Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method

With ANY BRAINS at all in stroke they should be able to put two and two together matching the gene transfer with this:

Evaluation of Gene Therapy as an Intervention Strategy to Treat Brain Injury from Stroke  May 2016 

And create some useful therapies if there are two functioning neurons that can be sparked in our fucking failures of stroke associations. I don't care that this is in mice, take a chance on clinically testing these together in humans

Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method

Authors Ogawa K, Fuchigami Y, Hagimori M, Fumoto S, Miura Y, Kawakami S
Received 17 November 2017
Accepted for publication 1 February 2018
Published 16 April 2018 Volume 2018:13 Pages 2309—2320
DOI https://doi.org/10.2147/IJN.S157375
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Govarthanan Muthusamy
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Thomas J Webster

Koki Ogawa,^1,* Yuki Fuchigami,^1,* Masayori Hagimori,¹ Shintaro Fumoto,² Yusuke Miura,¹ Shigeru Kawakami<sup>1

1</sup>Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; ²Department of Pharmaceutics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan

*These authors contributed equally to this work

Introduction: We previously developed anionic ternary bubble lipopolyplexes, an ultrasound-responsive carrier, expecting safe and efficient gene transfection. However, bubble lipopolyplexes have a low capacity for echo gas (C₃F₈) encapsulation (EGE) in nonionic solution such as 5% glucose. On the other hand, we were able to prepare bubble lipopolyplexes by inserting phosphate-buffered saline before C₃F₈ encapsulation. Surface charge regulation (SCR) by electrolytes stabilizes liposome/plasmid DNA (pDNA) complexes by accelerated membrane fusion. Considering these facts, we hypothesized that SCR by electrolytes such as NaCl would promote C₃F₈ encapsulation in bubble lipopolyplexes mediated by accelerated membrane fusion. We defined this hypothesis as SCR-based EGE (SCR-EGE). Bubble lipopolyplexes prepared by the SCR-EGE method (SCR-EGE bubble lipopolyplexes) are expected to facilitate the gene transfection because of the high amount of C₃F₈. Therefore, we applied these methods for gene delivery to the brain and evaluated the characteristics of transgene expression in the brain.
Methods: First, we measured the encapsulation efficiency of C₃F₈ in SCR-EGE bubble lipopolyplexes. Next, we applied these bubble lipopolyplexes to the mouse brain; then, we evaluated the transfection efficiency. Furthermore, three-dimensional transgene distribution was observed using multicolor deep imaging.
Results: SCR-EGE bubble lipopolyplexes had a higher C₃F₈ content than conventional bubble lipopolyplexes. In terms of safety, SCR-EGE bubble lipopolyplexes possessed an anionic potential and showed no aggregation with erythrocytes. After applying SCR-EGE bubble lipopolyplexes to the brain, high transgene expression was observed by combining with ultrasound irradiation. As a result, transgene expression mediated by SCR-EGE bubble lipopolyplexes was observed mainly on blood vessels and partially outside of blood vessels.
Conclusion: The SCR-EGE method may promote C₃F₈ encapsulation in bubble lipopolyplexes, and SCR-EGE bubble lipopolyplexes may be potent carriers for efficient and safe gene transfection in the brain, especially to the blood vessels.