Precision-Targeted Nanotherapy for Ischemic Stroke and Related CNS Disorders

2020 Fiscal Year Research-status Report

• Project/Area Number: 20K16428
• Research Institution: Toyo University
• Principal Investigator: モハメッド シェイク 東洋大学, 学際・融合科学研究科, 准教授 (50708609)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Nano DDS / Ischemic Stroke / Central Nervous System / Blood Brain Barrier / Neuronal Degeneration

Outline of Annual Research Achievements

Background: In case of injuries, the brain has a very slow damage response which becomes severe with increasing age. The main reason for this is the rapid neurodegeneration that is accompanied by the trauma. Therefore assisting the brain in its repair mechanism is of high significance. Neurotrophic factors can assist in the neuroprotection and rescue of diseased neurons, however, they are highly sensitive to physiological media and cannot reach the lesion site in significant quantities.
Purpose: With these critical issues in mind, the project entitled ‘Precision-Targeted Nanotherapy for Ischemic Stroke and Related CNS Disorders’ was designed for the purpose of making neurotrophins, a clinical reality for patients with neuronal degeneration and physical trauma, particularly ischemic stroke. This is intended to be achieved by utilizing the specific peptide targeted hybrid solid lipid nanoformulations encapsulating the neurotrophic factors to trespass the blood brain barrier (BBB) and alleviate neuronal degeneration.
Progress in FY 2020-2021: The project has been affected by the COVID-19 pandemic and is slightly behind schedule. Still, the nanoformulations have been synthesized and their characterization and stability studies are ongoing. Cell cultures for the in vitro studies have been established.
Plan for FY 2020-2021: In vitro cellular studies will be initiated. In vivo safety assessment of the nanoformulations will be determined. Ischemic stroke mice models will be developed and the in vivo therapeutic efficacy evaluations will be initiated.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

Proposed plan for the AY 2020-2021 was: Procuring chemicals/consumables; nanoformulation synthesis/characterization; Analyzing in vitro efficacy of NF; Development of ischemic stroke models (mice/rat) using established protocols.

The accomplished parts of the project are: Part of the planned chemicals/consumable have been purchased. The nanoformulations have been synthesized and their characterization and stability studies are ongoing. Cell cultures for the in vitro studies have been established. Since the emergency was lifted in the Saitama region, work is progressing smoothly.

Reasons for the delay: The COVID-19 pandemic related incidents have affected the current project significantly. First of all, the University to which the researcher belongs and the research Centre where most of the FY 2020-21 part of the project was planned to be conducted, had imposed strict restriction on entrance and research activities as part of measures to prevent the spread of infection. Secondly, due to the international travel restrictions, procurement of certain chemicals/reagents which needed to be imported, were delayed and alternatives had to be found. Finally, due to the domestic travel restrictions, the researcher could not travel to the medical university where the in vivo part of the project was planned, therefore the animal experiments were not initiated.

Strategy for Future Research Activity

With slight delay in the planned schedule of FY 2020-21, additional efforts will be implemented for the FY 2021-22 part of the project.

The research planned for FY 2021-22 was: In vivo safety assessment of the nanoformulations; In vivo assessment of the treatment efficacy with different targeting schemes; Post-processing of organs after observation period; Assessing the motor abilities/survival statistics of the test subjects. (Communicating scientific articles, national/international meetings/conferences).

The proposed research plan for FY 2021-22 is: Apart from the portions listed above, parts of the previous year’s research backlog will also be covered. For instance, characterization of the nanoformulations and their in vitro and in vivo safety assessments will be performed. In vitro experiments to mimic the neural degeneration and the therapeutic efficacy of the nanoformulations will be assessed. Ischemic stroke mice models will be developed and the nanoformulation’s targeting and therapeutic efficacy will be determined.
Though this is the proposed plan, the effect of the COVID-19 pandemic cannot be predicted at this moment. Therefore, the final schedule will depend on the domestic and international trend towards the pandemic.

Causes of Carryover

As described in the ‘current status’ section, the COVID-19 pandemic related incidents have affected the current project significantly, including restricted expenditure.
Strict restrictions on entrance and research activities from the researcher’s University and the research Center, as part of measures to prevent the spread of infection resulted in the project’s delayed start. Also, due to international travel restrictions, certain chemicals/reagents, could not be purchased. Mainly, due to domestic travel restrictions, travel to the medical university where in vivo part of the project was planned, was cancelled. As a result, the animals required for the project were not procured and there was no expenditure for their maintenance and other chemicals required for the in vivo experiments.

The research plan for the upcoming year, as explained in the ‘planning for the future work’, will include the portions of the current year. Therefore, the remaining budget amount from the current year will be utilized for procuring chemicals/reagents and assay kits for the in vitro experiments and for the in vivo animal-related experiments which were initially planned for AY 2020-2021.