Precision-Targeted Nanotherapy for Ischemic Stroke and Related CNS Disorders

2021 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, バイオ・ナノエレクトロニクス研究センター, 研究助手 (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

The project entitled ‘Precision-Targeted Nanotherapy for Ischemic Stroke and Related CNS Disorders’ is designed to make neurotrophins, a clinical reality for patients with neuronal degeneration and physical trauma, particularly ischemic stroke. For this purpose, specific peptide targeted hybrid solid lipid nanoformulations encapsulating specific neurotrophic factors with ability to trespass the blood brain barrier (BBB) and alleviate neuronal degeneration are being utilized with promising preliminary results.
Progress in FY 2021-2022: As a continuation of the previous year (2020-2021), the project has been affected by the COVID-19 pandemic. Though slightly behind schedule, major progress has been made in the experimental schedule. The nanoformulations, which had been thoroughly characterized for their physicochemical properties, have shown excellent compatibility to cells in vitro. Promising results have been attained in the invitro studies and the project has moved to in vivo investigations. Ischemic stroke models have been established using male SPF mice (C57BL/6J). Biocompatibility of the nanoformulations have been tested and the therapeutic evaluations have been initiated.
Plan for FY 2022-2023: Continuation of in vivo therapeutic efficacy evaluations of the nanoformulations.

Current Status of Research Progress

3: Progress in research has been slightly delayed.

Reason

The research planned for FY 2021-22 was:
In vivo safety assessment of the NF; 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).
Current Status (Objectives accomplished):
In vitro studies with the nanoformulations have been completed. Ischemic stroke models have been established using male SPF mice (C57BL/6J). Compatibility of the nanoformulations have been tested and the therapeutic evaluations have been initiated.
Reasons for the delay:
There has been a slight delay in the project execution due to COVID-19 pandemic related incidents. Due to the domestic travel restrictions (institutional and prefectural), the researcher could not travel to the medical university where the in vivo part of the project was planned, therefore the animal experiments could not be initiated as planned and had a delayed start.

Strategy for Future Research Activity

With slight delay in the planned schedule of FY 2021-22, additional efforts will be implemented for the FY 2022-23 part of the project.
The research planned for FY 2022-23 was:
Continuation of investigations; Based on the observations/results, further investigation of the NF against other neurodegenerative disorders would be initiated. Prospects of acquiring patent would be explored. (Communicating scientific articles).
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, continuation of in vivo therapeutic efficacy evaluations of the nanoformulations and publication of scientific manuscripts.
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.
Restrictions on entrance and research activities from the researcher’s University, 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 delayed. As a result, the in vivo experiments were delayed and the expenditure related to animal experiments was reduced as was for other chemicals required for the in vivo experiments. Also, due to international travel restrictions, attendance to international conferences was cancelled, thus postponing the registration and travel related expenses.
The research plan for the upcoming year, will include the portions of the current year. Therefore, the remaining budget amount from the current year will be properly utilized for procuring chemicals/reagents and mice for the in vivo animal-related experiments.