Toxicology study for magnetic injection of prednisolone into the rat cochlea
| Autor: | Mohammed Ibrahim Shukoor, Benjamin Shapiro, Bharath Ramaswamy, Mika Shimoji, Prateek Benhal, Pulkit Malik, Sandip D. Kulkarni, Jean-François Lafond, B. McCaffrey, Didier A. Depireux, Aleksandar Nelson Nacev, Andrew Broda, Irving N. Weinberg |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Hearing loss Prednisolone Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Article Injections 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Ototoxicity otorhinolaryngologic diseases medicine Animals Humans Rats Long-Evans Magnetite Nanoparticles Cochlea Inflammation Behavior Animal business.industry 021001 nanoscience & nanotechnology medicine.disease Drug Liberation Prednisolone Sodium Phosphate medicine.anatomical_structure Ear Inner Anesthesia Drug delivery Middle ear Histopathology sense organs medicine.symptom 0210 nano-technology business medicine.drug |
| Zdroj: | European Journal of Pharmaceutical Sciences. 126:33-48 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2018.06.011 |
| Popis: | This paper investigates the safety of a novel ‘magnetic injection’ method of delivering therapy to the cochlea, in a rodent model. In this method of administration, a magnetic field is employed to actively transport drug-eluting superparamagnetic iron-oxide core nanoparticles into the cochlea, where they then release their drug payload (we delivered the steroid prednisolone). Our study design and selection of control groups was based on published regulatory guidance for safety studies that involve local drug delivery. We tested for both single and multiple delivery doses to the cochlea, and found that magnetic delivery did not harm hearing. There was no statistical difference in hearing between magnetically treated ears versus ears that received intra-tympanic steroid (a mimic of a standard-of-care for sudden sensorineural hearing loss), both 2 and 30 days after treatment. Since our treatment is local to the ear, the levels of steroid and iron circulating systemically after our treatment were low, below mass-spectrometry detection limits for the steroid and no different from normal for iron. No adverse findings were observed in ear tissue histopathology or in animal gross behavior. At 2 and 30 days after treatment, inflammatory changes examined in the ear were limited to the middle ear, were very mild in severity, and by day 90 there was ongoing and almost complete reversibility of these changes. There were no ear tissue scarring or hemorrhage trends associated with magnetic delivery. In summary, after conducting a pre-clinical safety study, no adverse safety issues were observed. |
| Databáze: | OpenAIRE |
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