The investigation of controlled release microchips, nanoparticles, and sirna for gene therapy in tissue engineering applications

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2009-05-15

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The study of drug delivery for the treatment of illnesses and injuries is an important area of pharmaceutical technology. A relatively new area of drug delivery being explored is gene therapy, which utilizes the idea that genes can be used as an alternative treatment. The exploration of gene delivery brought major advancements in the treatment of cancers and tumors as well as many challenges. In this study, the challenges of maintaining a stable vehicle for delivery, delivering genes into the cells, and the efficacy of the gene delivery vehicle were explored. Seven co-polymers of 12% (w/v) poly (D, L-lactic glycolide) (PDLG) were used to find a biodegradable polymer composition as an implant that temporarily controls the delivery of the genes. Of the formulations tested, 65/35 DL 3A and 50/50 DLG 4A were observed to show degradation time frames that best fit our purposes. Also, nanoparticles have been used to aid in the targeting of drugs to desired cells in delivery. One drawback of using nanoparticles is the potential toxic side effects they might cause. Zinc oxide nanoparticles coated with poly (vinyl pyrrolidone) (PVP) used as drug carriers were observed to have an effect on cell viability in previous studies. The cytotoxic effects of ZnO nanoparticles and PVP have on NIH 3T3 mouse fibroblast cells were investigated to see if there is a direct correlation between the level of PVP and zinc nanoparticles to the amount of cell death. It was found that an increase in concentration of ZnO nanoparticles correlates to a decrease in viability of the cells. It was also noted that the method of cell death is likely to be apoptosis. To confirm the efficacy of gene therapy through transfection, the transfection of the serum response factor (SRF) gene plasmid DNA and short interfering RNA (siRNA) were investigated. The efficiency of the transfection method were tested for both twodimensional and three-dimensional transfection of the SRF plasmid and siRNA. Experiments with two-dimensional transfection of the SRF plasmid and siRNA were successful, and transfer of the gene in the three-dimensional environment was observed with promising results with the siRNA.

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