PMID: 11312690Apr 21, 2001Paper

Effects of structure of beta-cyclodextrin-containing polymers on gene delivery

Bioconjugate Chemistry
S J HwangM E Davis

Abstract

Linear cationic beta-cyclodextrin-based polymers (betaCDPs) are capable of forming polyplexes with nucleic acids and transfecting cultured cells. The betaCDPs 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 betaCDPs 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 (betaCDP4, 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 betaCDP6 polymer. In vitro toxicity varied by 1 order of magnitude and the lowest toxicity is observed with betaCDP8. The LD40 of the betaCDP6 to mice is 200 mg/kg, making this polymer a promising agent for in vivo gene delivery applications.

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Citations

Apr 7, 2004·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Sally-Ann CryanCaitriona M O'Driscoll
Apr 16, 2002·Current Opinion in Biotechnology·Mark E Davis
Dec 2, 2004·Nature Reviews. Drug Discovery·Mark E Davis, Marcus E Brewster
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May 18, 2013·Advanced Drug Delivery Reviews·Koen RaemdonckStefaan C De Smedt
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Dec 1, 2013·Drug Delivery and Translational Research·Rajan SwamiSistla Ramakrishna
Apr 23, 2009·Expert Opinion on Drug Delivery·Chao Lin, Johan F J Engbersen
Sep 5, 2006·Expert Opinion on Drug Delivery·Jeremy D Heidel
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Oct 10, 2013·Biomaterials·Wing-Fu Lai
Apr 1, 2017·Therapeutic Delivery·Palpandi PandiWahid Khan

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