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| Name : |
Yalda |
| Surname : |
Hosseinzadeh Ardakani |
| From : |
Tuesday, April 4, 2023 |
| To : |
Saturday, October 7, 2023 |
| Position : |
Associate professor |
| School/Research center : |
School of Pharmacy |
| |
|
| subject : |
Polymer mediated, from a straight cochlear electrode to sustained release drug delivery |
| Venue : |
Macquarie University |
| Sabbatical Leave Period : |
6 months |
| Country : |
Australia |
| |
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| 1.Brief summary of Leave : |
As mentioned in the proposal, the main objective of this study was the use of straight cochlear implant electrodes using thermoresponsive drug loaded polymer inorder to place into the inner ear for treatment of Menier's syndrom. Although the main goal of this proposal was developing a linear implant as drug delivery system, but after starting the project, the research team decided to focus on the amount of drug to be loaded in the drug delivery system which would be able to produce the required drug levels in the epilanph. In order to determine the amount of drug required to be released in the cochlear assosiated fluids, it is necessary to evaluate the drug concentration in these fluids under therapeutic conditions. As a few studies were found in literature review, and duo to my experiences in pharmakokinetics, the primary objective of the study was changed to determine the drug leveles in the cohlear fluids following administration of different drug doses after intramascular adminisrtation in an animal model. For this purpose and in order to obtain a suitable animal model to simultaneuse determination of drug concentrations in plasma and cochlear fluids at therapeutic levels, rat and guinea pig animal models were investigated, and after several surgeries, the guinea pig animal model was selected due to better access to the cochlear. In the next step, the suggested therapeutic dexamethasone doses in the guinea pig animal model for the treatment of Meniere's syndrome were selected and both plasma and cochlear samles were collected and stored at -80 ˚C in different time intervals until further analysis. The dexamethasone will be quantified in both plasma and cochlear using the high-performance liquid chromatography/tandem mass spectrometry method, which was previously fully validated. The concentrations and the corresponding pharmacokinetic parameters will be estimated using noncompartmental methods to estimate the amount of drug that should be loaded in delivery system. |
| 2.List the objectives of your sabbatical leave as listed in your proposal and indicate how completely they were met : |
In the proposal, the main objective of this study was the use of straight cochlear implant electrodes using thermoresponsive drug loaded polymer inorder to place into the inner ear for treatment of Menier's syndrom. After starting the project, the research team decided to focus on the amount of drug to be loaded in the drug delivery system which would be able to produce the required drug levels in the epilanph. Therefore, the objectives changed as follows: • Suitable animal model selection • Set up the animal surgery method to separate cochlear • Plasma and cochlear sample collections after drud administration • Validating a sutible analytical method to determine drug concentration in biofluids • Pharmacokinetic data analysis to obtain the amount of drug to be loaded |
| 3.Acheivements(Publications,research,et.al.) : |
The result of this ُsabatical leave will be a review article (from the primary research steps) and a research article, which will be finalized and ready for submission in the next few weeks. |
| 4.Assessment of Value of Sabbatical leave(benefits,faculty development,future professional activities,...) : |
Menier's syndrom is characterized by potentially severe and debilitating episodes of vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. The hearing loss and ringing in the ears can become constant over time. It most often starts in people 40 to 60 years old. Females are more commonly affected than males. Althogh the cause of this disease is unclear, both genetic and environmental factors are likely to be envolved. Unfortunately, no definite cure is known and the administered medication just help during the attacks to treat the nausea and anxietyA low-salt diet, diuretics, and corticosteroids may be tried. Injections into the ear or surgery may also be tried if other measures are not effective, but are associated with risks. Therefore cochlear implantation could be one of the gold standard for patients with severe sensorineural hearing loss and continues to be a strong focus of cochlear implants innovation, and a wide range of electrode designs have been considered. The available data show that straight and flexible electrodes meet the criteria for optimal configuration. Nowadays, several researches have focused on developing drug delivery systems for transplanted cochlea to maximize hearing retention. In general, there are three ways to introduce a drug into the cochlea: systemic drug administration, intratympanic, and intracochlear delivery systems. As this syndrome has a course of 5–15 years, a wide range of side effects are probable along with systemic drug delivery in patients. On the other hand, although the intratympanic injection of liquid drugs are the most widely used of all the current inner ear treatments, the investigated data in three systematic reviews were found to be insufficient to decide if this therapy has positive effects. According to the advantages of straight electrodes bringing to both physisions and patients, a drug-loaded straight electrode using thermoresponsive polymers for inner ear for treatments was stablished. In order to determine the amount of drug required to be released in the cochlear assosiated fluids, it is necessary to evaluate the drug concentration in these fluids under therapeutic conditions. As a few studies were found in literature review, the primary objective of the study was changed to determine the drug leveles in the cohlear fluids following administration of different drug doses after intramascular adminisrtation in an animal model. It should be noted that creating a suitable animal model and the assosiated surgical technique to access the cochlea was a unique experience during this sabatical leave. Also, due to the importance of establishing scientific communication between universities and in order to conduct further research on Ménière's patients, several brainstorming sessions were held with experts from Tehran University of Medical Sciences with the special cooperation of the Vice Dean for International Affairs of the Faculty of Pharmacy. |
| Additional material may be attached in response to the above summary : |
https://gsia.tums.ac.ir/images/UserFiles/78816/Forms/280/Invitation letter-Dr Ardakani(2)_1.pdf |
| Department Head/Research Center Chair : |
Dr Mohsen Asadnia |
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