Study of the Dynamic Uptake of Free Drug and Nanostructures for Drug Delivery Based on Bioluminescence Measurements

Abstract

The past two decades have witnessed the great growth of the development of novel drug carriers. However, the releasing dynamics of drug from drug carriers in vivo and the interactions between cells and drug carriers remain unclear. In this paper, liposomes were prepared to encapsulate D-luciferin, which was the substrate of luciferase and served as a model drug. Based on the theoretical calculation of active loading, methods of preparation for liposomes were optimized. Only when D-luciferin was released from liposomes or taken in by the cells could bioluminescence be produced under the catalysis of luciferase. Models of multicellular tumor spheroid (MCTS) were built with 4T1-luc cells that expressed luciferase stably. The kinetic processes of uptake and distribution of free drugs and liposomal drugs were determined with models of cell suspension, monolayer cells, MCTS, and tumor-bearing nude mice. The technology platform has been demonstrated to be effective for the study of the distribution and kinetic profiles of various liposomes as drug delivery systems.