Effects of Structure of b-Cyclodextrin-Containing Polymers on Gene Delivery

• Published in: Bioconjugate chemistry Vol. 12; no. 2; pp. 280 - 290
• Main Authors: Hwang, Suzie J, Bellocq, Nathalie C, Davis, Mark E
• Format: Journal Article
• Language: English
• Published: 16.02.2001
• ISSN: 1043-1802
• DOI: 10.1021/bc0001084

Linear cationic *b-cyclodextrin-based polymers (*bCDPs) are capable of forming polyplexes with nucleic acids and transfecting cultured cells. The *bCDPs are synthesized by the condensation of a diamino-cyclodextrin monomer A with a diimidate comonomer B. In this paper, the effects of polymer structure on polyplex formation, in vitro transfection efficiency and toxicity are elucidated. By comparison of the *bCDPs to polyamidines lacking cyclodextrins, the inclusion of a cyclodextrin moiety in the comonomer A units reduces the IC50s of the polymer by up to 3 orders of magnitude. The spacing between the cationic amidine groups is also important. Different polymers with 4, 5, 6, 7, 8, and 10 methylene units (*bCDP4, 5, 6, 7, 8, and 10) in the comonomer B molecule are synthesized. Transfection efficiency is dependent on comonomer B length with up to 20-fold difference between polymers. Optimum transfection is achieved with the *bCDP6 polymer. In vitro toxicity varied by 1 order of magnitude and the lowest toxicity is observed with *bCDP8. The LD40 of the *bCDP6 to mice is 200 mg/kg, making this polymer a promising agent for in vivo gene delivery applications.