Substituted beta-cyclodextrins interact with PAMAM dendrimer-DNA complexes and modify transfection efficiency.

The efficiency of PAMAM dendrimer-mediated DNA transfer can be improved by the addition of substituted beta-cyclodextrins (beta-CDs) as formulation excipients. In vitro CAT expression increased approximately 200-fold when dendrimer/DNA/beta-CD formulations were applied on the surface of collagen membranes. The inclusion of beta-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 microg/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 beta-CDs. Sulfonated beta-CDs bind to dendrimer and in the increased concentration may displace DNA in the dendrimer/DNA complex. High concentrations of amphoteric beta-CD do not dissociate dendrimer/DNA complexes; however, they may decrease their ability to transfect cells. At the optimized formulations the surface-modified beta-CDs may enhance solid support-based transfection in vitro, through modification of dendrimer/DNA complex composition and improved surface distribution. Copyright 2001 Academic Press.