Safety Assessment
Marie Ojiambo

Electroporation as a Drug Delivery System for COVID-19 Vaccines

This drug and vaccine delivery system relies on electrical pulses to help stimulate immune responses

Common vaccine platforms including viral vectors and live/attenuated/inactivated virus vaccines have been the talk of the town since the SARS-Cov-2 pandemic. As the race for a vaccine took off, innovators began looking for better, more efficacious drug delivery systems. Some of these drug delivery systems include cutting- edge medical devices that are now in use for other vaccines. One such in vivo drug delivery technology is electroporation (EP).

Electroporation is a delivery method that is used to introduce macromolecules such as proteins into cells, either in vivo or in vitro, via the application of brief electric pulses which induce momentary and reversible permeabilization of the cell membrane. This allows these macromolecules to move into the cells. For drugs that are small molecules, entry of these molecules into the cells happens across the cell membrane via simple diffusion. Nucleic acid, nucleotides and/or DNA are too large to enter through the hydrophilic pores—polar transmembrane pores—by simple diffusion. DNA and nucleotides are polyanions, containing an overabundance of negative charges, enabling these molecules to move in an electric field. However, moving these molecules is not sufficient; in addition to this, the cell membrane needs to be in a permeabilized state in order to allow successful passage of DNA and nucleotide molecules. EP devices are thus indicated to enhance the uptake and expression of DNA plasmid-based biologics in order to enhance protein drug delivery and efficacy.

It’s Electric!

Electroporation has been shown to have a significant impact on vaccine immunogenicity and efficacy. This is because it has the potential to increase antigen delivery as much as a 1000-fold over naked DNA delivery technologies alone. This increased delivery translates to an improved immune response magnitude as well as improved response rates relative to DNA delivery by direct injection alone.

Electroporation is accomplished through a sterile, disposable needle array attached to an applicator. The DNA plasmid of interest is delivered separately via intradermal or intramuscular needle injection to an area marked by the electrodes immediately prior to the electroporation treatment. The electroporation treatment is achieved by introducing an electrical pulse/s of defined magnitude and length to the cells of interest.

The voltage causes a brief period of cell membrane destabilization and the macromolecules that are injected into the extracellular medium surrounding these target cells gain access to the intracellular milieu of the cells. DNA molecules can translocate across the cell membrane pores during this period of membrane destabilization.

It is noteworthy that simple diffusion will continue to take place across the cell as long as the cell membrane is permeabilized, i.e. before and even several minutes after the pulses have been given. However, DNA must be added to the site of electroporation prior to the application of an electric pulse, in order to be subjected to the electrophoretic effect necessary to transfer the DNA across the cell membrane. It has been shown that when DNA is added after the pulses, but while the cell is still permeabilized, there is no transfection.

The permeabilization structures will start to form in a matter of microseconds during the first pulse and will reseal in the order of minutes after pulses have ended. A number of pulses from 1-7 are delivered per session depending on the route (Intramuscular or subcutaneous) and voltage used.

Gene electro transfer via electroporation technology has been shown to be well-tolerated. It is performed very quickly, and the amount of discomfort is tolerable.