Sustained release of triamcinolone acetonide from an intratympanically applied hydrogel designed for the delivery of high glucocorticoid doses.
The pharmacokinetic properties and tolerability of a triamcinolone acetonide poloxamer 407 hydrogel for intratympanic application were investigated in a guinea pig model. Evaluation of in vivo release kinetics showed very high initial perilymph drug levels, with clinically relevant levels present for a minimum of 10 days. Assessment of auditory brainstem response thresholds showed a minimal, delayed and transient threshold shift, which was apparent on day 3 and resolved by day 10. No relevant histological changes of the middle and inner ear structures were noted, and hair cell counts showed no significant differences between treated and untreated ears. Thus, the triamcinolone-acetonide-loaded poloxamer 407 hydrogel is an effective vehicle for sustained high-dose inner ear glucocorticoid delivery.
Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
Clemens
C
Honeder
Elisabeth
E
Engleder
Hanna
H
Schöpper
Franz
F
Gabor
Gottfried
G
Reznicek
Jens
J
Wagenblast
Wolfgang
W
Gstoettner
Christoph
C
Arnoldner
D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D020100:Hydrogels / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014432:Tympanic Membrane / Q000187:drug effects* / Q000378:metabolism
D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D020100:Hydrogels; D014222:Triamcinolone Acetonide