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SPECIFIC DRUG DELIVERY In recent studies, peptides amphiphiles have been shown to be a potential tool for specific drug delivery. Our peptide amphiphile is composed of a hydrophobic tail and a peptide head group. The tail is the hydrophobic part made of two saturated alkyl chains, which promotes inclusion into the lipid membrane of the liposomes. The head group is attached to the tails with a glutanic acid linker and a C2 spacer. The head is derived from a region of type IV collagen that is known to bind to melanoma. The ability of the peptide amphiphile to specifically bind cells along with their amphiphilic character make them a very good candidate for drug delivery in liposomes (see fig. 1). Liposomes, which are characterized by their spherical geometry and their lipid bi-layers, are able to encapsulate hydrophilic as well as lipophilic molecules. In order to develop a better synthetic peptide amphiphile targeted vesicle, we propose to study the effectiveness of various compositions on vesicles formation. The success of vesicle formation depends on distinct factors such as concentration of DMPC, DMPE, PEG and concentrations of peptide amphiphile, temperature and time. Our goal is to obtain the specific data to optimize the best possible self-assembled structure. A structure that will not allow the liposomes to aggregate to one to another and that will target the specific cell. We will be able to determine those data by conducting experiments at various mixtures of lipids, molecular weight of PEG and molecular weights of peptide amphiphile. In order to determine if the data obtained are satisfactory (formation of liposome and no aggregation), we will run dynamic light scattering to measure the hydrodynamic diameter of the liposomes formed. Then, we will load the liposome with Texas Red DHPE; concentration<0.1%, a fluorescent dye-lipid, to help show the outcome of the liposomes complexed with mouse fibroblast cells. Fig. 1: pictures a & c DIL images of the fibroblast cells (those express similar integrins as of melanoma cells). Picture b represents the fibroblast cells after addition of liposomes without the peptide amphiphile. We see through fluorescent that only few liposomes attached themselves to the fibroblast cells. Picture d shows a high concentration of the liposomes with the peptide amphiphile bind to the melanoma cells. Pictures made available by Raymond Tu. |
