Formulation and evaluation of an artificial lipoprotein gene delivery system for targeted gene delivery to glioma cells ; effect of dual surfactant systems on properties of ethyl cellulose microspheres prepared by non-aqueous emulsion-solvent evaporation
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In the first part of the dissertation, the formulation and development of an artificial lipoprotein gene delivery system is discussed. Cancer cells have a higher requirement for cholesterol than normal cells since they are growing at a faster rate and have over-expressed LDL receptors. This difference can be used to selectively target cancer cells. Apolipoprotein B-100 is the ligand recognized by the LDL receptors and an artificial lipoprotein, composed of a lipid nanoemulsion having Apolipoprotein B-100 on its surface, can be used for targeted gene delivery to cancer cells. Apolipoprotein B-100 was conjugated to the lipid nanoemulsion and the gene delivery complexes were assembled by incubating the artificial lipoprotein, modified poly-L-lysine and reporter gene at various ratios. The transfection efficiency of the complexes were determined in human glioma cell line SF-767. It was observed that the artificial lipoprotein with Apolipoprotein B-100 had better transfection efficiency than nanoemulsion (without TMApolipoprotein B-100) and commercial reagent Lipofectamine because of the presence of Apolipoprotein B-100. In the second part of the dissertation, the effect of dual surfactant systems on the physical and drug release properties of ethylcellulose microspheres prepared by non-aqueous emulsion-solvent evaporation method was studied. Specifically, the effect of RHLB and surfactant type was investigated. Low and high HLB surfactants can be combined in different ratios to obtain intermediate HLBs (called RHLB). Different batches of microspheres were made at different RHLBs by combining two low HLB surfactants (Span 80, Arlacel 83 and Span 85) and two high HLB surfactants (Tween 61 and Brij 30) in different ratios. The geometric mean diameter of the batches decreased with an increase in RHLB. The dissolution rate and dose dumping in the microsphere batches increased with an increase in RHLB. . The dissolution rate and initial drug release is less in batches made with Span 80 than Span 85 and Arlacel 83 indicating that the number of chains in the surfactant structure is important in determining the drug release characteristics. The type of linkage in Brij 30 and Tween 61 also seems to influence the release characteristics.