Sarpogrelate Delivered via Osmotic Pump Improves Residual Hearing Preservation After Cochlear Implantation
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Objectives. This study evaluated the effects of sarpogrelate, a selective 5-hydroxytryptamine (5-HT) 2A receptor antago- nist, on the preservation of residual hearing and modulation of inflammatory responses following cochlear implanta- tion (CI) in an animal model. Methods. The damaging effects of CI were simulated in male albino guinea pigs using a dummy electrode. Animals were al- located to three groups: control (n = 12, dummy electrode insertion only), SPG-1004 (n = 7, low-capacity pump deliv- ering sarpogrelate), and SPG-2004 (n = 6, high-capacity pump delivering sarpogrelate). Sarpogrelate was administered via osmotic pumps at two different volumes, and its effects on hearing thresholds, histological outcomes, and expres- sion of inflammation-related genes were assessed. Hearing was evaluated using auditory brainstem response (ABR) thresholds measured at baseline (preoperatively) and at 1, 7, and 30 days postoperatively. Results. Administration of sarpogrelate via an osmotic pump resulted in significant hearing preservation across all tested frequencies at 1 month post-surgery (P <0.05) compared with the control group, which underwent dummy electrode insertion only. Histological analysis revealed that cochlear fibrosis and inflammatory cell infiltration were markedly reduced in the sarpogrelate-treated groups, especially in the group receiving the higher pump volume. Gene expres- sion analysis supported these findings by showing a significant reduction in inflammation-related markers in the sar- pogrelate-treated groups. Conclusion. Sarpogrelate exhibited a protective effect against the loss of residual hearing after CI, likely due to its anti-in- flammatory and antifibrotic properties. In addition, the osmotic pump enabled controlled, sustained delivery of the drug over time. These findings indicate that administering sarpogrelate via an osmotic pump represents a promising pharmacological strategy for improving postoperative outcomes in CI patients by preserving residual hearing.
Abstract
Objectives. This study evaluated the effects of sarpogrelate, a selective 5-hydroxytryptamine (5-HT) 2A receptor antago- nist, on the preservation of residual hearing and modulation of inflammatory responses following cochlear implanta- tion (CI) in an animal model. Methods. The damaging effects of CI were simulated in male albino guinea pigs using a dummy electrode. Animals were al- located to three groups: control (n = 12, dummy electrode insertion only), SPG-1004 (n = 7, low-capacity pump deliv- ering sarpogrelate), and SPG-2004 (n = 6, high-capacity pump delivering sarpogrelate). Sarpogrelate was administered via osmotic pumps at two different volumes, and its effects on hearing thresholds, histological outcomes, and expres- sion of inflammation-related genes were assessed. Hearing was evaluated using auditory brainstem response (ABR) thresholds measured at baseline (preoperatively) and at 1, 7, and 30 days postoperatively. Results. Administration of sarpogrelate via an osmotic pump resulted in significant hearing preservation across all tested frequencies at 1 month post-surgery (P <0.05) compared with the control group, which underwent dummy electrode insertion only. Histological analysis revealed that cochlear fibrosis and inflammatory cell infiltration were markedly reduced in the sarpogrelate-treated groups, especially in the group receiving the higher pump volume. Gene expres- sion analysis supported these findings by showing a significant reduction in inflammation-related markers in the sar- pogrelate-treated groups. Conclusion. Sarpogrelate exhibited a protective effect against the loss of residual hearing after CI, likely due to its anti-in- flammatory and antifibrotic properties. In addition, the osmotic pump enabled controlled, sustained delivery of the drug over time. These findings indicate that administering sarpogrelate via an osmotic pump represents a promising pharmacological strategy for improving postoperative outcomes in CI patients by preserving residual hearing.