Assessing liposomal nanocarriers for targeted drug delivery through electroporation

Electroporation (EP) is a technique that temporarily increases cell membrane permeability through high-voltage electrical pulses, facilitating the internalization of hydrophilic drugs. When used in clinics, reversible EP offers significant advantages in drug delivery with minimal systemic toxicity, making it a promising approach in cancer therapy (Electrochemotherapy). However, is still challenging to increase therapeutic efficacy, such as increasing the amount of drug internalized by cells after EP. To address these limitations, integrating nanocarriers-particularly liposomes-into EP-based drug delivery strategies has shown great promise. Due to their structural similarity to cell membranes, liposomes can undergo electroporation without causing irreversible cell damage, enabling localized and controlled drug release at targeted sites. This study preliminary evaluates the effectiveness of positively charged gentamicin sulfate loaded liposomes (GS-Lipo) in enhancing gentamicin sulfate uptake through electroporation. The focus is on liposome behavior under EP, drug release, and cellular internalization. The results reveal a strong interplay between liposomes and EP. While EP minimally affects liposome size (sizes lower than 250 nm before and after EP) and PDI, it significantly enhances intracellular uptake and drug release by creating transient pores in liposomal bilayer, facilitating gentamicin diffusion. In vitro uptake studies performed with fluorescent liposomes and GS-Lipo, confirmed superior performance when combined treatment (EP + GS-Lipo) is used. By optimizing electroporation parameters (160 V, 200 V, and 250 V), this study succeeds in maximizing intracellular drug concentration, with the long-term goal of improving therapeutic outcomes, particularly in cancer treatment.