The Effects of cRGD Targeting Liposomes When Paired With Ultrasonic Waves on Drug Delivery

Abstract

Cancer is a leading fatal disease, which has the ability to grow uncontrollably and spread throughout the body of the patient. Several approaches have been used to treat cancer, chemotherapy being the most common treatment method. Accompanying this therapy are several drawbacks that have detrimental effects on the patient both physiologically and psychologically. Those effects include hair loss, infection, anemia, in addition to congestive heart failure. New remedies have been introduced to mitigate the undesired side effects of chemotherapy, such as the Novel Drug Delivery Systems (NDDSs). This relatively new technique is an approach that carries the cytotoxic drugs through the blood to the precise tumor site through vesicular structures. Those structures then accumulate at the tumor site and deliver their chemotherapeutic cargo. To induce further effective drug delivery, a moiety is added to the surface of liposomal nanoparticles, in this thesis, the cyclic-RGD sequence. This tripeptide sequence, in turn, actively targets cRGD receptors overexpressed on the surface of cancer cells. Upon binding to the receptor, these targeted liposomes are taken up by the cells through receptor-mediated endocytosis. Ultrasonic waves are then applied to release the liposomal contents in a timely manner. Using DLS, the radii were measured at 84.98 nm and 99.36 for control and cRGD liposomes, respectively. Protein attachment was validated using quantification protocols, which yielded higher protein ratios of 4.5383. 3.1875, and 2.5545 in cRGD liposomes compared to the control. The LFUS release was studied at 6.2, 9, and 10 mW/cm² power intensity with a frequency of 20kHz for 20 secs ON and 20 secs OFF. It was concluded that higher intensities instigated fewer pulses and achieved the rapid release of calcein, a model drug, from liposomes. The zero-order, Higuchi, Korsmeyer-Pappas, and Weibull models were the best fitting kinetic models for the experimental data. By combining biological targeting (via receptor-moiety binding) and an external stimulus (i.e., ultrasound), this thesis shows the promise of targeted drug delivery platforms.