Abstract | PURPOSE: Direct instillation of drug solutions into the bladder through a urethral catheter (i.e., intravesical therapy) evades systemic adverse effects of drugs used for bladder diseases. However, conventional vehicles for these drugs fail to extend duration of drug exposure in the bladder beyond the first voiding of urine postinstillation. The current study seeks to overcome the aforementioned inherent limitation of intravesical drug administration by using thermosensitive hydrogel as a matrix for sustained intravesical drug delivery. METHODS: RESULTS: Prolonged drug exposure to the bladder afforded by hydrogel was evident from the time course of FITC elimination in the urine and by the green fluorescence of FITC seen at the bladder surface when isolated 24 h after instillation. Rats instilled with free FITC voided almost all of the fluorescence in the urine within the first 8 h, whereas rats instilled with hydrogel encapsulated FITC showed sustained release up to 24 h after instillation. Using a cyclophosphamide-induced cystitis model, rats instilled with misoprostol, a synthetic PGE1 analog, showed significantly reduced frequency of urine voiding (p < 0.05) as compared to the rats instilled with saline. Histological examination of the urothelium showed near normal morphology in rats instilled with misoprostol in hydrogel, whereas extensive tissue damage was observed in rats instilled with saline. CONCLUSION:
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Authors | Pradeep Tyagi, Zhenhua Li, Michael Chancellor, William C De Groat, Naoki Yoshimura, Leaf Huang |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 21
Issue 5
Pg. 832-7
(May 2004)
ISSN: 0724-8741 [Print] United States |
PMID | 15180342
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Delayed-Action Preparations
- Fluorescent Dyes
- Hydrogels
- Protein Synthesis Inhibitors
- Misoprostol
- Cyclophosphamide
- Fluorescein-5-isothiocyanate
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Topics |
- Animals
- Cyclophosphamide
- Cystitis
(chemically induced, drug therapy, pathology)
- Delayed-Action Preparations
- Drug Delivery Systems
- Female
- Fluorescein-5-isothiocyanate
- Fluorescent Dyes
- Half-Life
- Hydrogels
- Injections
- Misoprostol
(administration & dosage, pharmacokinetics, therapeutic use)
- Protein Synthesis Inhibitors
- Rats
- Rats, Sprague-Dawley
- Stereoisomerism
- Temperature
- Urinary Bladder
(pathology)
- Urinary Incontinence
(chemically induced, drug therapy, pathology)
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