Proof-of-Concept of Electrical Activation of Liposome Nanocarriers: From Dry to Wet Experiments.

Laura Caramazza,Francesca Apollonio,Patrizia Paolicelli,Martina Nardoni,Stefania Petralito,Micaela Liberti,Annalisa De Angelis

doi:10.3389/fbioe.2020.00819

Abstract

The increasing interest toward biocompatible nanotechnologies in medicine, combined with electric fields stimulation, is leading to the development of electro-sensitive smart systems for drug delivery applications. To this regard, recently the use of pulsed electric fields to trigger release across phospholipid membranes of liposomes has been numerically studied, for a deeper understanding of the phenomena at the molecular scale. Aim of this work is to give an experimental validation of the feasibility to control the release from liposome vesicles, using nanosecond pulsed electric fields characterized by a 10 ns duration and intensity in the order of MV/m. The results are supported by multiphysics simulations which consider the coupling of three physics (electromagnetics, thermal and pore kinetics) in order to explain the occurring physical interactions at the microscopic level and provide useful information on the characteristics of the train of pulses needed to obtain quantitative results in terms of liposome electropermeabilization. Finally, a complete characterization of the exposure system is also provided to support the reliability and validity of the study.

Highlights

In the last few decades, there has been great interest in developing drug delivery systems involving the use of liposomal nanodevices carriers, as promising tools either for treatment of cancer diseases (Rosenblum et al, 2018; Senapati et al, 2018; Riley et al, 2019) or for non-cancer ones such as cardiovascular, neurological and autoimmune disorders, respiratory system diseases, skin illness (Bayat et al, 2020; Moncalvo et al, 2020)
This last characteristic is promising in the evolution of liposome technology, because one can think of electromagnetic fields as actuators; in practice it will allow engineers to design a rational and remote control of the release making liposome vesicles a reservoir of the drug or molecule to be released on site and on-demand
According to the established experimental protocol, the release profile of the 5-(6) CF dye was studied after the nanosecond pulsed electric fields (nsPEFs) stimulation of the sample and the results were compared with the related controls, with no electrical signal application

Summary

Introduction

In the last few decades, there has been great interest in developing drug delivery systems involving the use of liposomal nanodevices carriers, as promising tools either for treatment of cancer diseases (Rosenblum et al, 2018; Senapati et al, 2018; Riley et al, 2019) or for non-cancer ones such as cardiovascular, neurological and autoimmune disorders, respiratory system diseases, skin illness (Bayat et al, 2020; Moncalvo et al, 2020). The novel generation of lipid vesicles is based on: (i) functionalized nsPEFs Activation of Liposome Vesicles surface to reach the selected cell or tissue – ligand targeted liposomes – (Daeihamed et al, 2017), (ii) deformed and elastic structure in order to be administered via transdermal and oral routes – transfersome – (Bayat et al, 2020), and (iii) ability to be triggered by an external or internal stimulus such as pH, temperature, redox potential, enzymes, electrolyte concentration and even magnetic fields to achieve a spatiotemporal control of drug release – smart delivery system – (Murdan, 2003; Spera et al, 2014, 2015; Kim and Lee, 2017; Nardoni et al, 2018; Liu and An, 2019; Yuba, 2020) This last characteristic is promising in the evolution of liposome technology, because one can think of electromagnetic fields as actuators; in practice it will allow engineers to design a rational and remote control of the release making liposome vesicles a reservoir of the drug or molecule to be released on site and on-demand

Objectives

Methods

Results

Conclusion