Special Event: Seminar

Lipid Membrane Heterogeneities Controlled By PH:
Applications In Liposome-based Drug Delivery



May 6th, 2008
10 AM
Mudd 826

Stavroula Sofou, Ph.D.
Othmer-Jacobs Department of Chemical and Biological Engineering
Brooklyn, NY

Nature uses lipid membranes as a universal wrap around cells to control critical functions by reorganizing them into heterogeneous lipid domains. These domains consist of laterally phase separated lipids and their occurrence coincides with locally confined and clustered membrane proteins and other macromolecules on the surface of cells. These membrane heterogeneities are of particular interest given their role in biological phenomena including membrane trafficking, signaling, and protein transport. We study the formation of model lipid heterogeneities tuned by pH on vesicle membranes with a dual aim. First, we evaluate their effect on surface patterning that may induce changes in local multivalency and binding efficacy of attached ligands. Second, we characterize the structure of interfacial boundaries among the separated lipid phases, and we demonstrate their role on altering the bilayer permeability and on promoting intermembrane fusion.

Using our findings we design PEGylated liposomes as drug carriers composed of membranes with pH-tunable lipid heterogeneities and with cancer targeting ligands on their surface to enable triggered binding and content release. We use these properties to engineer liposomes that hide the targeting ligands from their surface during circulation in the blood, and only expose and cluster the targeting ligands on their surface after localization of liposomes within the tumor interstitium to increase specific targeting and reduce normal organ uptake. In addition, we develop liposomes that quickly release their encapsulated therapeutic contents after endocytosis by forming leaky interfacial boundaries among separated lipid phases to increase the bioavailability of delivered therapeutics.Disseminated vascularized tumors still account for the majority of cancer mortality.These PEGylated vesicles with long blood circulation times, tunable specific binding and pH-controlled release of contents could become potent drug delivery carriers for the targeted therapy of solid tumors.

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