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.
Roessler
B J
BJ
Department of Internal Medicine and Center for Biologic Nanotechnology, University of Michigan, Ann Arbor 48109, USA. roessler@med.umich.edu
Bielinska
A U
AU
Janczak
K
K
Lee
I
I
Baker
J R
JR
D000818:Animals; D019556:COS Cells; D002626:Chemistry, Pharmaceutical; D020099:Coated Materials, Biocompatible / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003198:Computer Simulation; D003505:Cyclodextrins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D050091:Dendrimers; D005079:Excipients / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter / Q000235:genetics; D008027:Light; D046911:Macromolecular Substances; D008567:Membranes, Artificial; D008958:Models, Molecular; D010316:Particle Size; D010715:Phosphatidylglycerols / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism*; D012542:Scattering, Radiation; D014162:Transfection / Q000379:methods*; D047392:beta-Cyclodextrins
D020099:Coated Materials, Biocompatible; D003505:Cyclodextrins; D050091:Dendrimers; D005079:Excipients; D046911:Macromolecular Substances; D008567:Membranes, Artificial; C104700:PAMAM Starburst; D010715:Phosphatidylglycerols; D011073:Polyamines; D047392:beta-Cyclodextrins; D003094:Collagen; D004247:DNA; C031215:betadex