Passive and Active Loading of Liposomes for Localized Drug Delivery

Faculty Mentor Information

Dr. Daniel Fologea

Abstract

The success of traditional approaches to chemotherapy used for cancer treatment is greatly diminished by the cumulative toxicity originating in its systemic nature. To alleviate this problem, scientists proposed using carriers capable of delivering antineoplastic drugs to tumors in a non-active, protected state. Liposomes are the most promising carriers for drug delivery, capable of transporting the drug cargo to multiple locations in the human body while evading the immune response. The work presented here focuses on exploring passive and active methods for liposome loading with drug simulators. Passive loading of several dyes and active loading of acridine orange into liposomes by creating a transmembrane pH gradient is proven using microscopy and fluorescence spectroscopy. In addition, our experiments demonstrate that dye molecules acting as drug simulators may be loaded into liposomes post-preparation by simple diffusion through lysenin channels inserted into the spherical bilayer membrane, and that the membrane may be completely resealed by addition of specific ligands. In conclusion, our work demonstrates that water-soluble drugs can be efficiently loaded into liposomal carriers for drug delivery purposes, and that regulated pore-forming proteins may be used for controlled drug loading and unloading.

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Passive and Active Loading of Liposomes for Localized Drug Delivery

The success of traditional approaches to chemotherapy used for cancer treatment is greatly diminished by the cumulative toxicity originating in its systemic nature. To alleviate this problem, scientists proposed using carriers capable of delivering antineoplastic drugs to tumors in a non-active, protected state. Liposomes are the most promising carriers for drug delivery, capable of transporting the drug cargo to multiple locations in the human body while evading the immune response. The work presented here focuses on exploring passive and active methods for liposome loading with drug simulators. Passive loading of several dyes and active loading of acridine orange into liposomes by creating a transmembrane pH gradient is proven using microscopy and fluorescence spectroscopy. In addition, our experiments demonstrate that dye molecules acting as drug simulators may be loaded into liposomes post-preparation by simple diffusion through lysenin channels inserted into the spherical bilayer membrane, and that the membrane may be completely resealed by addition of specific ligands. In conclusion, our work demonstrates that water-soluble drugs can be efficiently loaded into liposomal carriers for drug delivery purposes, and that regulated pore-forming proteins may be used for controlled drug loading and unloading.