| Abstract
| - Cationic polymers show promise for the in vitro and in vivo delivery of macromolecular therapeutics.Known cationic polymers, e.g., poly(L)lysine (PLL) and polyethylenimine (PEI), have been employedin native and modified forms for the delivery of plasmid DNA (pDNA) and reveal varying levels oftoxicity. Here, we report the preparation of a new class of cationic polymers that are specificallydesigned to deliver macromolecular therapeutics. Linear, cationic, β-cyclodextrin (β-CD)-containingpolymers (CD-polymers) are synthesized by copolymerizing difunctionalized β-CD monomers (AA) withother difunctionalized comonomers (BB) such that an AABBAABB product is formed. The β-CDpolymers are able to bind ∼5 kbp pDNA above polymer to DNA (+/−) charge ratios of 1.5, compactthe bound pDNA into particles of approximately 100−150 nm in size at charge ratios above 5+/−,and transfect cultured cells at charge ratios above 10+/−. In vitro transfections with the new β-CD-polymers are comparable to the best results obtained in our hands with PEI and Lipofectamine. Somecell line-dependent toxicities are observed for serum-free transfections; however, no toxicity is revealedat charge ratios as high as 70+/− in transfections conducted in 10% serum. Single IV and IP doses ashigh as 200 mg/kg in mice showed no mortalities.
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