflex but it significantly decreased bladder contraction frequency compared with vehicle controls. The results of cystometry with capsaicin in liposomes and capsaicin in 30% ethanol correlated with a significant decrease in calcitonin gene-related peptide staining of afferent nerves in the bladder wall. Photographs taken after hematoxylin and eosin staining of the bladder treated with liposomes and hydrogel in the absence of capsaicin did not reveal any adverse histological changes. There were significant histological changes in bladders treated with 30% ethanol alone.


CONCLUSIONS
In comparison with 30% ethanol liposomes are a superior vehicle for the intravesical administration of capsaicin, producing comparable efficacy with less tissue damage. Hydrogel can also serve as safe alternative option for capsaicin delivery.
Tyagi
Pradeep
P
Center of Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pennsylvania 15213, USA.
Chancellor
Michael B
MB
Li
Zhenhua
Z
De Groat
William C
WC
Yoshimura
Naoki
N
Fraser
Matthew O
MO
Huang
Leaf
L
D000283:Administration, Intravesical; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007150:Immunohistochemistry; D008081:Liposomes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D014563:Urodynamics
D008081:Liposomes; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D002211:Capsaicin