| Summary: | 碩士 === 國立中正大學 === 化學暨生物化學研究所 === 101 === Gene therapy is a technique that applies genes to treat or prevent diseases by delivering a gene into a patient’s cells. Over the past few years a considerable number of studies have been made on cyclodextrins (CDs) as drug carriers. Cyclodextrins are cyclic oligosaccharides composed of α-1, 4-coupled D-glucose units, which contain a hydrophobic internal cavity and hydrophilic outer surface. CDs are biocompatible and have low toxicities in animals and humans. Because of these unique physicochemical properties of CDs, CDs have often been used to design a novel pharmaceutical delivery system. In this study, the DNA/PEI25k nanoparticles with cyclodextrins（HP-α-CD, HP-β-CD, HP-γ-CD, Methyl-β-CD）were prepared to form inclusion complexes. The effects of CDs on the transfection efficiency of DNA/PEI25k particles and DNA/PLI600 particles were discussed. In addition, α-amylase（sourced from Aspergillus oryzae） showed a capability to degrade cyclodextrin. Therefore, we use α-amylase to degrade CDs and examined the release of DNA/PEI25k particles from inclusion complexes. Also, acetaminophen（APAP）and sulfamethazine（SMT）were used to help the release of DNA/PEI25k particles from CDs. The results reveal that, α-amylase catalyzes the hydrolysis of the α-1, 4 glycoside bond, but no change in transfection efficiency of DNA/PEI25k/CD inclusion complexes was observed. This is because, in presence of amylase, significantly large and negatively charged particles were formed. However, in presence of APAP or SMT, the transfection efficiency of the DNA/PEI25k particles was popped to show an increase from 0.34 to 1.1 or 1.28, respectively. In sumary, those results suggest that APAP or SMT could help the release of DNA/PEI25k particles from cyclodextrins in vitro.
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