In vivo accumulation of different hypericin ion pairs in the urothelium of the rat bladder.
OBJECTIVE
To optimise the diagnostic and phototherapeutic efficacy of hypericin in superficial bladder cancer, by developing a bladder instillation fluid that does not depend on the presence of plasma proteins for an appropriate and reliable urothelial uptake of hypericin.


METHODS
Sodium hypericinate (in distilled water, in sodium phosphate buffer, or in polyethylene glycol) and several other hypericinate salts (potassium, lysine, TRIS or hexylamine) were instilled with no plasma constituents into the rat bladder. The accumulation of hypericin was assessed with fluorescence microscopy.


RESULTS
The diagnostic and phototherapeutic efficacy of hypericin depends on its ability to penetrate the tumour lesions sufficiently to show a fluorescent signal or elicit a photodynamic response. Several instillation fluids meet the purpose, as the urothelial accumulation of hypericin was similar to that obtained with the instillation fluid supplemented with plasma proteins, used in clinical practice. The highest concentrations of hypericin in the urothelium of the rat bladder were obtained with hypericin instillation solutions prepared with distilled water or 20% polyethylene glycol 400 in distilled water. Fluorescence microscopy showed that hypericin was selectively localized in the urothelium. Furthermore, all variables investigated (hydrophilic/lipophilic balance, pH, saline, presence of organic solvent) can dramatically influence the in vivo accumulation of hypericin.


CONCLUSIONS
An appropriate and reliable urothelial uptake of hypericin does not depend on the presence of plasma protein supplements in the bladder instillation fluid.
Huygens
Ann
A
Laboratory Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Science, UZ Gasthuisberg, KU Leuven, Van Evenstraat 4, B-3000 Leuven, Belgium.
Kamuhabwa
Appolinary R
AR
van Cleynenbreugel
Ben
B
van Poppel
Hendrik
H
Roskams
Tania
T
de Witte
Peter A M
PA
D000283:Administration, Intravesical; D000818:Animals; D000873:Anthracenes; D004337:Drug Carriers; D005260:Female; D007477:Ions; D008856:Microscopy, Fluorescence; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010778:Photochemotherapy / Q000379:methods; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D019459:Urothelium / Q000378:metabolism*
D000873:Anthracenes; D004337:Drug Carriers; D007477:Ions; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin