Tıp Fakültesi / Faculty of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/11727/1403

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Author: search.filters.author.Canpinar, Handesearch.filters.applied.f.rights: search.filters.rights.info:eu-repo/semantics/openAccess

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    A New Nanosuspension Prepared With Wet Milling Method For Oral Delivery Of Highly Variable Drug Cyclosporine A: Development, Optimization And In Vivo Evaluation
    (2022) Pinar, Sila Gulbag; Canpinar, Hande; Tan, Cagman; Celebi, Nevin; 35017012
    Cyclosporine A (CsA) is a cyclic polypeptide, that has been widely used for immunosuppression. This study aims to develop nanosuspension for oral administration of CsA using the wet milling (WM) method one of the top down technologies. The WM method was optimized by studying the effects of critical process parameters for WM on the particle size (PS), particle size distribution (PDI), and zeta potential (ZP) of nanosuspensions using the Design of Experiment (DoE) approach. Nanosuspension was developed using hydroxypropyl methylcellulose (HPMC) and sodium dodecyl sulfate (SDS) and in vitro characterization studies were performed. In vitro dissolution and in vivo pharmacokinetic studies were conducted with biorelevant media (fasted and fed state simulated fluids) and fasted and fed states in rats, respectively. In vivo immunological studies were also performed. PS, PDI, and ZP values for nanosuspension were approximately 600 nm, 0.4,-25 mV, respectively. The solubility of CsA was increased by 4.5-folds by nanosuspensions. Dissolution studies showed that nanosuspension had higher dissolution than the commercial product in the FeSSIF medium. The pharmacokinetic study indicated that AUC0(-24) values of CsA nanosuspension were to be 2.09 and 5.51-fold higher than coarse powder in fasted and fed conditions, respectively. Immunological studies were carried out after oral administration of nano suspension for 21 days, the ratio of CD4+/CD8+ was found to be more acceptable than the commercial product. These results demonstrated that nanosuspension is a promising approach for increasing the bioavailability and avoiding the food effect on absorption of CsA which one of the highly variable drugs.
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    Investigation of the Possible Protective Effects of Ketamine and Dantrolene on the Hippocampal Apoptosis and Spatial Learning in Rats Exposed to Repeated Electroconvulsive Seizures as a Model of Status Epilepticus
    (2020) Gursoy, Ibrahim Devrim; Barun, Sureyya; Erdem, Remzi; Keskin, Ulya; Kiziltas, Murat; Atilla, Pergin; Muftuoglu, Sevda; Yuce, Deniz; Narin, Firat; Ertunc, Mert; Sara, Yildirim; Canpinar, Hande; 0000-0002-7537-2170; 32705669
    AIM: To evaluate the possible neuroprotective effects of ketamine and dantrolene on the hippocampal apoptosis and spatial learning in rats exposed to repeated electroconvulsive seizures (ECS) as a model of status epilepticus (SE). MATERIAL and METHODS: Twenty-four rats were assigned to 4 groups. 1st Group was Sham. 2nd Group was ECS: ECS was induced by ear electrodes via electrical stimulation. The same ECS protocol was applied to the 3th and 4th Groups which received ketamine (40 mg/kg s.c.) or dantrolene (5 mg/kg i.p.) 1 h before each ECS, respectively. Following 30 days of recovery, the cognitive status of the animals was evaluated via Morris Water Maze (MWM). The same experimental protocol was repeated 14 days afterward to evaluate the retention of the memory. Hippocampal apoptosis was examined in corresponding experimental groups. RESULTS: All the animals in four groups learned the task with no significant difference between groups in MWM. The ECS+ketamine group showed memory impairment 14 days afterward. ECS+dantrolene group was not different from controls. ECS caused long term apoptotic processes in dentate gyrus (DG) and non-apoptotic neuronal injury in CA1 and CA2. CONCLUSION: Dantrolene and ketamine inhibited apoptosis and showed neuroprotective effects. Although ketamine and dantrolene inhibited ECS-induced apoptosis and non-apoptotic injury, they did not produce similar effects on memory retention. It will be warranted to evaluate cognitive dysfunction by taking into consideration the other factors in addition to apoptosis and neurodegenerative changes.