Influence of the glycosaminoglycan layer on the permeation of hypericin in rat bladders in vivo.
OBJECTIVE
To investigate the influence of a glycosaminoglycan (GAG) layer on the specific location of hypericin in superficial urothelial carcinoma lesions of the bladder after intravesical instillation.


METHODS
Fisher rat bladders were incubated with 15 or 30 microm hypericin for 2 h. To examine the influence of the GAG layer on the permeation of hypericin, bladders were pre-treated with chondroitinase ABC, n-dodecyl-beta-d-maltoside (DDM) or sodium dodecyl sulphate (SDS) to disrupt, or protamine to neutralise the GAG layer before incubating with hypericin. After incubation, the photosensitizer permeation was examined quantitatively in cryostat sections of the bladders, using fluorescence microscopy and image analysis.


RESULTS
Disrupting or neutralising the GAG layer in the bladder had no influence on the permeation of hypericin. Pre-treatment of the bladder with chondroitinase, DDM or SDS resulted in a significantly lower accumulation of hypericin, whereas neutralising the GAG layer in rats with protamine had no significant effect on the biodistribution of hypericin.


CONCLUSIONS
The GAG matrix causes no obstacle to the permeation of hypericin in the urothelium of the bladder, and modification of this GAG layer cannot explain the enhanced accumulation of hypericin in superficial bladder tumours.
Huygens
Ann
A
Laboratorium voor Farmaceutische Biologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium.
Crnolatac
Ivo
I
Maes
Jan
J
Van Cleynenbreugel
Ben
B
Van Poppel
Hendrik
H
Roskams
Tania
T
de Witte
Peter A M
PA
D000704:Analysis of Variance; D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D017319:Photosensitizing Agents / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D001743:Urinary Bladder / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
D000873:Anthracenes; D000970:Antineoplastic Agents; D006025:Glycosaminoglycans; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin