Effect of High-Frequency Ultrasound on Targeted Liposomes

Abstract

Delivering highly toxic drugs inside a safe carrier to tumors while achieving controlled and effective drug release at the targeted sites represents an attractive approach to enhance drug efficiency while reducing its undesirable side effects. Functionalization of highly biocompatible nanocarriers such as liposomes conjugated with targeting moieties enhances their ability to target specific cancer cells overexpressing the targeted receptors. Furthermore, upon their accumulation at the target site, high-frequency ultrasound (HFUS) can be used to stimulate the controlled release of the loaded drugs. Here, the US-mediated drug release from calcein-loaded non-pegylated, pegylated as well as targeted-pegylated liposomes modified with human serum albumin (HSA) and transferrin (Tf) was investigated. HFUS at two different frequencies (1 MHz and 3 MHz) was found to trigger calcein release, with higher release rates recorded at the lower frequency (i.e., 1 MHz) compared to the higher frequency (i.e., 3 MHz) despite a higher power density. Pegylation was found to enhance liposomal sensitivity to HFUS. In addition, targeted pegylated liposomes were more susceptible to HFUS than non-targeted pegylated (control) liposomes. These findings show that pegylation and targeting moieties directly influence liposomal sensitivity to HFUS. Therefore, combining targeted-pegylated liposomes with HFUS represents a promising controlled and effective drug delivery system.