Liposomal cargo unloading induced by pH sensitive peptides and probing peptide self -replication within liposomes
Abstract
Programmed release of liposomal contents is one of the crucial step in the liposomal drug delivery process. This work describes amphiphilic peptides designed to have a pH-dependent conformational change and lipid binding. At physiological pH, the peptides would exist in random coil conformation, but at endosomal pH they would switch to amphiphilic α-helices, disrupt membranes, and release liposomal contents. A series of peptides has been investigated that contains a high percentage of Glu residues for the pH conformation switch, and Leu residues for optimal lipid binding. pH-dependent CD results will be described, along with liposomal release data at neutral and acidic pH, to document the success of the design strategy. The peptides have also been encapsulated into propidium iodide (PI) containing, folate-conjugated liposomes and incubated with KB cells to study the effect of the peptides on liposomal content release. Cellular fluorescence due to the successful delivery of PI will be discussed. We also successfully demonstrated the feasibility to have self-replication reactions inside liposomes to mimic protocell. Initial rate study of the product formation in liposomes overall has shown faster reaction rate then in the aqueous environment. To obtain rate constants using the Simfit fitting method, a chemically inert lipid and internal standard may be needed.
Degree
Ph.D.
Advisors
Chmielewski, Purdue University.
Subject Area
Organic chemistry|Pharmaceuticals
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