Ultrasound triggered drug delivery of transferrin coupled liposomes carrying the drug doxorubicin

Abstract

Cancer is one of the deadliest diseases of the 21st century. It is caused by the uncontrolled division of damaged and mutated cells. Several methods have been developed to combat cancer, including surgery, radiation, and chemotherapy. However, due to the nature of the disease and the cytotoxicity of the treatments, these treatments' effectiveness is limited. To mitigate the cytotoxicity of these treatments and improve efficacy, Smart Drug Delivery Systems are studied. These delivery systems contain nanoparticle that encapsulates a chemotherapeutic drug and delivers it selectively to the tumor site. This work will utilize a PEGylated liposome coupled with the protein Transferrin encapsulating the chemotherapeutic drug Doxorubicin. The PEG protects the vesicles from the human body's immune system. The vesicle can passively target the tumor site. Moreover, the transferrin ligand selectively binds to cancer cells, improving uptake chances. The liposomes were synthesized using the film hydration method. The averaged size of the control liposomes and Transferrin-targeted liposomes are 85.2 ± 5.83 nm, and 85.3 ± 7.15 nm, respectively. The lipid content of the liposomes is quantified, and the result for control liposomes is 8.024 ± 0.126 mg/ml, while the result for the Tf-targeted liposomes is 6.219 ± 1.109 mg/ml using the Stewart Assay. The conjugation of Transferrin proven using the BCA assay as the protein content was 2-fold higher than the control liposomes. Low-frequency ultrasound release is conducted using a 20-kHz US probe at three power densities, namely, 7.46, 9.85, 17.31 mW/cm2, and the results showed an increase in the release of Doxorubicin from the transferrin coupled liposomes. The release results are fitted to nine different models, and the best-fitting model is the zero-order model. The second and third best-fitting models are Hixson-Crowell and Hopfenberg. Using three modalities of drug delivery targeting (passive, ligand, and acoustic triggered) may aid in curbing the unwanted side effects of conventional chemotherapy.