Prevention of peritoneal adhesions in the rat with sustained intraperitoneal dexamethasone delivered by a novel therapeutic system.
The rat caecal crush model for the production of intraperitoneal adhesions was optimized with respect to an objective adhesion grading system based on the determination of the incidence of adhesions and the caecal adherent surface area. Intraperitoneal saline solution given before closure of the peritoneum significantly reduced the severity but not the incidence of adhesions. The addition of dexamethasone crystal suspension led to somewhat lower incidence of adhesions but the mean adherent surface area values were not different from the saline regimen. However, sustained release of dexamethasone by use of intraperitoneal biodegradable poly(lactide-co-glycolide) microparticles as a novel therapeutic system further reduced both the incidence and the severity of adhesions. Despite of the differences in therapeutic effects glucocorticoid-associated local and systemic adverse effects were similar in both regimens. As effective adhesion prophylaxis with glucocorticoids appears to be a balance between benefit and adverse reactions, optimal drug delivery is mandatory. The novel biodegradable therapeutic system is superior to the intraperitoneal crystal suspension regimen in the rat and should be tested further in clinical trials.
Höckel
M
M
Department of Obstetrics and Gynaecology, University Hospital, Mainz, West Germany.
Ott
S
S
Siemann
U
U
Kissel
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005260:Female; D010529:Peritoneal Cavity; D010532:Peritoneal Diseases / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control
D003692:Delayed-Action Preparations; D003907:Dexamethasone