Lipoprotein-resembling submicron emulsion for drug and gene delivery
Shawer, Mohannad Mahmoud
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Several anticancer compounds that have shown excellent efficacy are known to have high incidence of toxicity. The main reason of such toxicity can be due to lack of targeting ability of the drug in the body where in doesn’t discriminate between normal and cancer cells. The main focus of this research is to create a new-targeted drug/gene delivery system.|Low-density lipoprotein, LDL is known to carry cholesterol in the body and deliver it to cells via receptor- mediated endocytosis. Elevated LDL-receptor activity was reported in several cancer cells. Consequently, LDL has been identified as a potential drug carrier system for anticancer drug targeting to benefit from preferential delivery into cancer cells.|Due to the practical problems associated with loading drugs into LDL, we investigated the possibility of creating a surrogate system that resembles the native lipoproteins in its chemical and physical properties. We incorporated a cholesterol-based compound, BCH, in lipoprotein-resembling submicron emulsion and studied the physical properties of the formulation as well the drug uptake into cancer cells (9 L rat glioma, and SF-767 human glioblastoma multiforme).|The second component of the artificial lipoprotein system is a hydrophobized protein/polymer that will associate at the surface of the submicron emulsion. We investigated the ability of hydrophobized polylysine to associate with the emulsion particles and the ability of this polymer/lipid system to carry DNA.|Different targeting molecules can be associated with these emulsion particles to target different tissues depending on the hydrophobized protein/polymer used. We described a detailed method to carry protein hydrophobization with minimal denaturation of the protein.|In conclusion were we able to formulate a lipoprotein-resembling submicron emulsion. We’ve shown the ability of this system to solubilize water insoluble compound and to deliver the drug to cancer cells. We’ve also shown the potential application of the artificial lipoprotein system in gene delivery.