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.
Conclusion-The intraoperative application of glucocorticoid-loaded hydrogels seems to cause a reduction in neutrophil infiltration. No beneficial effect on hearing thresholds was detected.Objectives-To evaluate the application of dexamethasone-and triamcinolone-acetonide-loaded hydrogels for effects on hearing-preservation and foreign-body reaction in a guinea pig model for cochlear implantation.Methods-48 guinea pigs (n= 12/group) were implanted with a single channel electrode and intraoperatively treated with 50 µl of a 20% w/v poloxamer 407 hydrogel loaded with 6% dexamethasone or 30% triamcinolone-acetonide, a control hydrogel, or physiological saline. Click-and tone burst-evoked compound action potential thresholds were determined pre-and directly postoperatively as well as on days 3, 7, 14, 21 and 28. At the end of the experiment, temporal bones prepared for histological evaluation by a grinding/polishing technique with the Results-The intratympanic application of glucocorticoid-loaded hydrogels did not improve the preservation of residual hearing in this cochlear implant model. The foreign body reaction to the electrode appeared reduced in the glucocorticoid treated animals. No correlation was found between the histologically described trauma to the inner ear and the resulting hearing thresholdshifts.
Objectives/Hypothesis: To evaluate the selective glucocorticoid receptor agonist (SEGRA) compound A, a potential novel therapeutic for inner ear disorders, for ototoxic effects.Study Design: Laboratory animal study. Methods: Experimental guinea pigs were grouped as follows: Systemic application of compound A (1.5 mg/kg and 4.5 mg/kg; n 5 6/group) and intratympanic application of compound A (1 mM and 10 mM; n 5 6/group). Contralateral ears in topically treated animals served as controls. Hearing thresholds were determined by auditory brainstem response before and directly after the application of compound A, as well as on days 3, 7, 14, 21, and 28. At the end of the experiments, temporal bones were harvested for histological evaluation.Results: Systemic administration of compound A (1.5 mg/kg and 4.5 mg/kg) did not cause hearing threshold shifts, whereas the intratympanic injection (1 mM and 10 mM) resulted in a hearing loss. Histological analysis of the middle and inner ears after topical compound A application showed alterations in the tympanic membranes, the auditory ossicles, and the round window membranes, whereas spiral ganglion cells and hair cells were not affected.Conclusion: SEGRAs such as compound A could provide novel therapeutic options for the treatment of inner ear disorders and reduce metabolic side effects. Whereas the intratympanic application of compound A resulted in a hearing loss, the systemic application of compound A merits evaluation for otoprotective effects in trauma models.
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