Preparation of albumin-targeted liposomes and the study of their release characteristics using ultrasound

Abstract

The main objective of this thesis was to investigate the enhancement of drug delivery using targeted liposomes triggered by ultrasound. In this thesis, a thorough literature review on cancer and drug delivery systems (especially liposomes) was conducted. An overview of nanoparticles as drug delivery carriers, different types of drug targeting and the use of ultrasound to control drug release from nanocarriers is also reported. In the study, albumin-targeted liposomes (proteoliposomes) were prepared and loaded with the model drug calcein. The release studies were performed using different ultrasound power densities at 20-kHz. The size of both liposomes types was determined by Dynamic Light Scattering. The release experiments were done online, by continuously measuring the increase in fluorescence when the calcein self-quenching was relieved upon release. The 20-kHz ultrasound was applied in 20 s pulses with a 10 s inter-pulse interval. In the end, total release was determined by lysing the remaining liposomes with Triton X-100. The prepared liposomes were large unilamellar vesicles with diameters 208.52±11.50 nm (non-targeted control liposomes) and 218.27±12.73 nm (albumin liposomes). Although albumin liposomes are larger, the difference was not significant. For both liposome types, the 20-kHz ultrasound-induced release was fast, reaching a stable value after 150 - 250 s. The release rate increased with increasing power densities, and the final percentage of release was higher than 90% for all power densities. For the same power density, the release from non-targeted liposomes was significantly faster than for albumin liposomes, which suggests that the addition of the albumin moiety changes the acoustic properties of the liposomes, apparently increasing their stability and making them less susceptible to ultrasound. The findings allowed us to conclude that these liposomes could be promising nanocarriers for the anti-cancer drug doxorubicin, enhancing the therapeutic efficacy of the drug and decreasing the side effects of the common chemotherapy cancer treatment.