Fabrication of a Charge-Conversion Polymer—Liposome for Enhancing Endosomal Escape of Drug Delivery System for α–Mangostin

Abstract

α–Mangostin, which is a natural xanthone compound, inhibits the metastasis and survival of various cancer cell types. However, its therapeutic effectiveness is limited by low water solubility and very poor absorption. There are several studies that developed the drug delivery system for α–mangostin, but they are still a remaining challenge. Drug delivery techniques are severely hampered by the breakdown of nanoparticles inside endosomes. The abrasive chemical environment in these compartments causes both the nanoparticles and the encapsulated α–mangostin to degrade throughout the course of the voyage. Intracellular defenses against external materials refer to this collective mechanism. A pH-responsive liposome named PAsp(DET-Cit)–Toc, made of lipids and a charge-conversion polymer (CCP), has been created for the targeted transport of α–mangostin in order to avoid this deteriorative outcome. The average hydrodynamic size of CCP–liposome particles is 98.59 ± 5.1 nm with a PDI of 0.098 ± 0.02 and a negative zeta potential of 22.31 ± 2.4 mV. TEM showed the shape of the spherical CCP–liposomes. α–Mangostin is successfully captured inside CCP–liposome and the loading yield reached the highest encapsulation efficiency of 83% with 150 μg/mL of α–mangostin. In the acidic condition of pH 5.0, an initial burst of α–mangostin reached 50% after 6 h in buffer solution. CCP–liposomes could escape from endosomes even after 3 h, and almost 80% of CCP–liposomes escaped after 24 h. The cell ability of α–mangostin-loaded-CCP–liposome incubated in buffer solutions of 5.0 decreased significantly and was close to free α–mangostin. Our data proved that α–mangostin-loaded CCP–liposome delivered more effectively α–mangostin into cells and prevented the degradation of α–mangostin inside cells, especially endosomal degradation.