Implantable Drug Reservoir Devices for Inner Ear Delivery of Pharmacotherapeutics
OBJECTIVE: Cisplatin is a platinum-based chemotherapeutic drug that secondarily induces toxicity in inner ear sensory epithelia, contributing to auditory and vestibular dysfunction. We describe the creation of a drug reservoir device (DRD) to combat this ototoxicity for the duration of chemotherapy. As ototoxic side effects of chemotherapy may limit an oncologist's ability to prescribe first-line agents such as cisplatin, mitigating such devastating effects through prolonged topical therapy would be tremendously valuable.
STUDY DESIGN: We investigated (1) the ability of an electrospun polylactic acid DRD to provide prolonged delivery of the posited otoprotectant metformin and (2) the development of an in vitro model utilizing Sh-Sy5y human neuroblastoma cells to assess the efficacy of metformin in reducing cisplatin-induced toxicity.
SETTING: Neurophysiology laboratory.
METHODS: Basic science experiments were performed to assess DRD properties and metformin's effects on cisplatin toxicity in culture.
RESULTS: We found that DRDs with increasing polylactic acid concentrations exhibited metformin release for up to 8 weeks. In modeling elution across the round window in vitro, continued elution of metformin was observed for at least 6 weeks, as quantified by spectrophotometry. Unfortunately, metformin did not exhibit protective efficacy in this model using Sh-Sy5y cells.
CONCLUSION: While metformin was not found to be protective in Sh-Sy5y cells, these results suggest that an electrospun DRD can provide a tailorable drug delivery system providing medication for the duration of chemotherapy treatment. This represents a novel drug delivery system and efficacy screening assay with broad clinical applications in personalized delivery of inner ear therapies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:163 |
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| Enthalten in: |
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery - 163(2020), 4 vom: 19. Okt., Seite 791-798 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kita, Ashley [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.12.2020 Date Revised 14.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/0194599820930229 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310646804 |
|---|
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| 245 | 1 | 0 | |a Implantable Drug Reservoir Devices for Inner Ear Delivery of Pharmacotherapeutics |
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| 500 | |a Date Completed 10.12.2020 | ||
| 500 | |a Date Revised 14.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: Cisplatin is a platinum-based chemotherapeutic drug that secondarily induces toxicity in inner ear sensory epithelia, contributing to auditory and vestibular dysfunction. We describe the creation of a drug reservoir device (DRD) to combat this ototoxicity for the duration of chemotherapy. As ototoxic side effects of chemotherapy may limit an oncologist's ability to prescribe first-line agents such as cisplatin, mitigating such devastating effects through prolonged topical therapy would be tremendously valuable | ||
| 520 | |a STUDY DESIGN: We investigated (1) the ability of an electrospun polylactic acid DRD to provide prolonged delivery of the posited otoprotectant metformin and (2) the development of an in vitro model utilizing Sh-Sy5y human neuroblastoma cells to assess the efficacy of metformin in reducing cisplatin-induced toxicity | ||
| 520 | |a SETTING: Neurophysiology laboratory | ||
| 520 | |a METHODS: Basic science experiments were performed to assess DRD properties and metformin's effects on cisplatin toxicity in culture | ||
| 520 | |a RESULTS: We found that DRDs with increasing polylactic acid concentrations exhibited metformin release for up to 8 weeks. In modeling elution across the round window in vitro, continued elution of metformin was observed for at least 6 weeks, as quantified by spectrophotometry. Unfortunately, metformin did not exhibit protective efficacy in this model using Sh-Sy5y cells | ||
| 520 | |a CONCLUSION: While metformin was not found to be protective in Sh-Sy5y cells, these results suggest that an electrospun DRD can provide a tailorable drug delivery system providing medication for the duration of chemotherapy treatment. This represents a novel drug delivery system and efficacy screening assay with broad clinical applications in personalized delivery of inner ear therapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cisplatin | |
| 650 | 4 | |a drug delivery | |
| 650 | 4 | |a electrospinning | |
| 650 | 4 | |a inner ear | |
| 650 | 4 | |a metformin | |
| 650 | 4 | |a ototoxicity | |
| 650 | 4 | |a round window | |
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| 650 | 7 | |a Cisplatin |2 NLM | |
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| 700 | 1 | |a Saldate, Johnny |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Courtney |e verfasserin |4 aut | |
| 700 | 1 | |a Chellappa, Nitika |e verfasserin |4 aut | |
| 700 | 1 | |a Jong, Jeremy |e verfasserin |4 aut | |
| 700 | 1 | |a Matsuda, Riley |e verfasserin |4 aut | |
| 700 | 1 | |a Schmidt, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Shih, Brandon |e verfasserin |4 aut | |
| 700 | 1 | |a Shafqat, Iram |e verfasserin |4 aut | |
| 700 | 1 | |a Schoettler, Kari |e verfasserin |4 aut | |
| 700 | 1 | |a Acharya, Shiv |e verfasserin |4 aut | |
| 700 | 1 | |a Seidlits, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Hoffman, Larry |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery |d 1982 |g 163(2020), 4 vom: 19. Okt., Seite 791-798 |w (DE-627)NLM012595721 |x 1097-6817 |7 nnns |
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