Substituted beta-cyclodextrins interact with PAMAM dendrimer-DNA complexesand 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 d endrimer/DNA/beta -CD formulations were applied on the surface of collagen membranes. The inclusion of beta -CD into the formulations resulted in part icles that were smaller and more evenly distributed on the surface of the s olid support. The average size of the complex formed at 50 mug/ml anal at c harge 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 increase d concentration may displace DNA in the dendrimer/DNA complex. High concent rations of amphoteric beta -CD do not dissociate dendrimer/DNA complexes; h owever, they may decrease their ability to transfect cells. At the optimize d formulations the surface-modified beta -CDs may enhance solid support-bas ed transfection in vitro, through modification of dendrimer/DNA complex com position and improved surface distribution. (C) 2001 Academic Press.