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

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.

Identiferoai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2327
Date15 May 2009
CreatorsChern, Christina
ContributorsHahn, Mariah
Source SetsTexas A and M University
Languageen_US
Detected LanguageEnglish
TypeBook, Thesis, Electronic Thesis, text
Formatelectronic, application/pdf, born digital

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