title: Structural effects of carbohydrate-containing polycations on gene delivery. 3. Cyclodextrin type and functionalization.
abstract: Linear cationic beta-cyclodextrin (beta-CD)-based polymers can form polyplexes with plasmid DNA and transfect cultured cells. The effectiveness of the gene delivery and the cellular toxicity has been related to structural features in these polycations. Previous beta-CD polycations were prepared from the cocondensation of 6(A),6(D)-dideoxy-6(A),6(D)-diamino-beta-CD monomers with other difunctionalized monomers such as dimethyl suberimidate (DMS). Here, the type of CD and its functionalization are varied by synthesizing numerous 3(A),3(B)-dideoxy-3(A),3(B)-diamino-beta- and gamma-CD monomers. Both alkyl- and alkoxydiamines are prepared in order to vary the nature of the spacing between the CD and the primary amines in the monomers. These diamino-CD-monomers are polymerized with DMS to yield amidine-based polycations. The nature of the spacer between the CD-ring and the primary amines of each monomer is found to influence both molecular weight and polydispersity of the polycations. When these polycations are used to form polyplexes with plasmid DNA, longer alkyl regions between the CD and the charge centers in the polycation backbone increase transfection efficiency and toxicity in BHK-21 cells, while increasing hydrophilicity of the spacer (alkoxy versus alkyl) provides for lower toxicity. Further, gamma-CD-based polycations are shown to be less toxic than otherwise identical beta-CD-based polycations.
authors.affiliation: Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Popielarski
authors.forename: Swaroop
authors.initials: S
authors.lastname: Mishra
authors.forename: Mark E
authors.initials: ME
authors.lastname: Davis
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry* / Q000502:physiology* / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D008027:Light; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D000071228:Polyelectrolytes; D012542:Scattering, Radiation; D014162:Transfection
chemical_list: D003505:Cyclodextrins; D011073:Polyamines; D000071228:Polyelectrolytes