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Substituted β-Cyclodextrins Interact with PAMAM Dendrimer–DNA Complexes and Modify Transfection Efficiency

https://doi.org/10.1006/bbrc.2001.4690Get rights and content

Abstract

The efficiency of PAMAM dendrimer-mediated DNA transfer can be improved by the addition of substituted β-cyclodextrins (β-CDs) as formulation excipients. In vitro CAT expression increased approximately 200-fold when dendrimer/DNA/β-CD formulations were applied on the surface of collagen membranes. The inclusion of β-CD into the formulations resulted in particles that were smaller and more evenly distributed on the surface of the solid support. The average size of the complex formed at 50 μg/ml and at charge ratio of 1 decreased from 156 nm to 5.8 nm and 21.2 nm in 0.025–0.1% w/vol β-CDs. Sulfonated β-CDs bind to dendrimer and in the increased concentration may displace DNA in the dendrimer/DNA complex. High concentrations of amphoteric β-CD do not dissociate dendrimer/DNA complexes; however, they may decrease their ability to transfect cells. At the optimized formulations the surface-modified β-CDs may enhance solid support-based transfection in vitro, through modification of dendrimer/DNA complex composition and improved surface distribution.

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